dataset_id
large_stringclasses
414 values
reaction_id
large_stringlengths
36
36
reaction_smiles
large_stringlengths
4
873
rxn_insight_reaction
large_stringlengths
19
1.07k
mapped_reaction_smiles
large_stringlengths
14
3.37k
reactant_smiles
large_stringlengths
1
581
product_smiles
large_stringlengths
1
433
reagent_smiles
large_stringclasses
634 values
catalyst_smiles
large_stringlengths
1
683
solvent_smiles
large_stringlengths
1
245
rxn_insight_class
large_stringclasses
11 values
rxn_insight_name
large_stringclasses
346 values
rxn_insight_tag
large_stringlengths
64
64
rxn_insight_tag2
large_stringlengths
64
64
rxn_insight_scaffold
large_stringlengths
5
288
rxn_insight_template
large_stringlengths
24
2.64k
yield_percent
float64
-0.8
90,205,160,000B
yield_measurements
large_stringlengths
2
864
temperature_value
float64
-230
30.1k
temperature_units
large_stringclasses
3 values
reaction_time_value
float64
0
4k
time_units
large_stringclasses
4 values
procedure_details
large_stringlengths
1
23.6k
reference
large_stringclasses
96 values
doi
large_stringclasses
19 values
functional_groups_reactants
large_stringlengths
3
716
functional_groups_products
large_stringlengths
3
539
participating_rings_reactants
large_stringlengths
5
293
participating_rings_products
large_stringlengths
5
271
all_rings_products
large_stringlengths
5
271
byproduct_smiles
large_stringclasses
176 values
agent_smiles
large_stringlengths
1
712
temperature_c
float64
-230
30.1k
reaction_time_hours
float64
0
2.16k
reaction_smiles_with_agents
large_stringlengths
4
882
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-1574d9bf016a423897aab51d9da5f3e8
COc1ccccc1[C@H]1O[C@H](CC(=O)O)C(=O)N(CC(C)(C)C)c2ccc(Cl)cc21>>COc1ccccc1[C@H]1O[C@H](CC(=O)[O-])C(=O)N(CC(C)(C)C)c2ccc(Cl)cc21
ClC=1C=CC2=C([C@H](O[C@@H](C(N2CC(C)(C)C)=O)CC(=O)O)C2=C(C=CC=C2)OC)C1.[OH-].[Na+]>>ClC=1C=CC2=C([C@H](O[C@@H](C(N2CC(C)(C)C)=O)CC(=O)[O-])C2=C(C=CC=C2)OC)C1.[Na+]
[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[C@H:9]1[O:10][C@H:11]([CH2:12][C:13](=[O:14])[OH:15])[C:16](=[O:17])[N:18]([CH2:19][C:20]([CH3:21])([CH3:22])[CH3:23])[c:24]2[cH:25][cH:26][c:27]([Cl:28])[cH:29][c:30]21>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][cH:7][c:8]1[C@H:9]1[O:10][C@H:11]([CH2:12][C:13](=[O:14])[O-:15...
COc1ccccc1[C@H]1O[C@H](CC(=O)O)C(=O)N(CC(C)(C)C)c2ccc(Cl)cc21
COc1ccccc1[C@H]1O[C@H](CC(=O)[O-])C(=O)N(CC(C)(C)C)c2ccc(Cl)cc21
null
null
CO
Oxidation
Carboxylic acid to carboxylate
af9382a4a3fca177895c8a400271aa22025197fc08b983f9d71150044c1e6777
b3097057beeca787f1d4960a7ee432572ee7aecad541233195b0dbbc0f674e9c
O=C1CO[C@H](c2ccccc2)c2ccccc2N1
[C:1]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:4]>>[C:1]-[C:2](-[O-;H0;D1:4])=[O;D1;H0:3]
null
[]
null
null
null
null
To a suspension of (3R,5S)-7-chloro-5-(2-methoxyphenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid (12 g) in methanol (200 ml) was added 1N aqueous sodium hydroxide (27.7 ml). After the acid was dissolved completely, the mixture was concentrated in vacuo. To the residue was added ethyl acetate...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
null
null
null
c1ccccc1.c1ccc2c(c1)COCC[NH]2
null
CO
null
null
COc1ccccc1[C@H]1O[C@H](CC(=O)O)C(=O)N(CC(C)(C)C)c2ccc(Cl)cc21>CO>COc1ccccc1[C@H]1O[C@H](CC(=O)[O-])C(=O)N(CC(C)(C)C)c2ccc(Cl)cc21
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-2c708472c83f40bf8ae9adf5f16de858
BrCc1ccccc1.COc1cc(O)ccc1Br>>COc1cc(OCc2ccccc2)ccc1Br
BrC1=C(C=C(C=C1)O)OC.C(C1=CC=CC=C1)Br.C([O-])([O-])=O.[K+].[K+]>>C(C1=CC=CC=C1)OC1=CC(=C(C=C1)Br)OC
Br[CH2:7][c:8]1[cH:9][cH:10][cH:11][cH:12][cH:13]1.[CH3:1][O:2][c:3]1[cH:4][c:5]([OH:6])[cH:14][cH:15][c:16]1[Br:17]>>[CH3:1][O:2][c:3]1[cH:4][c:5]([O:6][CH2:7][c:8]2[cH:9][cH:10][cH:11][cH:12][cH:13]2)[cH:14][cH:15][c:16]1[Br:17]
BrCc1ccccc1.COc1cc(O)ccc1Br
COc1cc(OCc2ccccc2)ccc1Br
null
null
CC(=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccc(COc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[OH;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[O;H0;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
null
[]
null
null
24
HOUR
A mixture of 4-bromo-3-methoxyphenol (21 g), benzyl bromide (13.5 ml), potassium carbonate (21.4 g) and acetone (200 ml) was stirred at room temperature for 24 h. The insoluble materials were removed by filtration and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1
HBr
CC(=O)C
null
24
BrCc1ccccc1.COc1cc(O)ccc1Br>CC(=O)C>COc1cc(OCc2ccccc2)ccc1Br
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-8a08d4d95931403fb13cf9932fe3b98e
COc1cc(OCc2ccccc2)ccc1C(=O)c1cc(Cl)ccc1N>>COc1cc(OCc2ccccc2)ccc1C(O)c1cc(Cl)ccc1N
NC1=C(C(=O)C2=C(C=C(C=C2)OCC2=CC=CC=C2)OC)C=C(C=C1)Cl.[BH4-].[Na+]>>NC1=C(C(C2=C(C=C(C=C2)OCC2=CC=CC=C2)OC)O)C=C(C=C1)Cl
[CH3:1][O:2][c:3]1[cH:4][c:5]([O:6][CH2:7][c:8]2[cH:9][cH:10][cH:11][cH:12][cH:13]2)[cH:14][cH:15][c:16]1[C:17](=[O:18])[c:19]1[cH:20][c:21]([Cl:22])[cH:23][cH:24][c:25]1[NH2:26]>>[CH3:1][O:2][c:3]1[cH:4][c:5]([O:6][CH2:7][c:8]2[cH:9][cH:10][cH:11][cH:12][cH:13]2)[cH:14][cH:15][c:16]1[CH:17]([OH:18])[c:19]1[cH:20][c:21...
COc1cc(OCc2ccccc2)ccc1C(=O)c1cc(Cl)ccc1N
COc1cc(OCc2ccccc2)ccc1C(O)c1cc(Cl)ccc1N
null
null
CO
Reduction
Reduction of ketone to secondary alcohol
02790ac194d8bf7ccb13d6247c59412024d87f77d2c906ef7804f021f57d5070
1bd3cd74b454139c0a0068ac0135836499926b274bff569df163210c6c944a89
c1ccc(COc2ccc(Cc3ccccc3)cc2)cc1
[O;H0;D1;+0:1]=[C;H0;D3;+0:2](-[c:3](:[c:4]):[c:5])-[c:6](:[c:7]):[c:8]>>[OH;D1;+0:1]-[CH;D3;+0:2](-[c:3](:[c:4]):[c:5])-[c:6](:[c:7]):[c:8]
94.5
[{"value": 94.5, "product": "NC1=C(C(C2=C(C=C(C=C2)OCC2=CC=CC=C2)OC)O)C=C(C=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
To a solution of 2-amino-4'-benzyloxy-5-chloro-2'-methoxybenzophenone (10 g) in methanol (100 ml) was added sodium borohydride (1.4 g). After being stirred for 24 h, the mixture was concentrated in vacuo. The residue was diluted with water (200 ml) and extracted with ethyl acetate (300 ml). The extract was washed with ...
10.6084/m9.figshare.5104873.v1
null
Ketone
Secondary alcohol
null
null
c1ccccc1.c1ccccc1.c1ccccc1
null
CO
null
24
COc1cc(OCc2ccccc2)ccc1C(=O)c1cc(Cl)ccc1N>CO>COc1cc(OCc2ccccc2)ccc1C(O)c1cc(Cl)ccc1N
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-b478747f94e9498ba6d526c52d811437
CC(C)(C)C=O.COc1cc(OCc2ccccc2)ccc1C(O)c1cc(Cl)ccc1N>>COc1cc(OCc2ccccc2)ccc1C(O)c1cc(Cl)ccc1NCC(C)(C)C
C(#N)[BH3-].[Na+].NC1=C(C(C2=C(C=C(C=C2)OCC2=CC=CC=C2)OC)O)C=C(C=C1)Cl.C(C(C)(C)C)=O.C(C)(=O)O>>C(C1=CC=CC=C1)OC1=CC(=C(C=C1)C(C1=C(C=CC(=C1)Cl)NCC(C)(C)C)O)OC
O=[CH:27][C:28]([CH3:29])([CH3:30])[CH3:31].[CH3:1][O:2][c:3]1[cH:4][c:5]([O:6][CH2:7][c:8]2[cH:9][cH:10][cH:11][cH:12][cH:13]2)[cH:14][cH:15][c:16]1[CH:17]([OH:18])[c:19]1[cH:20][c:21]([Cl:22])[cH:23][cH:24][c:25]1[NH2:26]>>[CH3:1][O:2][c:3]1[cH:4][c:5]([O:6][CH2:7][c:8]2[cH:9][cH:10][cH:11][cH:12][cH:13]2)[cH:14][cH:...
CC(C)(C)C=O.COc1cc(OCc2ccccc2)ccc1C(O)c1cc(Cl)ccc1N
COc1cc(OCc2ccccc2)ccc1C(O)c1cc(Cl)ccc1NCC(C)(C)C
null
null
C(C)O
Heteroatom Alkylation and Arylation
Reductive amination with aldehyde
422be648aea52bce28ccc8fb32ec3178aaa47bbd624f063874619362f075b5f2
7915721a3e395aed85e3c40dc4d725c571a931ac517c6a0da16f2a2b0bb5eac7
c1ccc(COc2ccc(Cc3ccccc3)cc2)cc1
O=[CH;D2;+0:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[C;D1;H3:5].[NH2;D1;+0:6]-[c:7](:[c:8]):[c:9]>>[C;D1;H3:3]-[C:2](-[C;D1;H3:4])(-[C;D1;H3:5])-[CH2;D2;+0:1]-[NH;D2;+0:6]-[c:7](:[c:8]):[c:9]
null
[]
null
null
30
MINUTE
A mixture of 2-amino-α-(4-benzyloxy-2-methoxyphenyl)-5-chlorobenzyl alcohol (9.5 g), pivalaldehyde (3.35 ml), acetic acid (1.85 g) and ethanol (200 ml) was stirred for 30 min. To the mixture was added sodium cyanoborohydride (2.33 g) and the mixture was stirred for 24 h. After the mixture was concentrated in vacuo, the...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Primary amine
Secondary amine
null
null
c1ccccc1.c1ccccc1.c1ccccc1
Other
C(C)O
null
0.5
CC(C)(C)C=O.COc1cc(OCc2ccccc2)ccc1C(O)c1cc(Cl)ccc1N>C(C)O>COc1cc(OCc2ccccc2)ccc1C(O)c1cc(Cl)ccc1NCC(C)(C)C
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-0bc1a7edcd584f338aa5705126d111be
CCOC(=O)C=CC(=O)N(CC(C)(C)C)c1ccc(Cl)cc1C(O)c1ccc(OCc2ccccc2)cc1OC>>CCOC(=O)C[C@H]1O[C@H](c2ccc(OCc3ccccc3)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O
ClC1=CC(=C(C=C1)N(C(=O)C=CC(=O)OCC)CC(C)(C)C)C(C1=C(C=C(C=C1)OCC1=CC=CC=C1)OC)O.C([O-])([O-])=O.[K+].[K+]>>C(C1=CC=CC=C1)OC1=CC(=C(C=C1)[C@H]1O[C@@H](C(N(C2=C1C=C(C=C2)Cl)CC(C)(C)C)=O)CC(=O)OCC)OC
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]=[CH:7][C:39]([N:33]([c:32]1[c:26]([CH:9]([OH:8])[c:10]2[cH:11][cH:12][c:13]([O:14][CH2:15][c:16]3[cH:17][cH:18][cH:19][cH:20][cH:21]3)[cH:22][c:23]2[O:24][CH3:25])[cH:27][c:28]([Cl:29])[cH:30][cH:31]1)[CH2:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:40]>>[CH3:1][CH2:2][O:3][C:4](=[O...
CCOC(=O)C=CC(=O)N(CC(C)(C)C)c1ccc(Cl)cc1C(O)c1ccc(OCc2ccccc2)cc1OC
CCOC(=O)C[C@H]1O[C@H](c2ccc(OCc3ccccc3)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O
null
null
C(C)O
Heteroatom Alkylation and Arylation
OtherReaction
99d80846228eaef6ce19530e5c1c07fddd1659a06affdcd620742fe97a34da2c
46ffa02bcab28066025af1fc8314e1e9a0b26f78b0ff559fab0e87808d67ee23
O=C1CO[C@H](c2ccc(OCc3ccccc3)cc2)c2ccccc2N1
[C:1]-[#8:2]-[C:3](=[O;D1;H0:4])-[CH;D2;+0:5]=[CH;D2;+0:6]-[C:7](=[O;D1;H0:8])-[#7:9](-[C:10])-[c:11]:[c:12](-[CH;D3;+0:13](-[OH;D1;+0:14])-[c:15](:[c:16]):[c:17]):[c:18]>>[C:1]-[#8:2]-[C:3](=[O;D1;H0:4])-[CH2;D2;+0:5]-[C@H;D3;+0:6]1-[O;H0;D2;+0:14]-[C@H;D3;+0:13](-[c:15](:[c:16]):[c:17])-[c:12](:[c:18]):[c:11]-[#7:9](...
81.7
[{"value": 81.7, "product": "C(C1=CC=CC=C1)OC1=CC(=C(C=C1)[C@H]1O[C@@H](C(N(C2=C1C=C(C=C2)Cl)CC(C)(C)C)=O)CC(=O)OCC)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
To a mixture of ethyl 3-[N-[4-chloro-2-(4-benzyloxy-α-hydroxy-2-methoxybenzyl)-phenyl]-N-neopentylcarbamoyl]acrylate (12 g), potassium carbonate (5.9 g) and ethanol (150 ml) was stirred for 24 h. After the mixture was concentrated in vacuo, the residue was diluted with water (200 ml) and extracted with ethyl acetate (2...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary alcohol
Ester.Ether
null
c1ccc2c(c1)COCC[NH]2
c1ccccc1.c1ccccc1.c1ccc2c(c1)COCC[NH]2
null
C(C)O
null
24
CCOC(=O)C=CC(=O)N(CC(C)(C)C)c1ccc(Cl)cc1C(O)c1ccc(OCc2ccccc2)cc1OC>C(C)O>CCOC(=O)C[C@H]1O[C@H](c2ccc(OCc3ccccc3)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-077138807f014cf5b7519e136115f695
CCI.CCOC(=O)C[C@H]1O[C@H](c2ccc(O)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O>>CCOC(=O)C[C@H]1O[C@H](c2ccc(OCC)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O
ClC=1C=CC2=C([C@H](O[C@@H](C(N2CC(C)(C)C)=O)CC(=O)OCC)C2=C(C=C(C=C2)O)OC)C1.C(C)I.C([O-])([O-])=O.[K+].[K+].CN(C=O)C>>ClC=1C=CC2=C([C@H](O[C@@H](C(N2CC(C)(C)C)=O)CC(=O)OCC)C2=C(C=C(C=C2)OCC)OC)C1
I[CH2:15][CH3:16].[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][C@H:7]1[O:8][C@H:9]([c:10]2[cH:11][cH:12][c:13]([OH:14])[cH:17][c:18]2[O:19][CH3:20])[c:21]2[cH:22][c:23]([Cl:24])[cH:25][cH:26][c:27]2[N:28]([CH2:29][C:30]([CH3:31])([CH3:32])[CH3:33])[C:34]1=[O:35]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][C@H:7]1[O:8][C@H:9]([...
CCI.CCOC(=O)C[C@H]1O[C@H](c2ccc(O)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O
CCOC(=O)C[C@H]1O[C@H](c2ccc(OCC)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O
null
null
O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
O=C1CO[C@H](c2ccccc2)c2ccccc2N1
I-[CH2;D2;+0:1]-[C;D1;H3:2].[OH;D1;+0:3]-[c:4](:[c:5]):[c:6]>>[C;D1;H3:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:3]-[c:4](:[c:5]):[c:6]
null
[]
null
null
3
HOUR
A mixture of ethyl trans-7-chloro-5-(4-hydroxy-2-methoxyphenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetate (0.25 g), ethyl iodide (0.06 ml), potassium carbonate (0.15 g) and N,N-dimethylformamide (200 ml) was stirred for 3 h. The mixture was diluted with water (50 ml) and extracted with ethyl acet...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccc2c(c1)COCC[NH]2
HI
O
null
3
CCI.CCOC(=O)C[C@H]1O[C@H](c2ccc(O)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O>O>CCOC(=O)C[C@H]1O[C@H](c2ccc(OCC)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-272d2516523f4474ab76d5851158b256
CCOC(=O)C[C@H]1O[C@H](c2ccc(OCC)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O>>CCOc1ccc([C@H]2O[C@H](CC(=O)O)C(=O)N(CC(C)(C)C)c3ccc(Cl)cc32)c(OC)c1
C(C)OC1=CC(=C(C=C1)[C@H]1O[C@@H](C(N(C2=C1C=C(C=C2)Cl)CC(C)(C)C)=O)CC(=O)OCC)OC.C([O-])([O-])=O.[K+].[K+].CO.O1CCCC1>>C(C)OC1=CC(=C(C=C1)[C@H]1O[C@@H](C(N(C2=C1C=C(C=C2)Cl)CC(C)(C)C)=O)CC(=O)O)OC
CC[O:14][C:12]([CH2:11][C@H:10]1[O:9][C@H:8]([c:7]2[cH:6][cH:5][c:4]([O:3][CH2:2][CH3:1])[cH:33][c:30]2[O:31][CH3:32])[c:29]2[c:23]([cH:24][cH:25][c:26]([Cl:27])[cH:28]2)[N:17]([CH2:18][C:19]([CH3:20])([CH3:21])[CH3:22])[C:15]1=[O:16])=[O:13]>>[CH3:1][CH2:2][O:3][c:4]1[cH:5][cH:6][c:7]([C@H:8]2[O:9][C@H:10]([CH2:11][C:...
CCOC(=O)C[C@H]1O[C@H](c2ccc(OCC)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O
CCOc1ccc([C@H]2O[C@H](CC(=O)O)C(=O)N(CC(C)(C)C)c3ccc(Cl)cc32)c(OC)c1
null
null
O
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C1CO[C@H](c2ccccc2)c2ccccc2N1
C-C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
null
[]
null
null
null
null
A mixture of ethyl trans-5-(4-ethoxy-2-methoxyphenyl)-7-chloro-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetate (0.18 g), potassium carbonate (0.10 g), methanol (10 ml), tetrahydrofuran (10 ml) and water (5 ml) was refluxed for 1.5 h. The resulting mixture was concentrated in vacuo, acidified with 1N hy...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccc2c(c1)COCC[NH]2
Other
O
null
null
CCOC(=O)C[C@H]1O[C@H](c2ccc(OCC)cc2OC)c2cc(Cl)ccc2N(CC(C)(C)C)C1=O>O>CCOc1ccc([C@H]2O[C@H](CC(=O)O)C(=O)N(CC(C)(C)C)c3ccc(Cl)cc32)c(OC)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-519d1ed0c254438c8f86070fac54bfc1
N#Cc1n[nH]c(NC(=O)C(F)(F)F)c1SC(F)(F)F>>N#Cc1n[nH]c(N)c1SC(F)(F)F
C(#N)C1=NNC(=C1SC(F)(F)F)NC(C(F)(F)F)=O.[OH-].[NH4+].Cl>>C(#N)C1=NNC(=C1SC(F)(F)F)N
O=C(C(F)(F)F)[NH:7][c:6]1[nH:5][n:4][c:3]([C:2]#[N:1])[c:8]1[S:9][C:10]([F:11])([F:12])[F:13]>>[N:1]#[C:2][c:3]1[n:4][nH:5][c:6]([NH2:7])[c:8]1[S:9][C:10]([F:11])([F:12])[F:13]
N#Cc1n[nH]c(NC(=O)C(F)(F)F)c1SC(F)(F)F
N#Cc1n[nH]c(N)c1SC(F)(F)F
null
null
CO.C(C)(=O)OCC
Reduction
Hydrogenolysis of amides/imides/carbamates
44b36597c7daf0608965c52c8db8a9220c21d9447ce54e0af375898475f3493f
caaeb83af2cb178156ae90fe7f610a106cd4bb5397d23f56d37a7fe11e2668ed
c1cn[nH]c1
F-C(-F)(-F)-C(=O)-[NH;D2;+0:1]-[c:2]1:[#7;a:3]:[#7;a:4]:[c:5]:[c:6]:1>>[NH2;D1;+0:1]-[c:2]1:[#7;a:3]:[#7;a:4]:[c:5]:[c:6]:1
87.6
[{"value": 87.6, "product": "C(#N)C1=NNC(=C1SC(F)(F)F)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
HOUR
The product of Step E (55 g, 181 mmoles) was dissolved in methanol. 100 ml of ammonium hydroxide were added, the solution was refluxed for 3 hours and then stirred at room temperature for 15 hours. The methanolic solution was brought to pH7 using concentrated aqueous hydrochloric acid and diluted with ethyl acetate. Th...
10.6084/m9.figshare.5104873.v1
null
Trifluoro group.Secondary amide
Primary amine
null
null
c1cn[nH]c1
Other
CO.C(C)(=O)OCC
null
15
N#Cc1n[nH]c(NC(=O)C(F)(F)F)c1SC(F)(F)F>CO.C(C)(=O)OCC>N#Cc1n[nH]c(N)c1SC(F)(F)F
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-473dec5ce90f484b83b1114372213153
CCOC(=S)CC.CCOc1ccc(N)cc1>>CCOc1ccc2c(c1)CC(=O)N2
C(C)N(CC)CC.C(C)OC1=CC=C(N)C=C1.CCC(=S)OCC.ClCl>>C(C)OC=1C=C2CC(NC2=CC1)=O
CC[O:12][C:11](=S)[CH2:10]C.[CH3:1][CH2:2][O:3][c:4]1[cH:5][cH:6][c:7]([NH2:13])[cH:8][cH:9]1>>[CH3:1][CH2:2][O:3][c:4]1[cH:5][cH:6][c:7]2[c:8]([cH:9]1)[CH2:10][C:11](=[O:12])[NH:13]2
CCOC(=S)CC.CCOc1ccc(N)cc1
CCOc1ccc2c(c1)CC(=O)N2
null
null
C(Cl)Cl.O
Acylation
OtherReaction
a2a74f97cf7b487de6b223d2dc53dd6aa5e8f47b1840b7ace2677d5fc1e0131e
7ad4bf7309306986e6cc349c7bc628011e853b7eb203cf188a8de27e64e52865
O=C1Cc2ccccc2N1
C-C-[O;H0;D2;+0:1]-[C;H0;D3;+0:2](=S)-[CH2;D2;+0:3]-C.[NH2;D1;+0:4]-[c:5](:[c:6]):[cH;D2;+0:7]:[c:8]:[c:9]>>[O;H0;D1;+0:1]=[C;H0;D3;+0:2]1-[CH2;D2;+0:3]-[c;H0;D3;+0:7](:[c:8]:[c:9]):[c:5](:[c:6])-[NH;D2;+0:4]-1
null
[]
null
null
5
MINUTE
23.6 g of ethyl methylthioacetate in 60 ml of DCM are added to a solution, cooled to about -70° C., of 12.5 g of chlorine in 400 ml of DCM. After stirring for 5 minutes at the same temperature, a solution of 4-ethoxyaniline (48.3 g) in 120 ml of DCM is added. The mixture is stirred for one hour at about -70° C., 39.3 m...
10.6084/m9.figshare.5104873.v1
null
Ether.Primary amine.Thiocarbonyl
Secondary amide
c1ccccc1
c1ccc2c(c1)CCN2
c1ccc2c(c1)CCN2
Other
C(Cl)Cl.O
null
0.083333
CCOC(=S)CC.CCOc1ccc(N)cc1>C(Cl)Cl.O>CCOc1ccc2c(c1)CC(=O)N2
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-ae97b39090304851b44154a73304af2d
O=C1Nc2ccc(Cl)cc2C1=O.c1ccccc1>>O=C1Nc2ccc(Cl)cc2C1(c1ccccc1)c1ccccc1
ClC=1C=C2C(C(NC2=CC1)=O)=O.[Cl-].[Al+3].[Cl-].[Cl-].C1=CC=CC=C1>>ClC=1C=C2C(C(NC2=CC1)=O)(C1=CC=CC=C1)C1=CC=CC=C1
O=[C:11]1[C:2](=[O:1])[NH:3][c:4]2[cH:5][cH:6][c:7]([Cl:8])[cH:9][c:10]21.[cH:12]1[cH:19][cH:20][cH:21][cH:22][cH:23]1>>[O:1]=[C:2]1[NH:3][c:4]2[cH:5][cH:6][c:7]([Cl:8])[cH:9][c:10]2[C:11]1([c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1)[c:18]1[cH:19][cH:20][cH:21][cH:22][cH:23]1
O=C1Nc2ccc(Cl)cc2C1=O.c1ccccc1
O=C1Nc2ccc(Cl)cc2C1(c1ccccc1)c1ccccc1
null
null
null
C-C Coupling
OtherReaction
dba4da327e7262cdcc29a8207cdf08b13f4d7581c1f62dc179c070e46d100989
06a42e352cf517302d592bf38a2fd11b220014e39071074dc7becb6ee0bee4b2
O=C1Nc2ccccc2C1(c1ccccc1)c1ccccc1
O=[C;H0;D3;+0:1]1-[C:2](=[O;D1;H0:3])-[#7:4]-[c:5]:[c:6]-1:[c:7].[c:8]1:[c:9]:[c:10]:[cH;D2;+0:11]:[cH;D2;+0:12]:[cH;D2;+0:13]:1>>[O;D1;H0:3]=[C:2]1-[#7:4]-[c:5]:[c:6](:[c:7])-[C;H0;D4;+0:1]-1(-[c:14]1:[cH;D2;+0:13]:[c:8]:[c:9]:[c:10]:[cH;D2;+0:11]:1)-[c;H0;D3;+0:12](:[c:15]:[c:16]):[c:17]:[c:18]
null
[]
null
null
null
null
This compound is prepared by the method described in Helv. Chim. Acta, 1946, 29, 415-431, by the reaction of benzene with 5-chloroisatin in the presence of aluminum chloride. M.p.=281° C. Conditions: See reaction.notes.procedure_details. Workup: This compound is prepared by the method
10.6084/m9.figshare.5104873.v1
null
Ketone
null
c1ccc2c(c1)CCN2.c1ccccc1
c1ccc2c(c1)CCN2.c1ccccc1.c1ccccc1
c1ccc2c(c1)CCN2.c1ccccc1.c1ccccc1
null
null
null
null
O=C1Nc2ccc(Cl)cc2C1=O.c1ccccc1>>O=C1Nc2ccc(Cl)cc2C1(c1ccccc1)c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-82e1641a8537406cb79348a3cda038e6
CCO.O=C(Cl)c1ccc(F)cc1>>CCOC(=O)c1ccc(F)cc1
FC1=CC=C(C(=O)Cl)C=C1.C(C)O>>FC1=CC=C(C(=O)OCC)C=C1
[CH3:1][CH2:2][OH:3].Cl[C:4](=[O:5])[c:6]1[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][cH:8][c:9]([F:10])[cH:11][cH:12]1
CCO.O=C(Cl)c1ccc(F)cc1
CCOC(=O)c1ccc(F)cc1
null
null
null
Acylation
Schotten-Baumann to ester
6cefe709828c5bd4655f254e75d5dff9e8876e192e7dd47256c1bc0067bc5291
d8a7643b81ed07a6f633aa99465180dfa0565e61ae25aef36338ebb9837c9cef
c1ccccc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[C:7]-[OH;D1;+0:8]>>[C;D1;H3:6]-[C:7]-[O;H0;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
null
[]
null
null
null
null
A mixture containing 35 g of 4-fluorobenzoyl chloride in 50 ml of 100% ethanol is refluxed for 15 minutes. 35 g of the ethyl 4-fluorobenzoate obtained are mixed with 22 g of imidazole and 61 g of potassium carbonate in 35 ml of DMSO. The mixture is heated for 18 hours at 120°-130° C. and 500 ml of iced water are then a...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary alcohol
Ester
null
null
c1ccccc1
HCl
null
null
null
CCO.O=C(Cl)c1ccc(F)cc1>>CCOC(=O)c1ccc(F)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-8a2792e0ff14486c99220c32eed53e32
O=C(O)CCCCC/C=C/CCCCCCCCO>>O=C1CCCCC/C=C\CCCCCCCCO1
[OH-].[K+].C(CCCCO)CCC/C=C/CCCCCC(=O)O>>C1CCCCOC(=O)CCCCC/C=C\CCC1
O=[C:2]([OH:1])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]/[CH:8]=[CH:9]/[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][OH:18]>>[O:1]=[C:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]/[CH:8]=[CH:9]\[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][O:18]1
O=C(O)CCCCC/C=C/CCCCCCCCO
O=C1CCCCC/C=C\CCCCCCCCO1
null
null
null
Miscellaneous
OtherReaction
d008debc606a42ffabf18996f7a12af8bf05125aaa7394ef1bb59bbb42455bcf
aace2e495d6e25bd670c830d3d27c657c78d937f84a32acc2423ead6678aa7cd
O=C1CCCCC/C=C\CCCCCCCCO1
O=[C;H0;D3;+0:1](-[OH;D1;+0:2])-[C:3]-[C:4].[C:5]-[C:6]-[OH;D1;+0:7]>>[C:5]-[C:6]-[O;H0;D2;+0:7]-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[C:3]-[C:4]
null
[]
180
CELSIUS
null
null
Alternatively, the ester may be saponified to obtain the ambrettolic acid. The crude ambrettolic acid obtained by saponification was transformed into its glycerine polyester by heating under a slight vacuum at 180° C. for a period of 4 to 5 hours. The resulting polyesters were then depolymerized in the presence of a mi...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
C1=C\CCCCCCOCCCCCCCC/1
C1=C\CCCCCCOCCCCCCCC/1
HO-
null
180
null
O=C(O)CCCCC/C=C/CCCCCCCCO>>O=C1CCCCC/C=C\CCCCCCCCO1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-99c88818328441daaf858d5d4bfeac19
Cc1ccc(O)cn1.OO>>O=Cc1ccc(O)cn1
Cl.OC=1C=CC(=NC1)C.OO.C([O-])([O-])=O.[Na+].[Na+].OO>>C(=O)C1=NC=C(C=C1)O
[CH3:2][c:3]1[cH:4][cH:5][c:6]([OH:7])[cH:8][n:9]1.O[OH:1]>>[O:1]=[CH:2][c:3]1[cH:4][cH:5][c:6]([OH:7])[cH:8][n:9]1
Cc1ccc(O)cn1.OO
O=Cc1ccc(O)cn1
null
null
C(C)(=O)O.N1=CC=CC=C1
Heteroatom Alkylation and Arylation
OtherReaction
7e1870c03b602e61df02a0c51095711e42253be2dbc5d565388a68551b4e83d3
9ad8303996fc77b37f471d05459c96affefccf7f394ffdf3b2e3c59a7a7dabb7
c1ccncc1
O-[OH;D1;+0:1].[CH3;D1;+0:2]-[c:3](:[c:4]):[#7;a:5]:[c:6]>>[O;H0;D1;+0:1]=[CH;D2;+0:2]-[c:3](:[c:4]):[#7;a:5]:[c:6]
32
[{"value": 32.0, "product": "C(=O)C1=NC=C(C=C1)O", "details": "PERCENTYIELD", "is_desired": false}]
120
CELSIUS
3
HOUR
To a stirred solution of 21.8 g of 5-hydroxy-2-picoline (0.2 mol) in 200 mL of glacial acetic acid was added 18 mL of 30% hydrogen peroxide (0.159 mol) in one portion. The mixture was heated in an oil bath at 80°-85° C. with stirring for 3 h. Then another 18 mL of hydrogen peroxide was added and the mixture was stirred...
10.6084/m9.figshare.5104873.v1
null
Peroxide
Aldehyde
null
null
c1ccncc1
HO-
C(C)(=O)O.N1=CC=CC=C1
120
3
Cc1ccc(O)cn1.OO>C(C)(=O)O.N1=CC=CC=C1>O=Cc1ccc(O)cn1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-dc420121d02f4dbbbc0f71fe5ec58124
NNC(=O)Nc1ccccc1.O=Cc1ncccc1O>>O=C(NN=Cc1ncccc1O)Nc1ccccc1
C1(=CC=CC=C1)NC(NN)=O.OC=1C(=NC=CC1)C=O>>OC=1C(=NC=CC1)C=NNC(=O)NC1=CC=CC=C1
[O:1]=[C:2]([NH:3][NH2:4])[NH:13][c:14]1[cH:15][cH:16][cH:17][cH:18][cH:19]1.O=[CH:5][c:6]1[n:7][cH:8][cH:9][cH:10][c:11]1[OH:12]>>[O:1]=[C:2]([NH:3][N:4]=[CH:5][c:6]1[n:7][cH:8][cH:9][cH:10][c:11]1[OH:12])[NH:13][c:14]1[cH:15][cH:16][cH:17][cH:18][cH:19]1
NNC(=O)Nc1ccccc1.O=Cc1ncccc1O
O=C(NN=Cc1ncccc1O)Nc1ccccc1
null
null
O.C(C)O
Heteroatom Alkylation and Arylation
OtherReaction
d96921e54ea5a9886efe70451a5b6747abf630b51f5287f460084f46e96e1d54
24296832c6ee4d0b5568b975c5df51fd66c85a5bdc41f3275d634cea600f4109
O=C(NN=Cc1ccccn1)Nc1ccccc1
O=[CH;D2;+0:1]-[c:2](:[c:3]):[#7;a:4]:[c:5].[#7:6]-[C:7](=[O;D1;H0:8])-[#7:9]-[NH2;D1;+0:10]>>[#7:6]-[C:7](=[O;D1;H0:8])-[#7:9]-[N;H0;D2;+0:10]=[CH;D2;+0:1]-[c:2](:[c:3]):[#7;a:4]:[c:5]
99
[{"value": 99.0, "product": "OC=1C(=NC=CC1)C=NNC(=O)NC1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 97.2, "product": "OC=1C(=NC=CC1)C=NNC(=O)NC1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
4-Phenyl semicarbazide (4.91 g, 33 mmol) was added to a suspension of 3-hydroxy-2-pyridine carbaldehyde (4.0 g, 33 mmol) in a mixture of ethanol water (30 mL:40 mL). The reaction mixture was stirred at room temperature for 3 h and the yellow product was collected by filtration. The yellow precipitate was washed with Et...
10.6084/m9.figshare.5104873.v1
null
Acylhydrazine.Aldehyde
Hydrazone amide
null
null
c1ccncc1.c1ccccc1
HO-
O.C(C)O
null
3
NNC(=O)Nc1ccccc1.O=Cc1ncccc1O>O.C(C)O>O=C(NN=Cc1ncccc1O)Nc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-0871baecec9c4c268d5490bd44c95dc8
CN(C)C(=O)c1cc(O)c(C=NNC(N)=O)[n+](C)c1>>CN(C)C(=O)c1c(O)cc[n+](C)c1C=NNC(N)=O
[Cl-].NC(=O)NN=CC1=[N+](C=C(C=C1O)C(N(C)C)=O)C.C(=O)C1=NC=C(C=C1)O.[Cl-].NC(=O)NN=CC1=[N+](C(=CC(=C1C(N(C)C)=O)O)C)C.OC=1C(=NC=CC1)C=O.OC=1C(=NC=CC1)C=O.OC=1C(=NC(=CC1)C)C=O>>[Cl-].NC(=O)NN=CC1=[N+](C=CC(=C1C(N(C)C)=O)O)C
[CH3:1][N:2]([CH3:3])[C:4](=[O:5])[c:6]1[cH:9][c:7]([OH:8])[c:13]([CH:14]=[N:15][NH:16][C:17]([NH2:18])=[O:19])[n+:11]([CH3:12])[cH:10]1>>[CH3:1][N:2]([CH3:3])[C:4](=[O:5])[c:6]1[c:7]([OH:8])[cH:9][cH:10][n+:11]([CH3:12])[c:13]1[CH:14]=[N:15][NH:16][C:17]([NH2:18])=[O:19]
CN(C)C(=O)c1cc(O)c(C=NNC(N)=O)[n+](C)c1
CN(C)C(=O)c1c(O)cc[n+](C)c1C=NNC(N)=O
null
null
null
Miscellaneous
OtherReaction
d9b18d697b4d4db9243a5c6f5ddeb225e493174381e1c97208f65b6bb99201d8
1208f5f10c31f751480b67448a35dc747ab74c6e532be327ba8985b70d351e81
c1cc[nH+]cc1
[C;D1;H3:1]-[#7;a;+:2]1:[cH;D2;+0:3]:[c;H0;D3;+0:4](-[C:5](=[O;D1;H0:6])-[#7:7](-[C;D1;H3:8])-[C;D1;H3:9]):[cH;D2;+0:10]:[c;H0;D3;+0:11](-[O;D1;H1:12]):[c;H0;D3;+0:13]:1-[C:14]=[#7:15]-[#7:16]-[C:17]=[O;D1;H0:18]>>[C;D1;H3:1]-[#7;a;+:2]1:[cH;D2;+0:3]:[cH;D2;+0:10]:[c;H0;D3;+0:11](-[O;D1;H1:12]):[c;H0;D3;+0:4](-[C:5](=[...
null
[]
null
null
null
null
2-[[(Aminocarbonyl)hydrazono]methyl]-3-(N,N-dimethylcarbamoyl)hydroxy-1,6-dimethyl pyridinium chloride can be made by the same procedure replacing 3-hydroxy-2-pyridine aldehyde in the above example with 3-hydroxy-6-methyl-2-pyridine aldehyde. 2-[[(Aminocarbonyl)hydrazono] methyl] -5-(N ,N-dimethylcarbamoyl)hydroxy-1-me...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Aromatic alcohol
C1=CC=[NH+]C=C1
C1=CC=[NH+]C=C1
C1=CC=[NH+]C=C1
null
null
null
null
CN(C)C(=O)c1cc(O)c(C=NNC(N)=O)[n+](C)c1>>CN(C)C(=O)c1c(O)cc[n+](C)c1C=NNC(N)=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-0570825de3de42f284cb61b4bb3699df
Cc1ccc(O)c(CO)n1>>Cc1ccc(O)c(C=O)n1
OC=1C(=NC(=CC1)C)CO.[Se](=O)=O>>OC=1C(=NC(=CC1)C)C=O
[CH3:1][c:2]1[cH:3][cH:4][c:5]([OH:6])[c:7]([CH2:8][OH:9])[n:10]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([OH:6])[c:7]([CH:8]=[O:9])[n:10]1
Cc1ccc(O)c(CO)n1
Cc1ccc(O)c(C=O)n1
null
null
C(C)O.O1CCOCC1
Oxidation
Oxidation or Dehydrogenation of Alcohols to Aldehydes and Ketones
41bfa9deea81b465c88ad21fdfb64a2e1ba29490558cf430df132cb98b4a538b
0a03c6724c1862e8f86d4a463afda55b8e067dc6cb42597b472eb7cabc03eda3
c1ccncc1
[OH;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[#7;a:5]:[c:6]>>[O;H0;D1;+0:1]=[CH;D2;+0:2]-[c:3](:[c:4]):[#7;a:5]:[c:6]
57.3
[{"value": 56.0, "product": "OC=1C(=NC(=CC1)C)C=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 57.3, "product": "OC=1C(=NC(=CC1)C)C=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
3-Hydroxy-6-methyl-2-pyridine methanol (20.0 g, 0.14 mol) and selenium dioxide(8.0 g, 72 mmol) were dissolved in 140 mL of 1,4-dioxane and 280 mL of absolute ethanol. The resulting mixture was heated at 80°-85° C. for 12 h. The selenium precipitate was removed by filtration and the filtrate was concentrated to dryness ...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
Aldehyde
null
null
c1ccncc1
null
C(C)O.O1CCOCC1
null
null
Cc1ccc(O)c(CO)n1>C(C)O.O1CCOCC1>Cc1ccc(O)c(C=O)n1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-45cdb5a182c44dd2b68a1aad0b23d6f4
CC(O)(C(=O)O)C(F)(F)F.Nc1cccc2c1C(=O)c1ccccc1CO2>>CC(O)(C(=O)Nc1cccc2c1C(=O)c1ccccc1CO2)C(F)(F)F
FC(C(C(=O)O)(C)O)(F)F.S(=O)(Cl)Cl.NC1=CC=CC=2OCC3=C(C(C21)=O)C=CC=C3>>FC(C(C(=O)NC1=CC=CC=2OCC3=C(C(C21)=O)C=CC=C3)(C)O)(F)F
O[C:4]([C:2]([CH3:1])([OH:3])[C:23]([F:24])([F:25])[F:26])=[O:5].[NH2:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[C:13](=[O:14])[c:15]1[cH:16][cH:17][cH:18][cH:19][c:20]1[CH2:21][O:22]2>>[CH3:1][C:2]([OH:3])([C:4](=[O:5])[NH:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[C:13](=[O:14])[c:15]1[cH:16][cH:17][cH:18][cH:19][c:20]...
CC(O)(C(=O)O)C(F)(F)F.Nc1cccc2c1C(=O)c1ccccc1CO2
CC(O)(C(=O)Nc1cccc2c1C(=O)c1ccccc1CO2)C(F)(F)F
null
null
CC(=O)N(C)C.C(C)(=O)OCC
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C1c2ccccc2COc2ccccc21
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C;D1;H3:4])(-[O;D1;H1:5])-[C:6](-[F;D1;H0:7])(-[F;D1;H0:8])-[F;D1;H0:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]-[C:14]=[O;D1;H0:15]>>[C;D1;H3:4]-[C:3](-[O;D1;H1:5])(-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]-[C:14]=[O;D1;H0:15])-[C:6](-[F;D1;H0:7])(-[F;D1;H0:...
30
[{"value": 30.0, "product": "FC(C(C(=O)NC1=CC=CC=2OCC3=C(C(C21)=O)C=CC=C3)(C)O)(F)F", "details": "PERCENTYIELD", "is_desired": false}]
-10
CELSIUS
1
HOUR
In dimethylacetamide (3 ml) was dissolved 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid (0.17 g, 1.1 mmol), and thionyl chloride (80 μl, 1.1 mmol) was added thereto at -15° C., followed by stirring at -15 to -5° C. for one hour. To this reaction mixture was added 1-amino-6,11-dihydrodibenz[b,e]oxepin-11-one obtained...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccc2c(c1)COc1ccccc1C2
HO-
CC(=O)N(C)C.C(C)(=O)OCC
-10
1
CC(O)(C(=O)O)C(F)(F)F.Nc1cccc2c1C(=O)c1ccccc1CO2>CC(=O)N(C)C.C(C)(=O)OCC>CC(O)(C(=O)Nc1cccc2c1C(=O)c1ccccc1CO2)C(F)(F)F
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-c07975784c3e442c8e7370feccd7700d
CC(O)(C(=O)O)C(F)(F)F.Nc1cccc2c1C(=O)c1sccc1CO2>>CC(O)(C(=O)Nc1cccc2c1C(=O)c1sccc1CO2)C(F)(F)F
FC(C(C(=O)O)(C)O)(F)F.S(=O)(Cl)Cl.NC1=CC=CC2=C1C(C1=C(CO2)C=CS1)=O>>FC(C(C(=O)NC1=CC=CC2=C1C(C1=C(CO2)C=CS1)=O)(C)O)(F)F
O[C:4]([C:2]([CH3:1])([OH:3])[C:22]([F:23])([F:24])[F:25])=[O:5].[NH2:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[C:13](=[O:14])[c:15]1[s:16][cH:17][cH:18][c:19]1[CH2:20][O:21]2>>[CH3:1][C:2]([OH:3])([C:4](=[O:5])[NH:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[C:13](=[O:14])[c:15]1[s:16][cH:17][cH:18][c:19]1[CH2:20][O:21]2...
CC(O)(C(=O)O)C(F)(F)F.Nc1cccc2c1C(=O)c1sccc1CO2
CC(O)(C(=O)Nc1cccc2c1C(=O)c1sccc1CO2)C(F)(F)F
null
null
CC(=O)N(C)C.C(C)(=O)OCC
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C1c2ccccc2OCc2ccsc21
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C;D1;H3:4])(-[O;D1;H1:5])-[C:6](-[F;D1;H0:7])(-[F;D1;H0:8])-[F;D1;H0:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]-[C:14]=[O;D1;H0:15]>>[C;D1;H3:4]-[C:3](-[O;D1;H1:5])(-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]-[C:14]=[O;D1;H0:15])-[C:6](-[F;D1;H0:7])(-[F;D1;H0:...
89
[{"value": 89.0, "product": "FC(C(C(=O)NC1=CC=CC2=C1C(C1=C(CO2)C=CS1)=O)(C)O)(F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
In dimethylacetamide (3 ml) was dissolved 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid (0.32 g, 2.03 mmol), and thionyl chloride (148 μl, 2.03 mmol) was added thereto at -15° C., followed by stirring at -15° to -5° C. for one hour. To this reaction mixture was added 9-amino-4,10-dihydrothieno[3,2-c][1]benzoxepin-10...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccc2c(c1)Cc1sccc1CO2
HO-
CC(=O)N(C)C.C(C)(=O)OCC
null
1
CC(O)(C(=O)O)C(F)(F)F.Nc1cccc2c1C(=O)c1sccc1CO2>CC(=O)N(C)C.C(C)(=O)OCC>CC(O)(C(=O)Nc1cccc2c1C(=O)c1sccc1CO2)C(F)(F)F
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-6484a284b0aa46eaae0c0af132625719
C[C@](O)(C(=O)O)C(F)(F)F.Nc1cccc2c1C(=O)c1sccc1CO2>>C[C@](O)(C(=O)Nc1cccc2c1C(=O)c1sccc1CO2)C(F)(F)F
NC1=CC=CC2=C1C(C1=C(CO2)C=CS1)=O.FC([C@@](C(=O)O)(C)O)(F)F>>FC([C@@](C(=O)NC1=CC=CC2=C1C(C1=C(CO2)C=CS1)=O)(C)O)(F)F
O[C:4]([C@:2]([CH3:1])([OH:3])[C:22]([F:23])([F:24])[F:25])=[O:5].[NH2:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[C:13](=[O:14])[c:15]1[s:16][cH:17][cH:18][c:19]1[CH2:20][O:21]2>>[CH3:1][C@:2]([OH:3])([C:4](=[O:5])[NH:6][c:7]1[cH:8][cH:9][cH:10][c:11]2[c:12]1[C:13](=[O:14])[c:15]1[s:16][cH:17][cH:18][c:19]1[CH2:20][O:21...
C[C@](O)(C(=O)O)C(F)(F)F.Nc1cccc2c1C(=O)c1sccc1CO2
C[C@](O)(C(=O)Nc1cccc2c1C(=O)c1sccc1CO2)C(F)(F)F
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C1c2ccccc2OCc2ccsc21
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C;D1;H3:4])(-[O;D1;H1:5])-[C:6](-[F;D1;H0:7])(-[F;D1;H0:8])-[F;D1;H0:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]-[C:14]=[O;D1;H0:15]>>[C;D1;H3:4]-[C:3](-[O;D1;H1:5])(-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]-[C:14]=[O;D1;H0:15])-[C:6](-[F;D1;H0:7])(-[F;D1;H0:...
35
[{"value": 35.0, "product": "FC([C@@](C(=O)NC1=CC=CC2=C1C(C1=C(CO2)C=CS1)=O)(C)O)(F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Substantially the same procedure as in Example 1 was repeated using 9-amino-4,10-dihydrothieno[3,2-c][1]benzoxepin-10-one obtained in Reference Example 11 (0.840 g, 3.63 mmol) and (S)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid obtained in Reference Example 27 (1.14 g, 7.26 mmol) to give Compound 33 (0.47 g, 35%)....
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccc2c(c1)Cc1sccc1CO2
HO-
null
null
null
C[C@](O)(C(=O)O)C(F)(F)F.Nc1cccc2c1C(=O)c1sccc1CO2>>C[C@](O)(C(=O)Nc1cccc2c1C(=O)c1sccc1CO2)C(F)(F)F
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-08ed9fc621264a2f9632e16668245bd7
CC(=O)Nc1cccc(O)c1.COC(=O)c1ccccc1CBr>>COC(=O)c1ccccc1COc1cccc(NC(C)=O)c1
C([O-])(O)=O.[Na+].BrCC1=C(C(=O)OC)C=CC=C1.C(C)(=O)NC=1C=C(C=CC1)O.C([O-])([O-])=O.[Cs+].[Cs+]>>C(C)(=O)NC=1C=C(OCC2=C(C(=O)OC)C=CC=C2)C=CC1
[OH:12][c:13]1[cH:14][cH:15][cH:16][c:17]([NH:18][C:19]([CH3:20])=[O:21])[cH:22]1.Br[CH2:11][c:10]1[c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:6][cH:7][cH:8][cH:9]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][cH:8][cH:9][c:10]1[CH2:11][O:12][c:13]1[cH:14][cH:15][cH:16][c:17]([NH:18][C:19]([CH3:20])=[O:21])[cH:22]1
CC(=O)Nc1cccc(O)c1.COC(=O)c1ccccc1CBr
COC(=O)c1ccccc1COc1cccc(NC(C)=O)c1
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccc(COc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]-[C:5](-[#8:6])=[O;D1;H0:7].[OH;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[#8:6]-[C:5](=[O;D1;H0:7])-[c:4]:[c:2](-[CH2;D2;+0:1]-[O;H0;D2;+0:8]-[c:9](:[c:10]):[c:11]):[c:3]
61.2
[{"value": 61.0, "product": "C(C)(=O)NC=1C=C(OCC2=C(C(=O)OC)C=CC=C2)C=CC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 61.2, "product": "C(C)(=O)NC=1C=C(OCC2=C(C(=O)OC)C=CC=C2)C=CC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
To a solution of 3-acetamidophenol (1.0 g, 6.6 mmol) in dimethylformamide (10 ml) was added cesium carbonate (1.3 g, 3.9 mmol), followed by stirring at room temperature for 30 minutes. To the resulting mixture was added methyl 2-bromomethylbenzoate (1.8 g, 7.9 mmol), and the mixture was stirred overnight at room temper...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1
HBr
CN(C=O)C
null
0.5
CC(=O)Nc1cccc(O)c1.COC(=O)c1ccccc1CBr>CN(C=O)C>COC(=O)c1ccccc1COc1cccc(NC(C)=O)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-cca8c52f7ba34625b95aa6d245498aa5
CC(=O)Nc1cccc2c1C(=O)c1ccccc1CO2>>Nc1cccc2c1C(=O)c1ccccc1CO2
C(C)(=O)NC1=CC=CC=2OCC3=C(C(C21)=O)C=CC=C3.C([O-])(O)=O.[Na+]>>NC1=CC=CC=2OCC3=C(C(C21)=O)C=CC=C3
CC(=O)[NH:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]1[C:8](=[O:9])[c:10]1[cH:11][cH:12][cH:13][cH:14][c:15]1[CH2:16][O:17]2>>[NH2:1][c:2]1[cH:3][cH:4][cH:5][c:6]2[c:7]1[C:8](=[O:9])[c:10]1[cH:11][cH:12][cH:13][cH:14][c:15]1[CH2:16][O:17]2
CC(=O)Nc1cccc2c1C(=O)c1ccccc1CO2
Nc1cccc2c1C(=O)c1ccccc1CO2
null
null
Cl
Reduction
Hydrogenolysis of amides/imides/carbamates
755df58c254dea764fdda078ffd678ec540bba057c83683be04c253f1270ac7b
025f7cefe51e71668ad5d09fca32df168e9b538347403e4d5c1748073e538adc
O=C1c2ccccc2COc2ccccc21
C-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]-[C:5]=[O;D1;H0:6]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]-[C:5]=[O;D1;H0:6]
81
[{"value": 81.0, "product": "NC1=CC=CC=2OCC3=C(C(C21)=O)C=CC=C3", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
In concentrated hydrochloric acid (10 ml), 1-acetamido-6,11-dihydrodibenz[b,e]oxepin-11-one obtained in Reference Example 3(0.25 g, 0.94 mmol) was heated under reflux for 2 hours. The reaction mixture was poured into a saturated aqueous solution of sodium bicarbonate, followed by extraction with ethyl acetate (25 ml). ...
10.6084/m9.figshare.5104873.v1
null
Secondary amide
Primary amine
null
null
c1ccc2c(c1)COc1ccccc1C2
HO-
Cl
null
null
CC(=O)Nc1cccc2c1C(=O)c1ccccc1CO2>Cl>Nc1cccc2c1C(=O)c1ccccc1CO2
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-e2a46196bcf14ceb891b2c6cabfdc4c1
CC(C)(C)O.O=C(O)c1ccc2c(c1)C(=O)c1ccccc1CO2.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>>CC(C)(C)OC(=O)Nc1ccc2c(c1)C(=O)c1ccccc1CO2
C1(=CC=CC=C1)P(=O)(C1=CC=CC=C1)N=[N+]=[N-].C(=O)(O)C1=CC2=C(OCC3=C(C2=O)C=CC=C3)C=C1.C(C)N(CC)CC.C(C)(C)(C)O.C([O-])(O)=O.[Na+]>>C(C)(C)(C)OC(=O)NC1=CC2=C(OCC3=C(C2=O)C=CC=C3)C=C1
[CH3:1][C:2]([CH3:3])([CH3:4])[OH:5].O[C:6](=[O:7])[c:9]1[cH:10][cH:11][c:12]2[c:13]([cH:14]1)[C:15](=[O:16])[c:17]1[cH:18][cH:19][cH:20][cH:21][c:22]1[CH2:23][O:24]2.[N-]=[N+]=[N:8]P(=O)(c1ccccc1)c1ccccc1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][c:9]1[cH:10][cH:11][c:12]2[c:13]([cH:14]1)[C:15](=[O:16])[...
CC(C)(C)O.O=C(O)c1ccc2c(c1)C(=O)c1ccccc1CO2.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
CC(C)(C)OC(=O)Nc1ccc2c(c1)C(=O)c1ccccc1CO2
null
null
null
Protection
OtherReaction
efa4d9f6166f8f9c040ea327d55dafea4e6b153c801300b92bbe2be4bea80c34
b944663b5278c281edc6c72611c69e4309c3f5728dcd63d51413085e18c1d2e7
O=C1c2ccccc2COc2ccccc21
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c;H0;D3;+0:3](:[c:4]:[c:5]):[c:6]:[c:7]-[C:8]=[O;D1;H0:9].O=P(-[N;H0;D2;+0:10]=[N+]=[N-])(-c1:c:c:c:c:c:1)-c1:c:c:c:c:c:1.[C;D1;H3:11]-[C:12](-[C;D1;H3:13])(-[C;D1;H3:14])-[OH;D1;+0:15]>>[C;D1;H3:11]-[C:12](-[C;D1;H3:13])(-[C;D1;H3:14])-[O;H0;D2;+0:15]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2...
41
[{"value": 41.0, "product": "C(C)(C)(C)OC(=O)NC1=CC2=C(OCC3=C(C2=O)C=CC=C3)C=C1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
To tert-butanol (8.3 ml) were added diphenylphosphoryl azide (1.1 ml, 5.11 mmol), 2-carboxy-6,11-dihydrodibenz-[b,e]oxepin-11-one (Japanese Published Unexamined Patent Application No. 91040/90) (1.0 g, 3.9 mmol), and triethylamine (0.71 ml, 5.11 mmol) under an atmosphere of argon gas, followed by heating under reflux f...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Azide.Tertiary alcohol
Carbamic ester.Ether.Boc
c1ccc2c(c1)COc1ccccc1C2.c1ccccc1.c1ccccc1
c1ccc2c(c1)COc1ccccc1C2
c1ccc2c(c1)COc1ccccc1C2
HO-
null
null
null
CC(C)(C)O.O=C(O)c1ccc2c(c1)C(=O)c1ccccc1CO2.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>>CC(C)(C)OC(=O)Nc1ccc2c(c1)C(=O)c1ccccc1CO2
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-29f57c2dee5f49d5a4d2fd451c9a7d4b
CC(=O)Nc1cccc(O)c1.COC(=O)c1sccc1CBr>>COC(=O)c1sccc1COc1cccc(NC(C)=O)c1
C(C)(=O)NC=1C=C(C=CC1)O.C([O-])([O-])=O.[Cs+].[Cs+].C([O-])(O)=O.[Na+].BrCC1=C(SC=C1)C(=O)OC>>C(C)(=O)NC=1C=C(OCC2=C(SC=C2)C(=O)OC)C=CC1
[OH:11][c:12]1[cH:13][cH:14][cH:15][c:16]([NH:17][C:18]([CH3:19])=[O:20])[cH:21]1.Br[CH2:10][c:9]1[c:5]([C:3]([O:2][CH3:1])=[O:4])[s:6][cH:7][cH:8]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[s:6][cH:7][cH:8][c:9]1[CH2:10][O:11][c:12]1[cH:13][cH:14][cH:15][c:16]([NH:17][C:18]([CH3:19])=[O:20])[cH:21]1
CC(=O)Nc1cccc(O)c1.COC(=O)c1sccc1CBr
COC(=O)c1sccc1COc1cccc(NC(C)=O)c1
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccc(OCc2ccsc2)cc1
Br-[CH2;D2;+0:1]-[c:2]1:[c:3]:[c:4]:[#16;a:5]:[c:6]:1-[C:7](-[#8:8])=[O;D1;H0:9].[OH;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[#8:8]-[C:7](=[O;D1;H0:9])-[c:6]1:[#16;a:5]:[c:4]:[c:3]:[c:2]:1-[CH2;D2;+0:1]-[O;H0;D2;+0:10]-[c:11](:[c:12]):[c:13]
75.1
[{"value": 75.0, "product": "C(C)(=O)NC=1C=C(OCC2=C(SC=C2)C(=O)OC)C=CC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 75.1, "product": "C(C)(=O)NC=1C=C(OCC2=C(SC=C2)C(=O)OC)C=CC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
To a solution of 3-acetamidophenol (4.79 g, 31.7 mmol) in dimethylformamide (50 ml) was added cesium carbonate (5.67 g, 17.4 mmol), followed by stirring at room temperature for 30 minutes. To the resulting mixture was added methyl 3-bromomethyl-2-thiophenecarboxylate (8.94 g, 38.0 mmol), and the mixture was stirred ove...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccsc1.c1ccccc1
HBr
CN(C=O)C
null
0.5
CC(=O)Nc1cccc(O)c1.COC(=O)c1sccc1CBr>CN(C=O)C>COC(=O)c1sccc1COc1cccc(NC(C)=O)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-fe0aa9a207b24d63bb0ea46174e05e6e
CC(=O)Nc1ccc2c(c1)OCc1ccsc1C2=O>>Nc1ccc2c(c1)OCc1ccsc1C2=O
C(C)(=O)NC1=CC2=C(C(C3=C(CO2)C=CS3)=O)C=C1.C([O-])(O)=O.[Na+]>>NC1=CC2=C(C(C3=C(CO2)C=CS3)=O)C=C1
CC(=O)[NH:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([cH:7]1)[O:8][CH2:9][c:10]1[cH:11][cH:12][s:13][c:14]1[C:15]2=[O:16]>>[NH2:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([cH:7]1)[O:8][CH2:9][c:10]1[cH:11][cH:12][s:13][c:14]1[C:15]2=[O:16]
CC(=O)Nc1ccc2c(c1)OCc1ccsc1C2=O
Nc1ccc2c(c1)OCc1ccsc1C2=O
null
null
Cl
Reduction
Hydrogenolysis of amides/imides/carbamates
755df58c254dea764fdda078ffd678ec540bba057c83683be04c253f1270ac7b
025f7cefe51e71668ad5d09fca32df168e9b538347403e4d5c1748073e538adc
O=C1c2ccccc2OCc2ccsc21
C-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
78
[{"value": 78.0, "product": "NC1=CC2=C(C(C3=C(CO2)C=CS3)=O)C=C1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
In concentrated hydrochloric acid (15 ml), 7-acetamido-4,10-dihydrothieno[3,2-c][1]benzoxepin-10-one obtained in Reference Example 9(0.41 g, 1.51 mmol) was heated under reflux for 2 hours. The reaction mixture was poured into a saturated aqueous solution of sodium bicarbonate, followed by extraction with ethyl acetate ...
10.6084/m9.figshare.5104873.v1
null
Secondary amide
Primary amine
null
null
c1ccc2c(c1)Cc1sccc1CO2
HO-
Cl
null
null
CC(=O)Nc1ccc2c(c1)OCc1ccsc1C2=O>Cl>Nc1ccc2c(c1)OCc1ccsc1C2=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-f5ea82e1d125454e8bce94b7fc33917f
COC(=O)c1sccc1CBr.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>COC(=O)c1sccc1C[P+](c1ccccc1)(c1ccccc1)c1ccccc1.[Br-]
BrCC1=C(SC=C1)C(=O)OC.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>[Br-].COC(=O)C=1SC=CC1C[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1
[CH3:1][O:2][C:3](=[O:4])[c:5]1[s:6][cH:7][cH:8][c:9]1[CH2:10][Br:30].[P:11]([c:12]1[cH:13][cH:14][cH:15][cH:16][cH:17]1)([c:18]1[cH:19][cH:20][cH:21][cH:22][cH:23]1)[c:24]1[cH:25][cH:26][cH:27][cH:28][cH:29]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[s:6][cH:7][cH:8][c:9]1[CH2:10][P+:11]([c:12]1[cH:13][cH:14][cH:15][cH:16][cH:...
COC(=O)c1sccc1CBr.c1ccc(P(c2ccccc2)c2ccccc2)cc1
COC(=O)c1sccc1C[P+](c1ccccc1)(c1ccccc1)c1ccccc1.[Br-]
null
null
C1(=CC=CC=C1)C
Functional Group Interconversion
OtherReaction
72a5231b07f184f0ef4a0648badd4176f521b95f1ba3340a0f90d8894af47260
47a659f5704a5b7ca1b92ff731f18f109c6bde1d45152a3a393eefbd10265508
c1ccc([P+](Cc2ccsc2)(c2ccccc2)c2ccccc2)cc1
[#8:1]-[C:2](=[O;D1;H0:3])-[c:4]1:[#16;a:5]:[c:6]:[c:7]:[c:8]:1-[CH2;D2;+0:9]-[Br;H0;D1;+0:10].[c:11]:[c:12](-[P;H0;D3;+0:13](-[c:14](:[c:15]):[c:16])-[c:17](:[c:18]):[c:19]):[c:20]>>[#8:1]-[C:2](=[O;D1;H0:3])-[c:4]1:[#16;a:5]:[c:6]:[c:7]:[c:8]:1-[CH2;D2;+0:9]-[P+;H0;D4:13](-[c:12](:[c:11]):[c:20])(-[c:14](:[c:15]):[c:...
70.4
[{"value": 70.4, "product": "[Br-].COC(=O)C=1SC=CC1C[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.4, "product": "[Br-].COC(=O)C=1SC=CC1C[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
DAY
To a solution of methyl 3-bromomethyl-2-thiophenecarboxylate (7.31 g, 31.1 mmol) in toluene (90 ml) was added triphenylphosphine (7.92 g, 30.2 mmol) under ice cooling. The temperature of the mixture was raised to room temperature, followed by stirring for 2 days. The precipitated crystals were collected by filtration a...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
null
null
c1ccsc1.c1ccccc1.c1ccccc1.c1ccccc1
null
C1(=CC=CC=C1)C
null
48
COC(=O)c1sccc1CBr.c1ccc(P(c2ccccc2)c2ccccc2)cc1>C1(=CC=CC=C1)C>COC(=O)c1sccc1C[P+](c1ccccc1)(c1ccccc1)c1ccccc1.[Br-]
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-26cdb6c868e440d6955dd972d622308f
CC(C)(C)C(=O)Nc1ccc2c(c1)CCc1ccsc1C2=O>>Nc1ccc2c(c1)CCc1ccsc1C2=O
CC(C(=O)NC=1C=CC2=C(CCC3=C(SC=C3)C2=O)C1)(C)C.Cl>>NC=1C=CC2=C(CCC3=C(SC=C3)C2=O)C1
CC(C)(C)C(=O)[NH:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([cH:7]1)[CH2:8][CH2:9][c:10]1[cH:11][cH:12][s:13][c:14]1[C:15]2=[O:16]>>[NH2:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([cH:7]1)[CH2:8][CH2:9][c:10]1[cH:11][cH:12][s:13][c:14]1[C:15]2=[O:16]
CC(C)(C)C(=O)Nc1ccc2c(c1)CCc1ccsc1C2=O
Nc1ccc2c(c1)CCc1ccsc1C2=O
null
null
C(C)O
Reduction
Hydrogenolysis of amides/imides/carbamates
755df58c254dea764fdda078ffd678ec540bba057c83683be04c253f1270ac7b
025f7cefe51e71668ad5d09fca32df168e9b538347403e4d5c1748073e538adc
O=C1c2ccccc2CCc2ccsc21
C-C(-C)(-C)-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
98.8
[{"value": 98.8, "product": "NC=1C=CC2=C(CCC3=C(SC=C3)C2=O)C1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
In ethanol (10 ml) was suspended 7-trimethylacetamido-4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]thiophen-10-one obtained in Reference Example 17 (0.40 g, 1.28 mmol), and 6N hydrochloric acid (5 ml) was added thereto, followed by heating under reflux for 6 hours. After the reaction was completed, ethanol was distilled ...
10.6084/m9.figshare.5104873.v1
null
Secondary amide
Primary amine
null
null
c1ccc2c(c1)CCc1ccsc1C2
HO-
C(C)O
null
null
CC(C)(C)C(=O)Nc1ccc2c(c1)CCc1ccsc1C2=O>C(C)O>Nc1ccc2c(c1)CCc1ccsc1C2=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-61670ca8f3ee46f6b6f8d3342a1692cf
CC(=O)OC(C)=O.COC(=O)c1sccc1/C=C\c1cccc([N+](=O)[O-])c1>>COC(=O)c1sccc1/C=C\c1cccc(NC(C)=O)c1
[N+](=O)([O-])C=1C=C(\C=C/C2=C(SC=C2)C(=O)OC)C=CC1.C(C)(=O)OC(C)=O>>C(C)(=O)NC=1C=C(\C=C/C2=C(SC=C2)C(=O)OC)C=CC1
CC(=O)O[C:18]([CH3:19])=[O:20].O=[N+:17]([O-])[c:16]1[cH:15][cH:14][cH:13][c:12](/[CH:11]=[CH:10]\[c:9]2[c:5]([C:3]([O:2][CH3:1])=[O:4])[s:6][cH:7][cH:8]2)[cH:21]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[s:6][cH:7][cH:8][c:9]1/[CH:10]=[CH:11]\[c:12]1[cH:13][cH:14][cH:15][c:16]([NH:17][C:18]([CH3:19])=[O:20])[cH:21]1
CC(=O)OC(C)=O.COC(=O)c1sccc1/C=C\c1cccc([N+](=O)[O-])c1
COC(=O)c1sccc1/C=C\c1cccc(NC(C)=O)c1
null
null
null
Acylation
OtherReaction
e42a085282c3a07a051d4fb8d2fca17494e60eb1125ef7dc723a241b4f07d443
f3ba867686f6df7397dc4715602a55649ceb24345966ae3ca69ac9bcc38b3956
C(=C\c1ccsc1)\c1ccccc1
C-C(=O)-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].O=[N+;H0;D3:4](-[O-])-[c:5](:[c:6]):[c:7]>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[O;D1;H0:3])-[NH;D2;+0:4]-[c:5](:[c:6]):[c:7]
91.3
[{"value": 91.3, "product": "C(C)(=O)NC=1C=C(\\C=C/C2=C(SC=C2)C(=O)OC)C=CC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Substantially the same procedure as in Reference Example 14 was repeated using methyl (Z)-3-(3-nitrostyryl)-2-thiophenecarboxylate obtained in Reference Example 13 (3.51 g, 12.1 mmol), and also using acetic anhydride (3.43 ml, 36.3 mmol) instead of trimethylacetyl chloride, to give methyl (Z)-3-(3-acetamidostyryl)-2-th...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Nitro group
Secondary amide
null
null
c1ccsc1.c1ccccc1
HO-
null
null
null
CC(=O)OC(C)=O.COC(=O)c1sccc1/C=C\c1cccc([N+](=O)[O-])c1>>COC(=O)c1sccc1/C=C\c1cccc(NC(C)=O)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-614e99a357bf4013896cb29a932850fc
C=C[Si](Cl)(Cl)Cl.CCCCc1ccccc1>>CCCCc1c(CC[Si](Cl)(Cl)Cl)c(CC[Si](Cl)(Cl)Cl)c(CC[Si](Cl)(Cl)Cl)c(CC[Si](Cl)(Cl)Cl)c1CC[Si](Cl)(Cl)Cl
CCCCC=1C=CC=CC1.C(=C)[Si](Cl)(Cl)Cl>>Cl[Si](Cl)(Cl)CCC1=C(C(=C(C(=C1CCCC)CC[Si](Cl)(Cl)Cl)CC[Si](Cl)(Cl)Cl)CC[Si](Cl)(Cl)Cl)CC[Si](Cl)(Cl)Cl
[CH2:7]=[CH:8][Si:9]([Cl:10])([Cl:31])[Cl:40].[CH3:1][CH2:2][CH2:3][CH2:4][c:5]1[cH:6][cH:14][cH:13][cH:29][cH:28]1>>[CH3:1][CH2:2][CH2:3][CH2:4][c:5]1[c:6]([CH2:7][CH2:8][Si:9]([Cl:10])([Cl:11])[Cl:12])[c:13]([CH2:14][CH2:15][Si:16]([Cl:17])([Cl:18])[Cl:19])[c:20]([CH2:21][CH2:22][Si:23]([Cl:24])([Cl:25])[Cl:26])[c:27...
C=C[Si](Cl)(Cl)Cl.CCCCc1ccccc1
CCCCc1c(CC[Si](Cl)(Cl)Cl)c(CC[Si](Cl)(Cl)Cl)c(CC[Si](Cl)(Cl)Cl)c(CC[Si](Cl)(Cl)Cl)c1CC[Si](Cl)(Cl)Cl
null
[Cl-].[Al+3].[Cl-].[Cl-]
null
Functional Group Addition
OtherReaction
84472cee9e18c6d957af5cab860570501d7c23416d2cb3f223907c01d09026ed
f39406e104622d7b50ce34fddb8ff597d6739d136261cbef91e2d935503b02ea
c1ccccc1
[CH2;D1;+0:1]=[CH;D2;+0:2]-[Si;H0;D4;+0:3](-[Cl;D1;H0:4])(-[Cl;H0;D1;+0:5])-[Cl;H0;D1;+0:6].[C:7]-[C:8]-[c;H0;D3;+0:9]1:[cH;D2;+0:10]:[cH;D2;+0:11]:[cH;D2;+0:12]:[cH;D2;+0:13]:[cH;D2;+0:14]:1>>[#14:15]-[C:16]-[CH2;D2;+0:13]-[c;H0;D3;+0:12]1:[c:17](-[C:18]):[c:19](-[CH2;D2;+0:10]-[CH2;D2;+0:11]-[#14:20](-[Cl;D1;H0:21])(...
102.2
[{"value": 2.68, "product": "Cl[Si](Cl)(Cl)CCC1=C(C(=C(C(=C1CCCC)CC[Si](Cl)(Cl)Cl)CC[Si](Cl)(Cl)Cl)CC[Si](Cl)(Cl)Cl)CC[Si](Cl)(Cl)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 102.2, "product": "Cl[Si](Cl)(Cl)CCC1=C(C(=C(C(=C1CCCC)CC[Si](Cl)(Cl)Cl)CC[Si](Cl)(Cl)Cl)CC[Si](Cl)(Cl)Cl)CC[Si](Cl)(Cl)Cl", "...
null
null
null
null
In the same apparatus and by the same procedure described in EXAMPLE 1, n-butylbenzene 0.86 g (6.40 mmol), vinyltrichlorosilane 5.17 g (32.00 mmol) and aluminum chloride 0.047 g (0.35 mmol) were reacted at 80° C. for 6 hours under a dry nitrogen atmosphere. Recrystallization of solid product from THF gave 6.16 g (yield...
10.6084/m9.figshare.5104873.v1
null
Vinyl.Silyl protective group
Silyl protective group.Silyl protective group.Silyl protective group.Silyl protective group.Silyl protective group
c1ccccc1
c1ccccc1
c1ccccc1
Other
[Cl-].[Al+3].[Cl-].[Cl-]
null
null
C=C[Si](Cl)(Cl)Cl.CCCCc1ccccc1>[Cl-].[Al+3].[Cl-].[Cl-]>CCCCc1c(CC[Si](Cl)(Cl)Cl)c(CC[Si](Cl)(Cl)Cl)c(CC[Si](Cl)(Cl)Cl)c(CC[Si](Cl)(Cl)Cl)c1CC[Si](Cl)(Cl)Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-2bfdd368208a447a97e7268f9780631d
N#CCO.O=C(O)CNCCO>>N#CCN(CCO)CC(=O)O
C(=O)(O)CNCCO.C(CO)#N>>C(=O)(O)CN(CC#N)CCO
O[CH2:3][C:2]#[N:1].[NH:4]([CH2:5][CH2:6][OH:7])[CH2:8][C:9](=[O:10])[OH:11]>>[N:1]#[C:2][CH2:3][N:4]([CH2:5][CH2:6][OH:7])[CH2:8][C:9](=[O:10])[OH:11]
N#CCO.O=C(O)CNCCO
N#CCN(CCO)CC(=O)O
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
f33a8d71b7dbaa463dcb87d1e5073e084c21a5fbc935ce82a22b6d65293f45d1
87693a475e46c41583976158ec46dcaf8be8cc05c5635654a6a68033770f8d5c
null
O-[CH2;D2;+0:1]-[C:2]#[N;D1;H0:3].[C:4]-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8](=[O;D1;H0:9])-[O;D1;H1:10]>>[C:4]-[C:5]-[N;H0;D3;+0:6](-[C:7]-[C:8](=[O;D1;H0:9])-[O;D1;H1:10])-[CH2;D2;+0:1]-[C:2]#[N;D1;H0:3]
null
[]
null
null
null
null
The hydrolysis of (I) with base gives N-carboxymethylamino-2-ethanol (II). Compound (II) is then reacted with additional glycolonitrile to form N-carboxymethyl-N-cyanomethylamino-2-ethanol (III). The molar ratio of (II) to glycolonitrile is generally about 1:1. In the above reactions, hydrogen cyanide and formaldehyde ...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Secondary amine
Tertiary amine
null
null
null
HO-
null
null
null
N#CCO.O=C(O)CNCCO>>N#CCN(CCO)CC(=O)O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-1fb9d43185c941be8156961fc5f37329
CC(=O)[O-].O=C1NC(=O)C(=Nc2c(O)[nH]c(=O)[nH]c2=O)C(=O)N1>>O=C(O)CN(CCO)CC(=O)O
O.C1(=C(NC(=O)NC1=O)[O-])N=C2C(=O)NC(=O)NC2=O.[NH4+].C1(=C(NC(=O)NC1=O)O)N=C2C(=O)NC(=O)NC2=O.N.C(C)(=O)[O-].[Na+]>>C(CO)N(CC(=O)O)CC(=O)O
[O-:3][C:7]([CH3:6])=[O:8].O=C1NC(=[O:12])N[C:10](=[O:11])[C:9]1=[N:5][c:4]1c(=O)[nH]c(=O)[nH][c:2]1[OH:1]>>[O:1]=[C:2]([OH:3])[CH2:4][N:5]([CH2:6][CH2:7][OH:8])[CH2:9][C:10](=[O:11])[OH:12]
CC(=O)[O-].O=C1NC(=O)C(=Nc2c(O)[nH]c(=O)[nH]c2=O)C(=O)N1
O=C(O)CN(CCO)CC(=O)O
null
[Cu](Cl)Cl.[Cu]
null
Acylation
OtherReaction
9872d15baae7386e238a714f7ab5cbb218e52e231f5916ade8e1ce865d9d8097
b67b6a3dad4b38052a431f993a20517f031191df13ef18b037a0b3d7fb52a40d
null
O=C1-N-C(=[O;H0;D1;+0:1])-N-[C;H0;D3;+0:2](=[O;D1;H0:3])-[C;H0;D3;+0:4]-1=[N;H0;D2;+0:5]-[c;H0;D3;+0:6]1:[c;H0;D3;+0:7](-[OH;D1;+0:8]):[nH]:c(=O):[nH]:c:1=O.[CH3;D1;+0:9]-[C;H0;D3;+0:10](-[O-;H0;D1:11])=[O;H0;D1;+0:12]>>[O;D1;H0:3]=[C;H0;D3;+0:2](-[OH;D1;+0:1])-[CH2;D2;+0:4]-[N;H0;D3;+0:5](-[CH2;D2;+0:6]-[C;H0;D3;+0:7]...
null
[]
null
null
null
null
Copper titration value is used to measure the extent of biodegradation of the chelating agents during the procedure. Titration is performed using ammonium purpurate (indicator for complexometric titration, commercially available from Aldrich Chemical Co., Inc. under the trade designation Murexide) as the indicator at a...
10.6084/m9.figshare.5104873.v1
null
Urea.Substituted imine.Unsubstituted dicarboximide.Unsubstituted dicarboximide.Aromatic alcohol
Carboxylic acid.Carboxylic acid.Primary alcohol.Tertiary amine
C1CNCNC1.c1cncnc1
null
null
Other
[Cu](Cl)Cl.[Cu]
null
null
CC(=O)[O-].O=C1NC(=O)C(=Nc2c(O)[nH]c(=O)[nH]c2=O)C(=O)N1>[Cu](Cl)Cl.[Cu]>O=C(O)CN(CCO)CC(=O)O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-2ed9fcf75bbf4af59779e91e6297c949
O=Cc1ccc(Cl)c(Cl)c1.[C-]#N>>N#CC(O)c1ccc(Cl)c(Cl)c1
[C-]#N.[K+].ClC=1C=C(C=O)C=CC1Cl>>ClC=1C=C(C=CC1Cl)C(C#N)O
[CH:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([Cl:9])[c:10]([Cl:11])[cH:12]1.[N:1]#[C-:2]>>[N:1]#[C:2][CH:3]([OH:4])[c:5]1[cH:6][cH:7][c:8]([Cl:9])[c:10]([Cl:11])[cH:12]1
O=Cc1ccc(Cl)c(Cl)c1.[C-]#N
N#CC(O)c1ccc(Cl)c(Cl)c1
null
null
O
C-C Coupling
OtherReaction
236cd56a92cf15f00d53dce2793575c5ed7c3ec173ebae4a1233543c0db3ac9d
68cad6670aea61b0290696d3ddb6b46e4783b1c98982f76fc6b06e18aa6719c1
c1ccccc1
[C-;H0;D1:1]#[N;D1;H0:2].[O;H0;D1;+0:3]=[CH;D2;+0:4]-[c:5](:[c:6]):[c:7]>>[N;D1;H0:2]#[C;H0;D2;+0:1]-[CH;D3;+0:4](-[OH;D1;+0:3])-[c:5](:[c:6]):[c:7]
100.5
[{"value": 100.5, "product": "ClC=1C=C(C=CC1Cl)C(C#N)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
25 g of 3,4-dichlorobenzaldehyde are added to a solution of 32.5 g of Na2S2O5 in 100 ml of water and the mixture is heated at 40°-45° C. for 1 hour. After one night at room temperature, the reaction mixture is cooled and a solution of 19.5 g of KCN in 40 ml of water is added slowly. After stirring for 30 minutes at RT,...
10.6084/m9.figshare.5104873.v1
null
Aldehyde
Nitrile.Secondary alcohol
null
null
c1ccccc1
null
O
null
0.5
O=Cc1ccc(Cl)c(Cl)c1.[C-]#N>O>N#CC(O)c1ccc(Cl)c(Cl)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-f2cd038ec84e4a03a81609c6e7029c63
CNCCO.O=Cc1ccc(Cl)c(Cl)c1>>CN(CCO)C(C#N)c1ccc(Cl)c(Cl)c1
ClC=1C=C(C=O)C=CC1Cl.C(#N)[Si](C)(C)C.CNCCO>>ClC=1C=C(C=CC1Cl)C(C#N)N(C)CCO
[CH3:1][NH:2][CH2:3][CH2:4][OH:5].O=[CH:6][c:9]1[cH:10][cH:11][c:12]([Cl:13])[c:14]([Cl:15])[cH:16]1>>[CH3:1][N:2]([CH2:3][CH2:4][OH:5])[CH:6]([C:7]#[N:8])[c:9]1[cH:10][cH:11][c:12]([Cl:13])[c:14]([Cl:15])[cH:16]1
CNCCO.O=Cc1ccc(Cl)c(Cl)c1
CN(CCO)C(C#N)c1ccc(Cl)c(Cl)c1
null
[I-].[Zn+2].[I-]
CO
Heteroatom Alkylation and Arylation
OtherReaction
65895308b5f67b585ddaa37f306e495e36985cf3c70224ad6c8aa7852833472c
860dd54cb9329ea0e96b0cf04a71152378c5b5aab7f54c5a6ec1d7b1b585ad63
c1ccccc1
O=[CH;D2;+0:1]-[c:2](:[c:3]):[c:4].[C:5]-[C:6]-[NH;D2;+0:7]-[C;D1;H3:8]>>[C:5]-[C:6]-[N;H0;D3;+0:7](-[C;D1;H3:8])-[CH;D3;+0:1](-[C:9]#[N;D1;H0:10])-[c:2](:[c:3]):[c:4]
null
[]
null
null
15
MINUTE
A mixture of 10 g of 3,4-dichlorobenzaldehyde and 9.5 ml of cyanotrimethylsilane is cooled in an ice bath, 0.01 g of zinc iodide is added and the mixture is stirred for 15 minutes at RT. A solution of 4.5 g of 2-(methylamino)ethanol in 50 ml of MeOH is then added and the reaction mixture is heated at 60° C. for 2 hours...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Secondary amine
Nitrile.Tertiary amine
null
null
c1ccccc1
HO-
[I-].[Zn+2].[I-].CO
null
0.25
CNCCO.O=Cc1ccc(Cl)c(Cl)c1>[I-].[Zn+2].[I-].CO>CN(CCO)C(C#N)c1ccc(Cl)c(Cl)c1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-2ea15a5f5b1a44b1851d5776c77eecc6
BrCc1ccccc1.C1CCOC1.CCOCC.N#CC1CCNCC1>>N#CC1(Cc2ccccc2)CCN(Cc2ccccc2)CC1
C(C1=CC=CC=C1)Br.C(C)(C)[N-]C(C)C.[Li+].CCOCC.C(#N)C1CCNCC1.C1CCOC1>>C(C1=CC=CC=C1)N1CCC(CC1)(C#N)CC1=CC=CC=C1
Br[CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1.O1[CH2:7][CH2:6][CH2:5][CH2:10]1.C[CH2:4]O[CH2:8][CH3:9].[N:1]#[C:2][CH:3]1[CH2:11][CH2:12][NH:13][CH2:21][CH2:22]1>>[N:1]#[C:2][C:3]1([CH2:4][c:5]2[cH:6][cH:7][cH:8][cH:9][cH:10]2)[CH2:11][CH2:12][N:13]([CH2:14][c:15]2[cH:16][cH:17][cH:18][cH:19][cH:20]2)[CH2:21][C...
BrCc1ccccc1.C1CCOC1.CCOCC.N#CC1CCNCC1
N#CC1(Cc2ccccc2)CCN(Cc2ccccc2)CC1
null
null
C1CCCCC1
Aromatic Heterocycle Formation
OtherReaction
d921e7522bf8776c1b967ac12f340ec2076285c08bd5b01e4d9da413aba257b9
6af2cbbe2292f8983804f000c10af2ef039866a3ad561dd0c7834578d992cd0f
c1ccc(CC2CCN(Cc3ccccc3)CC2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].C-[CH2;D2;+0:5]-O-[CH2;D2;+0:6]-[CH3;D1;+0:7].O1-[CH2;D2;+0:8]-[CH2;D2;+0:9]-[CH2;D2;+0:10]-[CH2;D2;+0:11]-1.[N;D1;H0:12]#[C:13]-[CH;D3;+0:14]1-[C:15]-[C:16]-[NH;D2;+0:17]-[C:18]-[C:19]-1>>[N;D1;H0:12]#[C:13]-[C;H0;D4;+0:14]1(-[CH2;D2;+0:5]-[c;H0;D3;+0:9]2:[cH;D2;+0:8]:[cH;D2;+0:7]:...
null
[]
-50
CELSIUS
30
MINUTE
A solution of 15 g of 4-cyanopiperidine in 250 ml of THF is cooled to -50° C., 190 ml of a 1.5M solution of lithium diisopropylamide in cyclohexane are added dropwise and the mixture is stirred for 30 minutes at -50° C. 34 ml of benzyl bromide are then added and the mixture is stirred for 3 hours after the temperature ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ether.Ether.Secondary amine
Tertiary amine
C1CCOC1.C1CCNCC1
c1ccccc1.C1CC[NH]CC1
c1ccccc1.C1CC[NH]CC1.c1ccccc1
HBr
C1CCCCC1
-50
0.5
BrCc1ccccc1.C1CCOC1.CCOCC.N#CC1CCNCC1>C1CCCCC1>N#CC1(Cc2ccccc2)CCN(Cc2ccccc2)CC1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-c7a3ca41e01d4efebb1bd0e9b36a8939
CN(CC(OCCOC1CCCCO1)c1ccc(Cl)c(Cl)c1)C(=O)OC(C)(C)C>>CN(CC(OCCO)c1ccc(Cl)c(Cl)c1)C(=O)OC(C)(C)C
C1(=CC=C(C=C1)S(=O)(=O)[O-])C.[NH+]1=CC=CC=C1.CN(CC(OCCOC1OCCCC1)C1=CC(=C(C=C1)Cl)Cl)C(=O)OC(C)(C)C>>CN(CC(OCCO)C1=CC(=C(C=C1)Cl)Cl)C(=O)OC(C)(C)C
C1CCC([O:8][CH2:7][CH2:6][O:5][CH:4]([CH2:3][N:2]([CH3:1])[C:17](=[O:18])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])[c:9]2[cH:10][cH:11][c:12]([Cl:13])[c:14]([Cl:15])[cH:16]2)OC1>>[CH3:1][N:2]([CH2:3][CH:4]([O:5][CH2:6][CH2:7][OH:8])[c:9]1[cH:10][cH:11][c:12]([Cl:13])[c:14]([Cl:15])[cH:16]1)[C:17](=[O:18])[O:19][C:20]([C...
CN(CC(OCCOC1CCCCO1)c1ccc(Cl)c(Cl)c1)C(=O)OC(C)(C)C
CN(CC(OCCO)c1ccc(Cl)c(Cl)c1)C(=O)OC(C)(C)C
null
null
CO
Reduction
Ether cleavage to primary alcohol
69ac283008defddd09d640f7879e86f66dd29371b5c835a2facf24163ef14e9f
a4561cbdd42f56679299e19ea8b11070a39a15f6a95fb8a877e677f11b7ff57f
c1ccccc1
[C:1]-[C:2]-[O;H0;D2;+0:3]-C1-C-C-C-C-O-1>>[C:1]-[C:2]-[OH;D1;+0:3]
100.9
[{"value": 100.9, "product": "CN(CC(OCCO)C1=CC(=C(C=C1)Cl)Cl)C(=O)OC(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
0.56 g of pyridinium paratoluenesulfonate is added to a solution of 10 g of the compound obtained in EXAMPLE 8, step C), in 100 ml of MeOH and the reaction mixture is refluxed for 1 hour 15 minutes. It is concentrated under vacuum and the residue is taken up with ether, washed with water and with a buffer solution of p...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether
Primary alcohol
C1CCOCC1
null
c1ccccc1
HO-
CO
null
null
CN(CC(OCCOC1CCCCO1)c1ccc(Cl)c(Cl)c1)C(=O)OC(C)(C)C>CO>CN(CC(OCCO)c1ccc(Cl)c(Cl)c1)C(=O)OC(C)(C)C
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-1ef8b43a3b744c0190064171c4bf7822
CCC(=O)Cl.CCCl.CCN(CC)CC.CN(CC(OCCN1CCC(O)(c2ccccc2)CC1)c1ccc(Cl)c(Cl)c1)C(=O)OCc1ccccc1.Cl>>CCC(=O)OC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)OCc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1.CCC(=O)OC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)OCc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1.Cl.Cl.O
CCCl.C(C)N(CC)CC.C(CC)(=O)Cl.Cl.OC1(CCN(CC1)CCOC(CN(C(=O)OCC1=CC=CC=C1)C)C1=CC(=C(C=C1)Cl)Cl)C1=CC=CC=C1>>O.Cl.C1(=CC=CC=C1)C1(CCN(CC1)CCOC(CN(C(=O)OCC1=CC=CC=C1)C)C1=CC(=C(C=C1)Cl)Cl)OC(CC)=O.C1(=CC=CC=C1)C1(CCN(CC1)CCOC(CN(C)C(=O)OCC1=CC=CC=C1)C1=CC(=C(C=C1)Cl)Cl)OC(CC)=O.Cl
[CH3:43][CH2:44][C:45](=[O:46])[Cl:85].[CH3:1][CH2:2][Cl:81].[CH2:3]([N:21]([CH2:62][CH3:61])[CH2:68][CH3:69])[CH3:77].[O:4]=[C:65]([O:25][CH2:26][c:27]1[cH:28][cH:29][cH:30][cH:31][cH:32]1)[N:63]([CH2:20][CH:19]([O:18][CH2:17][CH2:16][N:15]1[CH2:14][CH2:13][C:6]([OH:5])([c:7]2[cH:8][cH:9][cH:10][cH:11][cH:12]2)[CH2:42...
CCC(=O)Cl.CCCl.CCN(CC)CC.CN(CC(OCCN1CCC(O)(c2ccccc2)CC1)c1ccc(Cl)c(Cl)c1)C(=O)OCc1ccccc1.Cl
CCC(=O)OC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)OCc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1.CCC(=O)OC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)OCc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1.Cl.Cl.O
null
null
C(Cl)Cl
Aromatic Heterocycle Formation
OtherReaction
57073be6faedcc2d5bb06d1e6b9e9ffa3359ccf5259f4ee5b3dbebbb1e979158
9c547aac983238d738640532f12fa6284b51a1c211c6d3e928557125ecee582a
O=C(NCC(OCCN1CCC(c2ccccc2)CC1)c1ccccc1)OCc1ccccc1.O=C(NCC(OCCN1CCC(c2ccccc2)CC1)c1ccccc1)OCc1ccccc1
[#8:1]-[C:2](-[c:3])-[CH2;D2;+0:4]-[N;H0;D3;+0:5](-[C;D1;H3:6])-[C;H0;D3;+0:7](=[O;H0;D1;+0:8])-[O;H0;D2;+0:9]-[C:10]-[c:11].[C:12]-[C:13](-[OH;D1;+0:14])(-[c:15])-[C:16].[C;D1;H3:17]-[CH2;D2;+0:18]-[Cl;H0;D1;+0:19].[C;D1;H3:20]-[C:21]-[C;H0;D3;+0:22](-[Cl;H0;D1;+0:23])=[O;D1;H0:24].[CH3;D1;+0:25]-[CH2;D2;+0:26]-[N;H0;...
null
[]
null
null
15
MINUTE
670 mg of the compound obtained in EXAMPLE 9 are dissolved in 10 ml of methylene chloride, and 0.2 ml of triethylamine and 0.2 ml of propionyl chloride are then added, with stirring. After 15 minutes, the reaction mixture is washed with water and then with 10% Na2CO3 solution and the organic phase is dried over MgSO4 a...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary halide.Carbamic ester.Ether.Tertiary alcohol.Tertiary amine
Aromatic halide.Aromatic halide.Carbamic ester.Carbamic ester.Ester.Ester.Ether.Ether.Ether.Tertiary amine
null
c1ccccc1.C1CC[NH]CC1.c1ccccc1.c1ccccc1
c1ccccc1.C1CC[NH]CC1.c1ccccc1.c1ccccc1.c1ccccc1.C1CC[NH]CC1.c1ccccc1.c1ccccc1
Other
C(Cl)Cl
null
0.25
CCC(=O)Cl.CCCl.CCN(CC)CC.CN(CC(OCCN1CCC(O)(c2ccccc2)CC1)c1ccc(Cl)c(Cl)c1)C(=O)OCc1ccccc1.Cl>C(Cl)Cl>CCC(=O)OC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)OCc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1.CCC(=O)OC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)OCc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1.Cl.Cl.O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-7d504e6d31bb4728a49a96e042f2ee0f
CNCC(OCCN1CCC(NC(C)=O)(c2ccccc2)CC1)c1ccc(Cl)c(Cl)c1.O=C(Cl)OCc1ccccc1>>CC(=O)NC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)OCc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1
CCCl.C(C)N(CC)CC.Cl.Cl.C(C)(=O)NC1(CCN(CC1)CCOC(CNC)C1=CC(=C(C=C1)Cl)Cl)C1=CC=CC=C1.ClC(=O)OCC1=CC=CC=C1>>Cl.C(C)(=O)NC1(CCN(CC1)CCOC(CN(C(=O)OCC1=CC=CC=C1)C)C1=CC(=C(C=C1)Cl)Cl)C1=CC=CC=C1
[CH3:1][C:2](=[O:3])[NH:4][C:5]1([c:6]2[cH:7][cH:8][cH:9][cH:10][cH:11]2)[CH2:12][CH2:13][N:14]([CH2:15][CH2:16][O:17][CH:18]([CH2:19][NH:20][CH3:21])[c:32]2[cH:33][cH:34][c:35]([Cl:36])[c:37]([Cl:38])[cH:39]2)[CH2:40][CH2:41]1.Cl[C:22](=[O:23])[O:24][CH2:25][c:26]1[cH:27][cH:28][cH:29][cH:30][cH:31]1>>[CH3:1][C:2](=[O...
CNCC(OCCN1CCC(NC(C)=O)(c2ccccc2)CC1)c1ccc(Cl)c(Cl)c1.O=C(Cl)OCc1ccccc1
CC(=O)NC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)OCc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1
null
null
C(Cl)Cl
Protection
N-alkylation of secondary amines with alkyl halides
496a200c7c2fc7c000296e03cda40efb8e258ccaeb02fa999285bf74ddc49346
d86dc1e6d0e089b3444b62ddfcf4c4822bdac4b60e628553036562518c29adcd
O=C(NCC(OCCN1CCC(c2ccccc2)CC1)c1ccccc1)OCc1ccccc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C:4].[C:5]-[C:6]-[NH;D2;+0:7]-[C;D1;H3:8]>>[C:5]-[C:6]-[N;H0;D3;+0:7](-[C;D1;H3:8])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C:4]
null
[]
0
CELSIUS
null
null
0.41 ml of triethylamine is added to a solution of 0.5 g of the compound obtained in EXAMPLE 11, step B), in 10 ml of DCM, the mixture is then cooled to 0° C. and 0.14 ml of benzyl chloroformate is added dropwise. The reaction mixture is washed twice with water, dried over MgSO4 and concentrated under vacuum. The resid...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Ether.Secondary amine
Carbamic ester
null
null
c1ccccc1.C1CC[NH]CC1.c1ccccc1.c1ccccc1
HCl
C(Cl)Cl
0
null
CNCC(OCCN1CCC(NC(C)=O)(c2ccccc2)CC1)c1ccc(Cl)c(Cl)c1.O=C(Cl)OCc1ccccc1>C(Cl)Cl>CC(=O)NC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)OCc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-b505007df247456aa881670aca334437
CCCl.CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C.CNCC(OCCN1CCC(NC(C)=O)(c2ccccc2)CC1)c1ccc(Cl)c(Cl)c1.Cl.O=C(O)Cc1ccccc1>>CC(=O)NC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)Cc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1.CC(=O)NC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)Cc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1.Cl.O
CCCl.F[P-](F)(F)(F)(F)F.N1(N=NC2=C1C=CC=C2)O[P+](N(C)C)(N(C)C)N(C)C.Cl.Cl.C(C)(=O)NC1(CCN(CC1)CCOC(CNC)C1=CC(=C(C=C1)Cl)Cl)C1=CC=CC=C1.C1(=CC=CC=C1)CC(=O)O>>O.Cl.C(C)(=O)NC1(CCN(CC1)CCOC(CN(C(=O)CC1=CC=CC=C1)C)C1=CC(=C(C=C1)Cl)Cl)C1=CC=CC=C1.C(C)(=O)NC1(CCN(CC1)CCOC(CN(C)C(=O)CC1=CC=CC=C1)C1=CC(=C(C=C1)Cl)Cl)C1=CC=CC=C...
[CH2:24]([CH3:25])[Cl:37].n1[n:44][c:45]2[cH:38][cH:36][cH:34][cH:51][c:46]2[n:54]1[O:43][P+](N([CH3:18])[CH3:31])(N([CH3:19])[CH3:41])[N:20]([CH3:21])[CH3:22].[CH3:1][C:2](=[O:3])[NH:4][C:5]1([c:6]2[cH:7][cH:8][cH:9][cH:10][cH:11]2)[CH2:12][CH2:13][N:14]([CH2:15][CH2:16][O:17][CH:58]([CH2:59][NH:60][CH3:61])[c:71]2[cH...
CCCl.CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C.CNCC(OCCN1CCC(NC(C)=O)(c2ccccc2)CC1)c1ccc(Cl)c(Cl)c1.Cl.O=C(O)Cc1ccccc1
CC(=O)NC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)Cc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1.CC(=O)NC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)Cc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1.Cl.O
null
null
C(Cl)Cl.C(C)N(CC)CC
Aromatic Heterocycle Formation
OtherReaction
fbc1bf9e9850da35158abf121e62080f85848c864fb1d301d05d27533a5f2ea4
6f50c022d88226844c1ec51d75aba7a23d86bfccd362a324d39ca7a98259aa0c
O=C(Cc1ccccc1)NCC(OCCN1CCC(c2ccccc2)CC1)c1ccccc1.O=C(Cc1ccccc1)NCC(OCCN1CCC(c2ccccc2)CC1)c1ccccc1
[C;D1;H3:1]-[N;H0;D3;+0:2](-[CH3;D1;+0:3])-[P+](-[O;H0;D2;+0:4]-[n;H0;D3;+0:5]1:n:[n;H0;D2;+0:6]:[c;H0;D3;+0:7]2:[cH;D2;+0:8]:[cH;D2;+0:9]:[cH;D2;+0:10]:[cH;D2;+0:11]:[c;H0;D3;+0:12]:2:1)(-N(-[CH3;D1;+0:13])-[CH3;D1;+0:14])-N(-[CH3;D1;+0:15])-[CH3;D1;+0:16].[CH3;D1;+0:17]-[CH2;D2;+0:18]-[Cl;H0;D1;+0:19].[C:20]-[C:21]-[...
null
[]
null
null
null
null
0.46 ml of triethylamine and then 0.5 g of BOP are added to a mixture of 0.5 g of the compound obtained in EXAMPLE 11, step B), 0.127 g of phenylacetic acid and 10 ml of DCM. The resulting mixture is concentrated under vacuum and the residue is taken up with AcOEt, washed with water, with 1N NaOH solution and with satu...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Carboxylic acid.Ether.Secondary amine.Tertiary amine.Tertiary amine.Tertiary amine
Aromatic halide.Aromatic halide.Ether.Ether.Secondary amide.Tertiary amide.Tertiary amide.Tertiary amine
c1ccc2[nH]nnc2c1
c1ccccc1.c1ccccc1.c1ccccc1.C1CC[NH]CC1
c1ccccc1.C1CC[NH]CC1.c1ccccc1.c1ccccc1.c1ccccc1.C1CC[NH]CC1.c1ccccc1.c1ccccc1
null
C(Cl)Cl.C(C)N(CC)CC
null
null
CCCl.CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C.CNCC(OCCN1CCC(NC(C)=O)(c2ccccc2)CC1)c1ccc(Cl)c(Cl)c1.Cl.O=C(O)Cc1ccccc1>C(Cl)Cl.C(C)N(CC)CC>CC(=O)NC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)Cc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1.CC(=O)NC1(c2ccccc2)CCN(CCOC(CN(C)C(=O)Cc2ccccc2)c2ccc(Cl)c(Cl)c2)CC1.Cl.O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-9f25fd50f39249598d47f6ff669d7346
O=P(Cl)(Cl)Cl.Oc1nc(Cc2ccc(F)cc2)ncc1F>>Fc1ccc(Cc2ncc(F)c(Cl)n2)cc1
FC=1C(=NC(=NC1)CC1=CC=C(C=C1)F)O.P(=O)(Cl)(Cl)Cl>>ClC1=NC(=NC=C1F)CC1=CC=C(C=C1)F
O=P(Cl)(Cl)[Cl:13].O[c:12]1[c:10]([F:11])[cH:9][n:8][c:7]([CH2:6][c:5]2[cH:4][cH:3][c:2]([F:1])[cH:16][cH:15]2)[n:14]1>>[F:1][c:2]1[cH:3][cH:4][c:5]([CH2:6][c:7]2[n:8][cH:9][c:10]([F:11])[c:12]([Cl:13])[n:14]2)[cH:15][cH:16]1
O=P(Cl)(Cl)Cl.Oc1nc(Cc2ccc(F)cc2)ncc1F
Fc1ccc(Cc2ncc(F)c(Cl)n2)cc1
null
null
null
Functional Group Interconversion
Alcohol to chloride_POCl3_ortho
c34cc3a735ba90a6ebc3a31af86c6a0085713d9dcab569055caa3b8d444bb07d
e71580a8ffadb7b2717ecd7d68c1d3c0ca161ba5e6a787a49dad5a1359adc993
c1ccc(Cc2ncccn2)cc1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4](-[C:5]):[#7;a:6]:[c:7]:[c:8]:1-[F;D1;H0:9]>>[C:5]-[c:4]1:[#7;a:3]:[c;H0;D3;+0:2](-[Cl;H0;D1;+0:1]):[c:8](-[F;D1;H0:9]):[c:7]:[#7;a:6]:1
90
[{"value": 90.0, "product": "ClC1=NC(=NC=C1F)CC1=CC=C(C=C1)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 1.93 g (8.7 mmol) of 5-fluoro-2-(4-fluorobenzyl)-4-hydroxypyrimidine, from Step 1, and 15 mL of phosphorus oxychloride was heated in an oil bath at 90° C. for 1.5 hours and then concentrated in vacuo. The residue was triturated with 75 mL of ice water and the aqueous mixture was adjusted to pH 8-9 by the a...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Aromatic halide
c1cncnc1
c1cncnc1
c1ccccc1.c1cncnc1
HCl
null
null
null
O=P(Cl)(Cl)Cl.Oc1nc(Cc2ccc(F)cc2)ncc1F>>Fc1ccc(Cc2ncc(F)c(Cl)n2)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-9f9fb1d3a7e54201b973e3a877894221
CN1CCNCC1.Fc1ccc(Cc2ncc(F)c(Cl)n2)cc1>>CN1CCN(c2nc(Cc3ccc(F)cc3)ncc2F)CC1
ClC1=NC(=NC=C1F)CC1=CC=C(C=C1)F.CN1CCNCC1>>FC=1C(=NC(=NC1)CC1=CC=C(C=C1)F)N1CCN(CC1)C
[CH3:1][N:2]1[CH2:3][CH2:4][NH:5][CH2:21][CH2:22]1.Cl[c:6]1[n:7][c:8]([CH2:9][c:10]2[cH:11][cH:12][c:13]([F:14])[cH:15][cH:16]2)[n:17][cH:18][c:19]1[F:20]>>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([c:6]2[n:7][c:8]([CH2:9][c:10]3[cH:11][cH:12][c:13]([F:14])[cH:15][cH:16]3)[n:17][cH:18][c:19]2[F:20])[CH2:21][CH2:22]1
CN1CCNCC1.Fc1ccc(Cc2ncc(F)c(Cl)n2)cc1
CN1CCN(c2nc(Cc3ccc(F)cc3)ncc2F)CC1
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
a9178a48f510c186744480d82f1e9a1a3beb7a148197ba9ff5ade9c935d3afea
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
c1ccc(Cc2nccc(N3CCNCC3)n2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5]:[c:6]:1-[F;D1;H0:7].[#7:8]1-[C:9]-[C:10]-[NH;D2;+0:11]-[C:12]-[C:13]-1>>[F;D1;H0:7]-[c:6]1:[c:5]:[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1]:1-[N;H0;D3;+0:11]1-[C:10]-[C:9]-[#7:8]-[C:13]-[C:12]-1
96.9
[{"value": 95.0, "product": "FC=1C(=NC(=NC1)CC1=CC=C(C=C1)F)N1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 96.9, "product": "FC=1C(=NC(=NC1)CC1=CC=C(C=C1)F)N1CCN(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1.5
HOUR
A mixture of 0.48 g (2 mmol) of 4-chloro-5-fluoro-2-(4-fluorobenzyl)-pyrimidine from Step 2 and 1.53 mL (14 mmol) of 4-methylpiperazine in 10 mL of methylene chloride was stirred at ambient temperature for 1.5 hours. The reaction mixture was concentrated in vacuo and the residue was dissolved in methylene chloride. The...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1C[NH]CCN1.c1cncnc1
C1C[NH]CC[NH]1.c1cncnc1
C1C[NH]CC[NH]1.c1cncnc1.c1ccccc1
HCl
C(Cl)Cl
null
1.5
CN1CCNCC1.Fc1ccc(Cc2ncc(F)c(Cl)n2)cc1>C(Cl)Cl>CN1CCN(c2nc(Cc3ccc(F)cc3)ncc2F)CC1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-c692bc85106744069adc7052796b1100
CCC[C@H](NC(=O)OC(C)(C)C)C(=O)NC1CCNC1.CCOC(=O)c1ccc2cc(Cl)ccn2c1=O>>CCC[C@H](N)C(=O)NC1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)C1
ClC=1C=CN2C(C(=CC=C2C1)C(=O)OCC)=O.NC1CN(CC1)CC1=CC=CC=C1.C(C)(C)(C)OC(=O)N[C@@H](CCC)C(=O)O.C(=O)(OC(C)(C)C)N[C@@H](CCC)C(=O)NC1CNCC1.ON1C(CCC1=O)=O>>N[C@@H](CCC)C(=O)NC1CN(CC1)C=1C=CN2C(C(=CC=C2C1)C(=O)O)=O
CC(C)(C)OC(=O)[NH:5][C@@H:4]([CH2:3][CH2:2][CH3:1])[C:6](=[O:7])[NH:8][CH:9]1[CH2:10][CH2:11][NH:12][CH2:27]1.CC[O:22][C:20]([c:19]1[c:17](=[O:18])[n:16]2[cH:15][cH:14][c:13](Cl)[cH:26][c:25]2[cH:24][cH:23]1)=[O:21]>>[CH3:1][CH2:2][CH2:3][C@H:4]([NH2:5])[C:6](=[O:7])[NH:8][CH:9]1[CH2:10][CH2:11][N:12]([c:13]2[cH:14][cH...
CCC[C@H](NC(=O)OC(C)(C)C)C(=O)NC1CCNC1.CCOC(=O)c1ccc2cc(Cl)ccn2c1=O
CCC[C@H](N)C(=O)NC1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)C1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
3372844e8874019375346d6c944b99477e0efc73838c38032f67789541cb28f9
5c530bc185fdf54956090e5ff31b4625247366cd666dcae789cfd53ed04cb8aa
O=c1cccc2cc(N3CCCC3)ccn12
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C:3])-[C:4](=[O;D1;H0:5])-[#7:6]-[C:7]1-[C:8]-[C:9]-[NH;D2;+0:10]-[C:11]-1.C-C-[O;H0;D2;+0:12]-[C:13](=[O;D1;H0:14])-[c:15]:[c:16]:[#7;a:17]1:[c:18]:[c:19]:[c;H0;D3;+0:20](-Cl):[c:21]:[c:22]:1:[c:23]>>[C:3]-[C:2](-[NH2;D1;+0:1])-[C:4](=[O;D1;H0:5])-[#7:6]-[C:7]1-[C:8]-[C:9]-[N;H...
null
[]
null
null
null
null
3-Amino-1-benzylpyrrolidine (I. Sumio and T. Matsuo, Japanese Kokai JP 5328161, published Mar. 16, 1978) is coupled to N-t-butoxycarbonyl norvaline (Boc-nVal) using conventional N-hydroxysuccinimide coupling procedures. The 1-benzyl group is removed by hydrogenolysis in methanol using palladium on carbon catalyst. The ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Carbamic ester.Ester.Ether.Secondary amine.Boc
Carboxylic acid.Primary amine.Tertiary amine
C1CCNC1.c1cn2ccccc2cc1
C1CC[NH]C1.c1cn2ccccc2cc1
C1CC[NH]C1.c1cn2ccccc2cc1
HCl
null
null
null
CCC[C@H](NC(=O)OC(C)(C)C)C(=O)NC1CCNC1.CCOC(=O)c1ccc2cc(Cl)ccn2c1=O>>CCC[C@H](N)C(=O)NC1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)C1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-d1417262cbeb4dcfb27be135b8b405b2
CCOC(=O)c1ccc2cc(Cl)ccn2c1=O.CN1CCNCC1>>CCOC(=O)c1ccc2cc(N3CCN(C)CC3)ccn2c1=O
ClC=1C=CN2C(C(=CC=C2C1)C(=O)OCC)=O.ClC=1C=CN2C(C(=CC=C2C1)C(=O)OCC)=O.CN1CCNCC1>>CN1CCN(CC1)C=1C=CN2C(C(=CC=C2C1)C(=O)OCC)=O
Cl[c:11]1[cH:10][c:9]2[cH:8][cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:22](=[O:23])[n:21]2[cH:20][cH:19]1.[NH:12]1[CH2:13][CH2:14][N:15]([CH3:16])[CH2:17][CH2:18]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][cH:8][c:9]2[cH:10][c:11]([N:12]3[CH2:13][CH2:14][N:15]([CH3:16])[CH2:17][CH2:18]3)[cH:19][cH:20][n:21]2[c...
CCOC(=O)c1ccc2cc(Cl)ccn2c1=O.CN1CCNCC1
CCOC(=O)c1ccc2cc(N3CCN(C)CC3)ccn2c1=O
null
null
N1=CC=CC=C1
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
d1eef4f8c0aa68dde2b04e6a19bf2997a325e5677cab2bf9db6ffa7b61f605c2
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=c1cccc2cc(N3CCNCC3)ccn12
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3](:[c:4]):[#7;a:5](:[c:6]):[c:7]:[c:8]:1.[#7:9]1-[C:10]-[C:11]-[NH;D2;+0:12]-[C:13]-[C:14]-1>>[c:6]:[#7;a:5]1:[c:7]:[c:8]:[c;H0;D3;+0:1](-[N;H0;D3;+0:12]2-[C:11]-[C:10]-[#7:9]-[C:14]-[C:13]-2):[c:2]:[c:3]:1:[c:4]
106.8
[{"value": 106.8, "product": "CN1CCN(CC1)C=1C=CN2C(C(=CC=C2C1)C(=O)OCC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
null
null
Ethyl 8-chloro-4H-quinolizin-4-one-3-carboxylate (755 mg, 3.0 mmol), the product of Step 3 of Example 58, was suspended in 12 mL of dry pyridine under a nitrogen atmosphere. To the resultant solution was added 6.0 mL (6.0 mmol) of N-methylpiperazine and the reaction mixture was heated at 70° C. for 8 hours. The reactio...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
c1cn2ccccc2cc1.C1CNCC[NH]1
c1cn2ccccc2cc1.C1C[NH]CC[NH]1
c1cn2ccccc2cc1.C1C[NH]CC[NH]1
HCl
N1=CC=CC=C1
70
null
CCOC(=O)c1ccc2cc(Cl)ccn2c1=O.CN1CCNCC1>N1=CC=CC=C1>CCOC(=O)c1ccc2cc(N3CCN(C)CC3)ccn2c1=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-9f579710cd264918b47252784f610bcf
CCOC(=O)c1ccc2cc(N3CCN(C)CC3)ccn2c1=O>>CN1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)CC1
Cl.[OH-].[Na+].CN1CCN(CC1)C=1C=CN2C(C(=CC=C2C1)C(=O)OCC)=O>>Cl.CN1CCN(CC1)C=1C=CN2C(C(=CC=C2C1)C(=O)O)=O
CC[O:15][C:13]([c:12]1[c:10](=[O:11])[n:9]2[cH:8][cH:7][c:6]([N:5]3[CH2:4][CH2:3][N:2]([CH3:1])[CH2:21][CH2:20]3)[cH:19][c:18]2[cH:17][cH:16]1)=[O:14]>>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([c:6]2[cH:7][cH:8][n:9]3[c:10](=[O:11])[c:12]([C:13](=[O:14])[OH:15])[cH:16][cH:17][c:18]3[cH:19]2)[CH2:20][CH2:21]1
CCOC(=O)c1ccc2cc(N3CCN(C)CC3)ccn2c1=O
CN1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)CC1
null
null
C1CCOC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=c1cccc2cc(N3CCNCC3)ccn12
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
null
[]
75
CELSIUS
8
HOUR
A mixture of 0.865 g (2.75 mmol) of ethyl 8-(4-methylpiperazin-1-yl)-4H-quinolizin-4-one-3-carboxylate, from Step 1, in 12 mL of THF and 16.5 mL of a 0.5N aqueous solution of sodium hydroxide was heated, with stirring, at 75° C. for 8 hours. The THF was removed from the reaction mixture by distillation during the react...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1C[NH]CC[NH]1.c1cn2ccccc2cc1
Other
C1CCOC1
75
8
CCOC(=O)c1ccc2cc(N3CCN(C)CC3)ccn2c1=O>C1CCOC1>CN1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)CC1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-05fc3ca2347f436aa6a5c4b9b479ce81
CCI.Cc1cc(Cl)ccn1>>CCCc1cc(Cl)ccn1
[Li+].CC(C)[N-]C(C)C.[Li+].CC(C)[N-]C(C)C.CCCCCC.[N+](=O)(O)[O-].C(C)I.ClC1=CC(=NC=C1)C>>ClC1=CC(=NC=C1)CCC
I[CH2:2][CH3:1].[CH3:3][c:4]1[cH:5][c:6]([Cl:7])[cH:8][cH:9][n:10]1>>[CH3:1][CH2:2][CH2:3][c:4]1[cH:5][c:6]([Cl:7])[cH:8][cH:9][n:10]1
CCI.Cc1cc(Cl)ccn1
CCCc1cc(Cl)ccn1
null
null
C1CCOC1
C-C Coupling
Friedel-Crafts alkylation with halide
15973705e8ad8fc52aace4e951dc2397c95f8af8fb2361e425388262f1895099
f5e5e22797736d188bba28deb76a4cee8e4fee4dca04fe24f733d2ee68a23361
c1ccncc1
I-[CH2;D2;+0:1]-[C;D1;H3:2].[CH3;D1;+0:3]-[c:4](:[c:5]):[#7;a:6]:[c:7]>>[C;D1;H3:2]-[CH2;D2;+0:1]-[CH2;D2;+0:3]-[c:4](:[c:5]):[#7;a:6]:[c:7]
60
[{"value": 60.0, "product": "ClC1=CC(=NC=C1)CCC", "details": "PERCENTYIELD", "is_desired": false}]
-60
CELSIUS
0.5
HOUR
A 1.5M solution of LDA in hexane (100 mL, 150 mmol) was cooled to -60° C. in an isopropyl alcohol/dry ice bath. To the stirred LDA solution, under nitrogen, was added, dropwise over a 0.5 hours period, a solution of 17.466 g (137 mmol) of 4-chloro-2-picoline (the product of Step 1 of Example 58) in 80 mL of dry THF. Th...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
null
null
c1ccncc1
HI
C1CCOC1
-60
0.5
CCI.Cc1cc(Cl)ccn1>C1CCOC1>CCCc1cc(Cl)ccn1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-919d466c679b402eab41fc7f145b2864
C[C@H](NC(=O)OC(C)(C)C)C(=O)NC1CCNC1.C[C@H](NC(=O)OC(C)(C)C)C(=O)O.NC1CCN(Cc2ccccc2)C1.O=C1CCC(=O)N1O>>C[C@H](N)C(=O)NC1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)C1
ON1C(CCC1=O)=O.C(=O)(OC(C)(C)C)N[C@@H](C)C(=O)NC1CNCC1.NC1CN(CC1)CC1=CC=CC=C1.C(C)(C)(C)OC(=O)N[C@@H](C)C(=O)O>>N[C@@H](C)C(=O)NC1CN(CC1)C=1C=CN2C(C(=CC=C2C1)C(=O)O)=O
CC(C)(C)OC(=O)[NH:3][C@@H:2]([CH3:1])[C:4](=[O:5])[NH:6][CH:7]1[CH2:8][CH2:9][NH:10][CH2:25]1.C[C@H](NC(=O)OC(C)(C)C)[C:18](=[O:19])[OH:20].N[CH:11]1[CH2:12][CH2:13]N(C[c:23]2ccccc2)[CH2:24]1.O=[C:22]1[N:14](O)[C:15](=[O:16])[CH2:17][CH2:21]1>>[CH3:1][C@H:2]([NH2:3])[C:4](=[O:5])[NH:6][CH:7]1[CH2:8][CH2:9][N:10]([c:11]...
C[C@H](NC(=O)OC(C)(C)C)C(=O)NC1CCNC1.C[C@H](NC(=O)OC(C)(C)C)C(=O)O.NC1CCN(Cc2ccccc2)C1.O=C1CCC(=O)N1O
C[C@H](N)C(=O)NC1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)C1
null
null
null
C-C Coupling
OtherReaction
36b19e8a44a944846ed8e7bd03188901c7f52265adcb2d98574ac4841adb71f8
bb3d9244575be890562eeba770fd313c4a09fcf6f990dcd0e29c445795cfa2b1
O=c1cccc2cc(N3CCCC3)ccn12
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C;D1;H3:3])-[C:4](=[O;D1;H0:5])-[#7:6]-[C:7]1-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1.C-[C@H](-N-C(=O)-O-C(-C)(-C)-C)-[C;H0;D3;+0:12](=[O;D1;H0:13])-[O;D1;H1:14].N-[CH;D3;+0:15]1-[CH2;D2;+0:16]-[CH2;D2;+0:17]-N(-C-[c;H0;D3;+0:18]2:c:c:c:c:c:2)-[CH2;D2;+0:19]-1.O-[N;H0;D3;+0:20]1-[C;H...
null
[]
null
null
null
null
3-Amino-1-benzylpyrrolidine (I. Sumio and T. Matsuo, Japanese Kokai JP 5328161, published Mar. 16, 1978) is coupled to N-t-butoxycarbonyl alanine (Boc-Ala) using conventional N-hydroxysuccinimide coupling procedures. The 1-benzyl group is removed by hydrogenolysis in methanol using palladium on carbon catalyst. The 3-(...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Carbamic ester.Carboxylic acid.Ether.Ether.Tertiary amide.Tertiary amide.Primary amine.Secondary amine.Tertiary amine.Boc.Boc
Carboxylic acid.Primary amine.Tertiary amine
C1CCNC1.C1CCNC1.c1ccccc1.C1CC[NH]C1
C1CC[NH]C1.c1cn2ccccc2cc1
C1CC[NH]C1.c1cn2ccccc2cc1
HO-
null
null
null
C[C@H](NC(=O)OC(C)(C)C)C(=O)NC1CCNC1.C[C@H](NC(=O)OC(C)(C)C)C(=O)O.NC1CCN(Cc2ccccc2)C1.O=C1CCC(=O)N1O>>C[C@H](N)C(=O)NC1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)C1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-dbb3e314646f42c4828e49ee8c678c63
CC1CNCCN1.CCOC(=O)c1cc(CC)c2cc(Cl)ccn2c1=O>>CCOC(=O)c1cc(CC)c2cc(N3CCNC(C)C3)ccn2c1=O
ClC=1C=CN2C(C(=CC(=C2C1)CC)C(=O)OCC)=O.CC1NCCNC1>>C(C)C=1C=C(C(N2C=CC(=CC12)N1CC(NCC1)C)=O)C(=O)OCC
[NH:14]1[CH2:15][CH2:16][NH:17][CH:18]([CH3:19])[CH2:20]1.Cl[c:13]1[cH:12][c:11]2[c:8]([CH2:9][CH3:10])[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:24](=[O:25])[n:23]2[cH:22][cH:21]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([CH2:9][CH3:10])[c:11]2[cH:12][c:13]([N:14]3[CH2:15][CH2:16][NH:17][CH:18]([CH3:19]...
CC1CNCCN1.CCOC(=O)c1cc(CC)c2cc(Cl)ccn2c1=O
CCOC(=O)c1cc(CC)c2cc(N3CCNC(C)C3)ccn2c1=O
null
null
N1=CC=CC=C1
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
666b4849793ff533c8edd054666569c3e8ecb55f1bf04ec78a4aed522f7676e2
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=c1cccc2cc(N3CCNCC3)ccn12
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3](:[c:4]):[#7;a:5](:[c:6]):[c:7]:[c:8]:1.[#7:9]1-[C:10]-[C:11]-[NH;D2;+0:12]-[C:13]-[C:14]-1>>[c:6]:[#7;a:5]1:[c:7]:[c:8]:[c;H0;D3;+0:1](-[N;H0;D3;+0:12]2-[C:11]-[C:10]-[#7:9]-[C:14]-[C:13]-2):[c:2]:[c:3]:1:[c:4]
100.5
[{"value": 100.5, "product": "C(C)C=1C=C(C(N2C=CC(=CC12)N1CC(NCC1)C)=O)C(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
65
CELSIUS
null
null
Ethyl 8-chloro-1-ethyl-4H-quinolizin-4-one-3-carboxylate (558 mg, 2.0 mmol), the product of Step 3 of Example 62, was dissolved in 10 mL of dry pyridine under a nitrogen atmosphere. To the resultant solution was added 600 mg (6.0 mmol) of 2-methylpiperazine and the stirred reaction mixture was heated at 65° C. for 3 ho...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
C1CNCCN1.c1cn2ccccc2cc1
c1cn2ccccc2cc1.C1C[NH]CCN1
c1cn2ccccc2cc1.C1C[NH]CCN1
HCl
N1=CC=CC=C1
65
null
CC1CNCCN1.CCOC(=O)c1cc(CC)c2cc(Cl)ccn2c1=O>N1=CC=CC=C1>CCOC(=O)c1cc(CC)c2cc(N3CCNC(C)C3)ccn2c1=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-9473a5b4f44b4bc8b8cc65bad100e385
CCOC(=O)c1cc(CC)c2cc(N3CCNC(C)C3)ccn2c1=O>>CCc1cc(C(=O)O)c(=O)n2ccc(N3CCNC(C)C3)cc12
[OH-].[Na+].C(C)C=1C=C(C(N2C=CC(=CC12)N1CC(NCC1)C)=O)C(=O)OCC.Cl>>Cl.C(C)C=1C=C(C(N2C=CC(=CC12)N1CC(NCC1)C)=O)C(=O)O
CC[O:8][C:6]([c:5]1[cH:4][c:3]([CH2:2][CH3:1])[c:23]2[n:11]([c:9]1=[O:10])[cH:12][cH:13][c:14]([N:15]1[CH2:16][CH2:17][NH:18][CH:19]([CH3:20])[CH2:21]1)[cH:22]2)=[O:7]>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]([C:6](=[O:7])[OH:8])[c:9](=[O:10])[n:11]2[cH:12][cH:13][c:14]([N:15]3[CH2:16][CH2:17][NH:18][CH:19]([CH3:20])[CH2:21]3)...
CCOC(=O)c1cc(CC)c2cc(N3CCNC(C)C3)ccn2c1=O
CCc1cc(C(=O)O)c(=O)n2ccc(N3CCNC(C)C3)cc12
null
null
C1CCOC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=c1cccc2cc(N3CCNCC3)ccn12
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
55
[{"value": 55.0, "product": "Cl.C(C)C=1C=C(C(N2C=CC(=CC12)N1CC(NCC1)C)=O)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}]
65
CELSIUS
3
HOUR
To a suspension of 0.686 g (2 mmol) of ethyl 1-ethyl-8-(3-methyl-1-piperazinyl)-4H-quinolizin-4-one-3-carboxylate, from Step 1, in 8 mL of THF was added 8.0 mL of a 1.0N aqueous sodium hydroxide solution and the reaction mixture was heated, with stirring, at 65° C. for 3 hours. The THF was removed from the reaction mix...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cn2ccccc2cc1.C1C[NH]CCN1
Other
C1CCOC1
65
3
CCOC(=O)c1cc(CC)c2cc(N3CCNC(C)C3)ccn2c1=O>C1CCOC1>CCc1cc(C(=O)O)c(=O)n2ccc(N3CCNC(C)C3)cc12
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-ba268a942a684f5bae96f7015e014325
CCOC(=O)c1cc(CC)c2cc(Cl)ccn2c1=O.CN1CCNCC1>>CCOC(=O)c1cc(CC)c2cc(N3CCN(C)CC3)ccn2c1=O
ClC=1C=CN2C(C(=CC(=C2C1)CC)C(=O)OCC)=O.CN1CCNCC1>>C(C)C=1C=C(C(N2C=CC(=CC12)N1CCN(CC1)C)=O)C(=O)OCC
Cl[c:13]1[cH:12][c:11]2[c:8]([CH2:9][CH3:10])[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:24](=[O:25])[n:23]2[cH:22][cH:21]1.[NH:14]1[CH2:15][CH2:16][N:17]([CH3:18])[CH2:19][CH2:20]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([CH2:9][CH3:10])[c:11]2[cH:12][c:13]([N:14]3[CH2:15][CH2:16][N:17]([CH3:18])[CH2:19...
CCOC(=O)c1cc(CC)c2cc(Cl)ccn2c1=O.CN1CCNCC1
CCOC(=O)c1cc(CC)c2cc(N3CCN(C)CC3)ccn2c1=O
null
null
N1=CC=CC=C1
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
d1eef4f8c0aa68dde2b04e6a19bf2997a325e5677cab2bf9db6ffa7b61f605c2
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=c1cccc2cc(N3CCNCC3)ccn12
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3](:[c:4]):[#7;a:5](:[c:6]):[c:7]:[c:8]:1.[#7:9]1-[C:10]-[C:11]-[NH;D2;+0:12]-[C:13]-[C:14]-1>>[c:6]:[#7;a:5]1:[c:7]:[c:8]:[c;H0;D3;+0:1](-[N;H0;D3;+0:12]2-[C:11]-[C:10]-[#7:9]-[C:14]-[C:13]-2):[c:2]:[c:3]:1:[c:4]
99.9
[{"value": 99.9, "product": "C(C)C=1C=C(C(N2C=CC(=CC12)N1CCN(CC1)C)=O)C(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
85
CELSIUS
null
null
Ethyl 8-chloro-1-ethyl-4H-quinolizin-4-one-3-carboxylate (279 mg, 1.0 mmol), the product of Step 3 of Example 62, was dissolved in 5 mL of dry pyridine under a nitrogen atmosphere. To the resultant solution was added 2 mL (2.0 mmol) of N-methylpiperazine and the stirred reaction mixture was heated at 85° C. for 2.5 hou...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
c1cn2ccccc2cc1.C1CNCC[NH]1
c1cn2ccccc2cc1.C1C[NH]CC[NH]1
c1cn2ccccc2cc1.C1C[NH]CC[NH]1
HCl
N1=CC=CC=C1
85
null
CCOC(=O)c1cc(CC)c2cc(Cl)ccn2c1=O.CN1CCNCC1>N1=CC=CC=C1>CCOC(=O)c1cc(CC)c2cc(N3CCN(C)CC3)ccn2c1=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-4f8eca8686f04fab850d92ff0dd05c7a
CCOC(=O)c1cc(CC)c2cc(N3CCN(C)CC3)ccn2c1=O>>CCc1cc(C(=O)O)c(=O)n2ccc(N3CCN(C)CC3)cc12
Cl.C(C)C=1C=C(C(N2C=CC(=CC12)N1CCN(CC1)C)=O)C(=O)OCC.[OH-].[Na+]>>Cl.C(C)C=1C=C(C(N2C=CC(=CC12)N1CCN(CC1)C)=O)C(=O)O
CC[O:8][C:6]([c:5]1[cH:4][c:3]([CH2:2][CH3:1])[c:23]2[n:11]([c:9]1=[O:10])[cH:12][cH:13][c:14]([N:15]1[CH2:16][CH2:17][N:18]([CH3:19])[CH2:20][CH2:21]1)[cH:22]2)=[O:7]>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]([C:6](=[O:7])[OH:8])[c:9](=[O:10])[n:11]2[cH:12][cH:13][c:14]([N:15]3[CH2:16][CH2:17][N:18]([CH3:19])[CH2:20][CH2:21]3)...
CCOC(=O)c1cc(CC)c2cc(N3CCN(C)CC3)ccn2c1=O
CCc1cc(C(=O)O)c(=O)n2ccc(N3CCN(C)CC3)cc12
null
null
C1CCOC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=c1cccc2cc(N3CCNCC3)ccn12
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
68
[{"value": 68.0, "product": "Cl.C(C)C=1C=C(C(N2C=CC(=CC12)N1CCN(CC1)C)=O)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}]
75
CELSIUS
4.5
HOUR
To a solution of 171 mg (0.5 mmol) of ethyl 1-ethyl-8-(4-methylpiperazin-1-yl)-4H-quinolizin-4-one-3-carboxylate, from Step 1, in 4 mL of THF was added 4.0 mL of a 1.0N aqueous sodium hydroxide solution and the reaction mixture was heated, with stirring, at 75° C. for 4.5 hours. The reaction mixture was cooled to ambie...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1cn2ccccc2cc1.C1C[NH]CC[NH]1
Other
C1CCOC1
75
4.5
CCOC(=O)c1cc(CC)c2cc(N3CCN(C)CC3)ccn2c1=O>C1CCOC1>CCc1cc(C(=O)O)c(=O)n2ccc(N3CCN(C)CC3)cc12
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-784765bd050b4df79dbabcefd7283ef9
O=C([O-])CC(CC(=O)[O-])c1ccc([N+](=O)[O-])cn1>>Cc1ccc([N+](=O)[O-])cn1
[OH-].[Na+].[N+](=O)([O-])C=1C=CC(=NC1)C(CC(=O)[O-])CC(=O)[O-]>>[N+](=O)([O-])C=1C=CC(=NC1)C
O=C([O-])C[CH:1](CC(=O)[O-])[c:2]1[cH:3][cH:4][c:5]([N+:6](=[O:7])[O-:8])[cH:9][n:10]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([N+:6](=[O:7])[O-:8])[cH:9][n:10]1
O=C([O-])CC(CC(=O)[O-])c1ccc([N+](=O)[O-])cn1
Cc1ccc([N+](=O)[O-])cn1
null
null
S(O)(O)(=O)=O
Reduction
OtherReaction
0bc3968b35f0839c230afb4215314da278abd4e1f10e42ec3012c5512de49ea5
312e9350dcad67590617294c0eb017edf0b9fbfe6133c06a3f393b871a889092
c1ccncc1
O=C(-[O-])-C-[CH;D3;+0:1](-C-C(=O)-[O-])-[c:2](:[c:3]):[#7;a:4]:[c:5]>>[CH3;D1;+0:1]-[c:2](:[c:3]):[#7;a:4]:[c:5]
92
[{"value": 92.0, "product": "[N+](=O)([O-])C=1C=CC(=NC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.0, "product": "[N+](=O)([O-])C=1C=CC(=NC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A suspension of 102.0 g (0.361 mol) of 2-(5-nitro-2-pyridyl)-1,3-propanedicarboxylate, from Step 1, in 600 mL of 20% aqueous sulfuric acid solution was heated at 95° C. for 24 hours. The resultant solution was poured onto 1 kg of ice and the aqueous mixture was adjusted to a pH within the range pH 10-12 with 50% aqueou...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccncc1
HO-
S(O)(O)(=O)=O
null
null
O=C([O-])CC(CC(=O)[O-])c1ccc([N+](=O)[O-])cn1>S(O)(O)(=O)=O>Cc1ccc([N+](=O)[O-])cn1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-c5f292609ba64fafa75e76f067d6b75e
Cc1ccc(F)cn1.OO>>Cc1ccc(F)c[n+]1[O-]
FC=1C=CC(=NC1)C.C(C)(=O)OO.OO.C([O-])([O-])=O.[K+].[K+]>>FC1=CC=C([N+](=C1)[O-])C
[CH3:1][c:2]1[cH:3][cH:4][c:5]([F:6])[cH:7][n:8]1.O[OH:9]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([F:6])[cH:7][n+:8]1[O-:9]
Cc1ccc(F)cn1.OO
Cc1ccc(F)c[n+]1[O-]
null
null
C(C)(=O)O
Functional Group Interconversion
OtherReaction
d7f3c84fb751fef5567bc0e84a2e7c0afb271257e8dfb17aa871e038ff1a84c7
bf536f3bf8ed7b8faf08cf1c004ccd0a5e7fe59339402dd73ac837bb4a52f2ba
c1cc[nH+]cc1
O-[OH;D1;+0:1].[C;D1;H3:2]-[c:3](:[c:4]):[n;H0;D2;+0:5]:[c:6]:[c:7]>>[C;D1;H3:2]-[c:3](:[c:4]):[n+;H0;D3:5](-[O-;H0;D1:1]):[c:6]:[c:7]
22
[{"value": 22.0, "product": "FC1=CC=C([N+](=C1)[O-])C", "details": "PERCENTYIELD", "is_desired": false}]
50
CELSIUS
4
HOUR
To the solution of 5-fluoro-2-picoline obtained in Step 4, at 0° C., was added, with vigorous stirring, a cold solution of 40% peracetic acid (prepared by carefully adding 50 mL of 30% hydrogen peroxide solution to 150 mL of glacial acetic acid). The reaction mixture was heated at reflux temperature (50° C.) for 4 days...
10.6084/m9.figshare.5104873.v1
null
Peroxide
null
c1ccncc1
C1=CC=[NH+]C=C1
C1=CC=[NH+]C=C1
HO-
C(C)(=O)O
50
4
Cc1ccc(F)cn1.OO>C(C)(=O)O>Cc1ccc(F)c[n+]1[O-]
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-2f9949b0e5874a0b8b55bdaaeb8c3283
Cc1ccc(F)c[n+]1[O-]>>Cc1cc([N+](=O)[O-])c(F)c[n+]1[O-]
S(O)(O)(=O)=O.[N+](=O)([O-])[O-].[K+].C([O-])([O-])=O.[K+].[K+].[OH-].[Na+].FC1=CC=C([N+](=C1)[O-])C.FC1=CC=C([N+](=C1)[O-])C.[N+](=O)([O-])[O-].[K+]>>FC1=C(C=C([N+](=C1)[O-])C)[N+](=O)[O-]
[CH3:1][c:2]1[cH:3][cH:4][c:8]([F:9])[cH:10][n+:11]1[O-:12]>>[CH3:1][c:2]1[cH:3][c:4]([N+:5](=[O:6])[O-:7])[c:8]([F:9])[cH:10][n+:11]1[O-:12]
Cc1ccc(F)c[n+]1[O-]
Cc1cc([N+](=O)[O-])c(F)c[n+]1[O-]
null
null
null
Functional Group Addition
OtherReaction
d1758a3dd09d130b0b6f98cf4f20aa520271dd0a99b430b7cead3eb29332a65b
22f3183026a2d99c91ec0c53f0059a15c8421016bd62c8ab45281362b96dc686
c1cc[nH+]cc1
[C;D1;H3:1]-[c:2]1:[c:3]:[cH;D2;+0:4]:[c:5](-[F;D1;H0:6]):[c:7]:[#7;a;+:8]:1-[O;-;D1;H0:9]>>[C;D1;H3:1]-[c:2]1:[c:3]:[c;H0;D3;+0:4](-[#7;+:10](-[O;-;D1;H0:11])=[O;D1;H0:12]):[c:5](-[F;D1;H0:6]):[c:7]:[#7;a;+:8]:1-[O;-;D1;H0:9]
80
[{"value": 80.0, "product": "FC1=C(C=C([N+](=C1)[O-])C)[N+](=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}]
50
CELSIUS
18
HOUR
The reaction was carried out in a flask vented to a gas scrubber containing aqueous sodium hydroxide solution. The product of Step 5, 5-fluoro-2-picoline-N-oxide (1.0 g, 7.86 mmol) was cooled to 0° C. and concentrated sulfuric acid (4.2 mL) was slowly added, with stirring. Solid potassium nitrate (1.27 g, 12.5 mmol) wa...
10.6084/m9.figshare.5104873.v1
null
null
Nitro group
C1=CC=[NH+]C=C1
C1=CC=[NH+]C=C1
C1=CC=[NH+]C=C1
Other
null
50
18
Cc1ccc(F)c[n+]1[O-]>>Cc1cc([N+](=O)[O-])c(F)c[n+]1[O-]
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-9c15659462ee47fb96bbf189ac58fe27
Cc1cc(Cl)c(F)c[n+]1[O-]>>Cc1cc(Cl)c(F)cn1
ClC=1C=C([N+](=CC1F)[O-])C.C([O-])([O-])=O.[K+].[K+]>>ClC1=CC(=NC=C1F)C
[O-][n+:9]1[c:2]([CH3:1])[cH:3][c:4]([Cl:5])[c:6]([F:7])[cH:8]1>>[CH3:1][c:2]1[cH:3][c:4]([Cl:5])[c:6]([F:7])[cH:8][n:9]1
Cc1cc(Cl)c(F)c[n+]1[O-]
Cc1cc(Cl)c(F)cn1
null
[Fe]
C(C)(=O)O
Functional Group Interconversion
OtherReaction
8660dc08f9c4d3b8c6814ee1b12714454b2bd6ddbe4d55cbaaeb274a83637cea
f1bbf9aa3c82f5e49be9f6d53533b6bb152f359232b6d32090c168949766aa71
c1ccncc1
[C;D1;H3:1]-[c:2](:[c:3]):[n+;H0;D3:4](-[O-]):[c:5]:[c:6]>>[C;D1;H3:1]-[c:2](:[c:3]):[n;H0;D2;+0:4]:[c:5]:[c:6]
142.1
[{"value": 71.0, "product": "ClC1=CC(=NC=C1F)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 142.1, "product": "ClC1=CC(=NC=C1F)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
4-Chloro-5-fluoro-2-picoline-N-oxide (12.43 g, 76.93 mmol), from Step 7, was dissolved in 52 mL of glacial acetic acid in a 3-necked flask equiped with a mechanical stirrer, a condenser and a thermometer. Iron powder (6.45 g, 115.5 mmol) was added to the solution at ambient temperature and the reaction mixture was care...
10.6084/m9.figshare.5104873.v1
null
null
null
C1=CC=[NH+]C=C1
c1ccncc1
c1ccncc1
Other
[Fe].C(C)(=O)O
null
0.166667
Cc1cc(Cl)c(F)c[n+]1[O-]>[Fe].C(C)(=O)O>Cc1cc(Cl)c(F)cn1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-1ecb12c0a720485081b2a903dedaad68
CC(C)(C)OCl.Cc1cc(Cl)c(F)cn1>>Cc1ncc(F)c(Cl)c1Cl
O.ClC1=CC(=NC=C1F)C.ClC1=CC(=NC=C1F)C.C(C)(C)(C)OCl>>ClC=1C(=NC=C(C1Cl)F)C
CC(C)(C)O[Cl:10].[CH3:1][c:2]1[n:3][cH:4][c:5]([F:6])[c:7]([Cl:8])[cH:9]1>>[CH3:1][c:2]1[n:3][cH:4][c:5]([F:6])[c:7]([Cl:8])[c:9]1[Cl:10]
CC(C)(C)OCl.Cc1cc(Cl)c(F)cn1
Cc1ncc(F)c(Cl)c1Cl
null
null
C(Cl)(Cl)Cl
Functional Group Interconversion
Chlorination
66a492ff31bfcbb52d9a760416ba269a4cf5a439a6c2ca9c2c3a3ed0a750b974
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccncc1
C-C(-C)(-C)-O-[Cl;H0;D1;+0:1].[C;D1;H3:2]-[c:3]1:[#7;a:4]:[c:5]:[c:6]:[c:7](-[Cl;D1;H0:8]):[cH;D2;+0:9]:1>>[C;D1;H3:2]-[c:3]1:[#7;a:4]:[c:5]:[c:6]:[c:7](-[Cl;D1;H0:8]):[c;H0;D3;+0:9]:1-[Cl;H0;D1;+0:1]
null
[]
0
CELSIUS
2
HOUR
To 0.87 g (6 mmol) of 4-chloro-5-fluoro-2-picoline, the product of Example 66, in 20 mL of chloroform cooled to -45° C., is added 0.75 mL of t-butylhypochlorite. The reaction mixture is stirred at -45° C. for 2 hours and at 0° C. for 2 hours. The reaction mixture is then poured into water and the resultant aqueous mixt...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccncc1
c1ccncc1
c1ccncc1
HO-
C(Cl)(Cl)Cl
0
2
CC(C)(C)OCl.Cc1cc(Cl)c(F)cn1>C(Cl)(Cl)Cl>Cc1ncc(F)c(Cl)c1Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-a549bdf2b11747b18714efb6d4d43a8c
BrBr.Cc1cc(Cl)c(F)cn1>>Cc1ncc(F)c(Cl)c1Br
S(O)(O)(=O)=O.ClC1=CC(=NC=C1F)C.ClC1=CC(=NC=C1F)C.BrBr>>BrC=1C(=NC=C(C1Cl)F)C
Br[Br:10].[CH3:1][c:2]1[n:3][cH:4][c:5]([F:6])[c:7]([Cl:8])[cH:9]1>>[CH3:1][c:2]1[n:3][cH:4][c:5]([F:6])[c:7]([Cl:8])[c:9]1[Br:10]
BrBr.Cc1cc(Cl)c(F)cn1
Cc1ncc(F)c(Cl)c1Br
null
null
null
Functional Group Interconversion
Bromination
66a492ff31bfcbb52d9a760416ba269a4cf5a439a6c2ca9c2c3a3ed0a750b974
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccncc1
Br-[Br;H0;D1;+0:1].[C;D1;H3:2]-[c:3]1:[#7;a:4]:[c:5]:[c:6]:[c:7](-[Cl;D1;H0:8]):[cH;D2;+0:9]:1>>[Br;H0;D1;+0:1]-[c;H0;D3;+0:9]1:[c:3](-[C;D1;H3:2]):[#7;a:4]:[c:5]:[c:6]:[c:7]:1-[Cl;D1;H0:8]
null
[]
null
null
null
null
4-Chloro-5-fluoro-2-picoline, the product of Example 66, is treated with bromine in fuming sulfuric acid containing 65% sulfur trioxide for 7 hours at 80° C. as described by L. van der Does and H. J. Hertog in Rec Trav Chim 81: 864 (1965) to afford the title compound. Conditions: See reaction.notes.procedure_details. W...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccncc1
c1ccncc1
c1ccncc1
HBr
null
null
null
BrBr.Cc1cc(Cl)c(F)cn1>>Cc1ncc(F)c(Cl)c1Br
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-6be519bfa24b404b82af4b0e9d174bb5
CC(=O)OF.Cc1cc(Cl)c(F)cn1>>Cc1ncc(F)c(Cl)c1F
ClC1=CC(=NC=C1F)C.FOC(C)=O>>ClC1=C(C(=NC=C1F)C)F
CC(=O)O[F:10].[CH3:1][c:2]1[n:3][cH:4][c:5]([F:6])[c:7]([Cl:8])[cH:9]1>>[CH3:1][c:2]1[n:3][cH:4][c:5]([F:6])[c:7]([Cl:8])[c:9]1[F:10]
CC(=O)OF.Cc1cc(Cl)c(F)cn1
Cc1ncc(F)c(Cl)c1F
null
null
null
Functional Group Interconversion
OtherReaction
66a492ff31bfcbb52d9a760416ba269a4cf5a439a6c2ca9c2c3a3ed0a750b974
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccncc1
C-C(=O)-O-[F;H0;D1;+0:1].[C;D1;H3:2]-[c:3]1:[#7;a:4]:[c:5]:[c:6]:[c:7](-[Cl;D1;H0:8]):[cH;D2;+0:9]:1>>[C;D1;H3:2]-[c:3]1:[#7;a:4]:[c:5]:[c:6]:[c:7](-[Cl;D1;H0:8]):[c;H0;D3;+0:9]:1-[F;H0;D1;+0:1]
null
[]
null
null
null
null
4-Chloro-5-fluoro-2-picoline is treated with 1.1 equivalents of acetyl hypofluorite as described by O. Lerman, et al. J Org Chem, 49: 806-813 (1984) to afford the title compound. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccncc1
c1ccncc1
c1ccncc1
HO-
null
null
null
CC(=O)OF.Cc1cc(Cl)c(F)cn1>>Cc1ncc(F)c(Cl)c1F
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-40d48fdd456840b9bb764160e1bbdceb
CCI.Cc1cc(Cl)c(F)cn1>>CCCc1cc(Cl)c(F)cn1
C(C)I.C(CCC)[Li].ClC1=CC(=NC=C1F)C.C(C)(C)NC(C)C.C(C)(C)[N-]C(C)C.[Li+].C(C)(C)[N-]C(C)C.[Li+]>>ClC1=CC(=NC=C1F)CCC
I[CH2:2][CH3:1].[CH3:3][c:4]1[cH:5][c:6]([Cl:7])[c:8]([F:9])[cH:10][n:11]1>>[CH3:1][CH2:2][CH2:3][c:4]1[cH:5][c:6]([Cl:7])[c:8]([F:9])[cH:10][n:11]1
CCI.Cc1cc(Cl)c(F)cn1
CCCc1cc(Cl)c(F)cn1
null
null
C1CCOC1
C-C Coupling
Friedel-Crafts alkylation with halide
15973705e8ad8fc52aace4e951dc2397c95f8af8fb2361e425388262f1895099
f5e5e22797736d188bba28deb76a4cee8e4fee4dca04fe24f733d2ee68a23361
c1ccncc1
I-[CH2;D2;+0:1]-[C;D1;H3:2].[CH3;D1;+0:3]-[c:4](:[c:5]):[#7;a:6]:[c:7]>>[C;D1;H3:2]-[CH2;D2;+0:1]-[CH2;D2;+0:3]-[c:4](:[c:5]):[#7;a:6]:[c:7]
null
[]
-78
CELSIUS
5
HOUR
Diisopropylamine (924 μL, 6.59 mmol) was dissolved in 9 mL of dry THF and the resultant solution was cooled to 0° C. in an ice bath. n-Butyllithium (3.07 mL of a 2.05M solution in THF, 6.29 mmol) was added via syringe to the amine solution and the resultant solution was stirred for 30 minutes at 0° C. The lithium diiso...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
null
null
c1ccncc1
HI
C1CCOC1
-78
5
CCI.Cc1cc(Cl)c(F)cn1>C1CCOC1>CCCc1cc(Cl)c(F)cn1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-35690c6e645f4d1f972faf4b4a3c07c5
CCCc1cc(Cl)c(F)cn1>>CCCc1ncc(F)c(Cl)c1Cl
ClC1=CC(=NC=C1F)CCC.ClC1=CC(=NC=C1F)C.ClC1=CC(=NC=C1F)C.ClC1=CC(=NC=C1F)CCC>>ClC=1C(=NC=C(C1Cl)F)CCC
[CH3:1][CH2:2][CH2:3][c:4]1[n:5][cH:6][c:7]([F:8])[c:9]([Cl:10])[cH:11]1>>[CH3:1][CH2:2][CH2:3][c:4]1[n:5][cH:6][c:7]([F:8])[c:9]([Cl:10])[c:11]1[Cl:12]
CCCc1cc(Cl)c(F)cn1
CCCc1ncc(F)c(Cl)c1Cl
null
null
null
Functional Group Addition
Aromatic chlorination
7c108e53aa6849672ac0ea1998cfd24df7835b0d1bc5738d16f4d561a472c88e
0a2f22058f27970cef4a98a778644dbe9c44e91f66c74cd24db321993177608a
c1ccncc1
[C:1]-[c:2]1:[#7;a:3]:[c:4]:[c:5]:[c:6](-[Cl;D1;H0:7]):[cH;D2;+0:8]:1>>[C:1]-[c:2]1:[#7;a:3]:[c:4]:[c:5]:[c:6](-[Cl;D1;H0:7]):[c;H0;D3;+0:8]:1-[Cl;D1;H0:9]
null
[]
null
null
null
null
By following the procedures described in Example 67 and replacing 4-chloro-5-fluoro-2-picoline (the product of Example 66) with 4-chloro-5-fluoro-2-propyl-pyridine (the product of Example 70), the title compound can be prepared. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccncc1
c1ccncc1
c1ccncc1
Other
null
null
null
CCCc1cc(Cl)c(F)cn1>>CCCc1ncc(F)c(Cl)c1Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-cf330283adb847978dd3b58700a37b8c
CCCc1cc(Cl)c(F)cn1>>CCCc1ncc(F)c(Cl)c1F
ClC1=CC(=NC=C1F)CCC.ClC1=CC(=NC=C1F)C.ClC1=CC(=NC=C1F)C.ClC1=CC(=NC=C1F)CCC>>ClC1=C(C(=NC=C1F)CCC)F
[CH3:1][CH2:2][CH2:3][c:4]1[n:5][cH:6][c:7]([F:8])[c:9]([Cl:10])[cH:11]1>>[CH3:1][CH2:2][CH2:3][c:4]1[n:5][cH:6][c:7]([F:8])[c:9]([Cl:10])[c:11]1[F:12]
CCCc1cc(Cl)c(F)cn1
CCCc1ncc(F)c(Cl)c1F
null
null
null
Functional Group Addition
Aromatic fluorination
7c108e53aa6849672ac0ea1998cfd24df7835b0d1bc5738d16f4d561a472c88e
0a2f22058f27970cef4a98a778644dbe9c44e91f66c74cd24db321993177608a
c1ccncc1
[C:1]-[c:2]1:[#7;a:3]:[c:4]:[c:5]:[c:6](-[Cl;D1;H0:7]):[cH;D2;+0:8]:1>>[C:1]-[c:2]1:[#7;a:3]:[c:4]:[c:5]:[c:6](-[Cl;D1;H0:7]):[c;H0;D3;+0:8]:1-[F;D1;H0:9]
null
[]
null
null
null
null
By following the procedures described in Example 69 and replacing 4-chloro-5-fluoro-2-picoline (the product of Example 66) with 4-chloro-5-fluoro-2-propyl-pyridine (the product of Example 70), the title compound can be prepared. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccncc1
c1ccncc1
c1ccncc1
Other
null
null
null
CCCc1cc(Cl)c(F)cn1>>CCCc1ncc(F)c(Cl)c1F
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-b9b54b14eaa34567839b3bc713494b14
Cc1cc(Cl)c(F)cn1.O=C1CCC(=O)N1Br>>CC1(Br)C=C(Cl)C(F)=CN1
CC(C)(C#N)N=NC(C)(C)C#N.ClC1=CC(=NC=C1F)C.ClC1=CC(=NC=C1F)C.BrN1C(CCC1=O)=O>>ClC1=CC(NC=C1F)(C)Br
[CH3:1][c:2]1[cH:4][c:5]([Cl:6])[c:7]([F:8])[cH:9][n:10]1.O=C1CCC(=O)N1[Br:3]>>[CH3:1][C:2]1([Br:3])[CH:4]=[C:5]([Cl:6])[C:7]([F:8])=[CH:9][NH:10]1
Cc1cc(Cl)c(F)cn1.O=C1CCC(=O)N1Br
CC1(Br)C=C(Cl)C(F)=CN1
null
null
C(Cl)Cl.ClCCCl
Functional Group Interconversion
OtherReaction
a5011706c3b542cad82b76bbbf2532a9330903bdef3a651fec89f9efae3345a4
d68a01110e168c02e5a14d46a91c97d2353cca8f6d85d864624a3298918472b0
C1=CCNC=C1
O=C1-C-C-C(=O)-N-1-[Br;H0;D1;+0:1].[C;D1;H3:2]-[c;H0;D3;+0:3]1:[cH;D2;+0:4]:[c;H0;D3;+0:5](-[Cl;D1;H0:6]):[c;H0;D3;+0:7](-[F;D1;H0:8]):[cH;D2;+0:9]:[n;H0;D2;+0:10]:1>>[Br;H0;D1;+0:1]-[C;H0;D4;+0:3]1(-[C;D1;H3:2])-[CH;D2;+0:4]=[C;H0;D3;+0:5](-[Cl;D1;H0:6])-[C;H0;D3;+0:7](-[F;D1;H0:8])=[CH;D2;+0:9]-[NH;D2;+0:10]-1
69
[{"value": 69.0, "product": "ClC1=CC(NC=C1F)(C)Br", "details": "PERCENTYIELD", "is_desired": false}]
75
CELSIUS
null
null
4-Chloro-5-fluoro-2-picoline (2.9 g, 20 mmol), the product of Example 66, was dissolved in 50 mL of 1,2-dichloroethane in a dry flask. The resultant solution was heated, with stirring, to 75° C. and 4.09 (23 mmol) of N-bromosuccinimide was added, followed by 100 mG (0.7 mmol) of 2,2-azobisisobutyronirile (AIBN), a free...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Tertiary amide.Tertiary amide
Enamine.Tertiary halide.Alkenyl halide.Alkenyl halide
c1ccncc1.C1CCNC1
C1=CCNC=C1
C1=CCNC=C1
HO-
C(Cl)Cl.ClCCCl
75
null
Cc1cc(Cl)c(F)cn1.O=C1CCC(=O)N1Br>C(Cl)Cl.ClCCCl>CC1(Br)C=C(Cl)C(F)=CN1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-a310f335f3e844efadd43206c4a310e4
CC1(Br)C=C(Cl)C(F)=CN1.CN>>CNCc1cc(Cl)c(F)cn1
ClC1=CC(NC=C1F)(C)Br.CN>>ClC1=CC(=NC=C1F)CNC
Br[C:4]1([CH3:3])[CH:5]=[C:6]([Cl:7])[C:8]([F:9])=[CH:10][NH:11]1.[CH3:1][NH2:2]>>[CH3:1][NH:2][CH2:3][c:4]1[cH:5][c:6]([Cl:7])[c:8]([F:9])[cH:10][n:11]1
CC1(Br)C=C(Cl)C(F)=CN1.CN
CNCc1cc(Cl)c(F)cn1
null
null
CO
Aromatic Heterocycle Formation
OtherReaction
89c5e51da84b17b94a10ac0183ba706b07e9fdcd804405a5bd1f7d8228653361
b2680e4f3eb35cf11f81268e8fcd711678a40fd9bd43a0fd5cc2b47a013eabce
c1ccncc1
Br-[C;H0;D4;+0:1]1(-[CH3;D1;+0:2])-[CH;D2;+0:3]=[C;H0;D3;+0:4](-[Cl;D1;H0:5])-[C;H0;D3;+0:6](-[F;D1;H0:7])=[CH;D2;+0:8]-[NH;D2;+0:9]-1.[C;D1;H3:10]-[NH2;D1;+0:11]>>[C;D1;H3:10]-[NH;D2;+0:11]-[CH2;D2;+0:2]-[c;H0;D3;+0:1]1:[cH;D2;+0:3]:[c;H0;D3;+0:4](-[Cl;D1;H0:5]):[c;H0;D3;+0:6](-[F;D1;H0:7]):[cH;D2;+0:8]:[n;H0;D2;+0:9]...
70
[{"value": 70.0, "product": "ClC1=CC(=NC=C1F)CNC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
26
HOUR
4-Chloro-5-fluoro-alpha-bromo-2-picoline (1.37 g, 6.1 mmol), from Step 1 was dissolved in 15 mL of methanol in a pressure tube. Methylamine (3 mL of 40% aqueous solution) was added to the tube and the tube was sealed. The reaction mixture was stirred at ambient temperature for 26 hours and then the solvent was removed ...
10.6084/m9.figshare.5104873.v1
null
Enamine.Tertiary halide.Alkenyl halide.Alkenyl halide.Primary amine
Aromatic halide.Aromatic halide.Secondary amine
C1=CCNC=C1
c1ccncc1
c1ccncc1
HBr
CO
null
26
CC1(Br)C=C(Cl)C(F)=CN1.CN>CO>CNCc1cc(Cl)c(F)cn1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-7367f512f50b4d5a8670fe6f388da171
CCOC(=O)c1cc(NC)c2cc(Cl)c(F)cn2c1=O.CN1CCNCC1>>CCOC(=O)c1cc(NC)c2cc(N3CCN(C)CC3)c(F)cn2c1=O
ClC=1C(=CN2C(C(=CC(=C2C1)NC)C(=O)OCC)=O)F.ClC=1C(=CN2C(C(=CC(=C2C1)NC)C(=O)OCC)=O)F.CN1CCNCC1>>FC1=CN2C(C(=CC(=C2C=C1N1CCN(CC1)C)NC)C(=O)OCC)=O
Cl[c:13]1[cH:12][c:11]2[c:8]([NH:9][CH3:10])[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:25](=[O:26])[n:24]2[cH:23][c:21]1[F:22].[NH:14]1[CH2:15][CH2:16][N:17]([CH3:18])[CH2:19][CH2:20]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([NH:9][CH3:10])[c:11]2[cH:12][c:13]([N:14]3[CH2:15][CH2:16][N:17]([CH3:18])[CH2...
CCOC(=O)c1cc(NC)c2cc(Cl)c(F)cn2c1=O.CN1CCNCC1
CCOC(=O)c1cc(NC)c2cc(N3CCN(C)CC3)c(F)cn2c1=O
null
null
N1=CC=CC=C1
Heteroatom Alkylation and Arylation
Ullmann-Goldberg Substitution amine
d1eef4f8c0aa68dde2b04e6a19bf2997a325e5677cab2bf9db6ffa7b61f605c2
b6b8e2cdb45054a35f5e8157d624f852c0601a09401556706e166b19536eb7a7
O=c1cccc2cc(N3CCNCC3)ccn12
Cl-[c;H0;D3;+0:1]1:[c:2]:[c:3](:[c:4]):[#7;a:5](:[c:6]):[c:7]:[c:8]:1-[F;D1;H0:9].[#7:10]1-[C:11]-[C:12]-[NH;D2;+0:13]-[C:14]-[C:15]-1>>[F;D1;H0:9]-[c:8]1:[c:7]:[#7;a:5](:[c:6]):[c:3](:[c:4]):[c:2]:[c;H0;D3;+0:1]:1-[N;H0;D3;+0:13]1-[C:12]-[C:11]-[#7:10]-[C:15]-[C:14]-1
null
[]
70
CELSIUS
null
null
Ethyl 8-chloro-7-fluoro-1-methylamino-4H-quinolizin-4-one-3-carboxylate (899 mg, 3.0 mmol), the product of Step 6, is suspended in 12 mL of dry pyridine under a nitrogen atmosphere. To the resultant solution is added 6.0 mL (6.0 mmol) of N-methylpiperazine and the reaction mixture is heated at 70° C. for 8 hours. The r...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Tertiary amine
c1cn2ccccc2cc1.C1CNCC[NH]1
c1cn2ccccc2cc1.C1C[NH]CC[NH]1
c1cn2ccccc2cc1.C1C[NH]CC[NH]1
HCl
N1=CC=CC=C1
70
null
CCOC(=O)c1cc(NC)c2cc(Cl)c(F)cn2c1=O.CN1CCNCC1>N1=CC=CC=C1>CCOC(=O)c1cc(NC)c2cc(N3CCN(C)CC3)c(F)cn2c1=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-abe903ec14e54584b4ff8c0f401a1f41
CCOC(=O)c1cc(NC)c2cc(N3CCN(C)CC3)c(F)cn2c1=O>>CN1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)CC1
Cl.[OH-].[Na+].FC1=CN2C(C(=CC(=C2C=C1N1CCN(CC1)C)NC)C(=O)OCC)=O>>Cl.CN1CCN(CC1)C=1C=CN2C(C(=CC=C2C1)C(=O)O)=O
CC[O:15][C:13]([c:12]1[c:10](=[O:11])[n:9]2[cH:8][c:7](F)[c:6]([N:5]3[CH2:4][CH2:3][N:2]([CH3:1])[CH2:21][CH2:20]3)[cH:19][c:18]2[c:17](NC)[cH:16]1)=[O:14]>>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([c:6]2[cH:7][cH:8][n:9]3[c:10](=[O:11])[c:12]([C:13](=[O:14])[OH:15])[cH:16][cH:17][c:18]3[cH:19]2)[CH2:20][CH2:21]1
CCOC(=O)c1cc(NC)c2cc(N3CCN(C)CC3)c(F)cn2c1=O
CN1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)CC1
null
null
C1CCOC1
Deprotection
OtherReaction
d767766159eca04a31c6462e9304a3b76a67df1aacf006354a10347433d804b2
6108969b3e8e27263fe6331bef502f27a92cbd29e30aa832f75c68e6238d47c8
O=c1cccc2cc(N3CCNCC3)ccn12
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]1:[c:5]:[#7;a:6]2:[c:7]:[c;H0;D3;+0:8](-F):[c:9](-[#7:10]):[c:11]:[c:12]:2:[c;H0;D3;+0:13](-N-C):[c:14]:1>>[#7:10]-[c:9]1:[c:11]:[c:12]2:[cH;D2;+0:13]:[c:14]:[c:4](-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]):[c:5]:[#7;a:6]:2:[c:7]:[cH;D2;+0:8]:1
null
[]
75
CELSIUS
8
HOUR
A mixture of 1 g (2.75 mmol) of ethyl 7-fluoro-1-methylamino-8-(4-methylpiperazin-1-yl)-4H-quinolizin-4-one-3-carboxylate, from Step 7, in 12 mL of THF and 16.5 mL of a 0.5N aqueous solution of sodium hydroxide is heated, with stirring, at 75° C. for 8 hours. The THF is removed from the reaction mixture by distillation...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ester.Secondary amine
Carboxylic acid
c1cn2ccccc2cc1
c1cn2ccccc2cc1
C1C[NH]CC[NH]1.c1cn2ccccc2cc1
HF
C1CCOC1
75
8
CCOC(=O)c1cc(NC)c2cc(N3CCN(C)CC3)c(F)cn2c1=O>C1CCOC1>CN1CCN(c2ccn3c(=O)c(C(=O)O)ccc3c2)CC1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-d1624c7c809f4abaa8b97cad497ea554
[O-][n+]1c(F)c(F)c(F)c(F)c1F>>Cc1c(F)c(F)c(F)c(F)[n+]1[O-]
FC1=[N+](C(=C(C(=C1F)F)F)F)[O-].C[Mg]I.[Cl-].[NH4+].FC1=NC(=C(C(=C1F)F)F)F>>CC1=[N+](C(=C(C(=C1F)F)F)F)[O-]
F[c:2]1[c:3]([F:4])[c:5]([F:6])[c:7]([F:8])[c:9]([F:10])[n+:11]1[O-:12]>>[CH3:1][c:2]1[c:3]([F:4])[c:5]([F:6])[c:7]([F:8])[c:9]([F:10])[n+:11]1[O-:12]
[O-][n+]1c(F)c(F)c(F)c(F)c1F
Cc1c(F)c(F)c(F)c(F)[n+]1[O-]
null
null
C(C)OCC
Functional Group Interconversion
OtherReaction
cc6f4b6d0d543ddd6c55aed1efc961c75ac719a3837cf61a932da33e493678b7
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
c1cc[nH+]cc1
F-[c;H0;D3;+0:1](:[#7;a;+:2](-[O;-;D1;H0:3]):[c:4]):[c:5](-[F;D1;H0:6]):[c:7]>>[C;D1;H3:8]-[c;H0;D3;+0:1](:[#7;a;+:2](-[O;-;D1;H0:3]):[c:4]):[c:5](-[F;D1;H0:6]):[c:7]
null
[]
null
null
null
null
2,3,4,5,6-Pentafluoropyridine (commercially available from Aldich Chemical Co.) is oxidized to the corresponding N-oxide following the procedures described in Step 6 of Example 66. The 2,3,4,5,6-pentafluoropyridine N-oxide is treated at ambient temperature with one equivalent of methylmagnesium iodide in diethyl ether ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
C1=CC=[NH+]C=C1
C1=CC=[NH+]C=C1
C1=CC=[NH+]C=C1
null
C(C)OCC
null
null
[O-][n+]1c(F)c(F)c(F)c(F)c1F>C(C)OCC>Cc1c(F)c(F)c(F)c(F)[n+]1[O-]
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-487343b7458b49df9d5c356386d96e9c
CCI.Cc1nc(F)c(F)c(F)c1F>>CCCc1nc(F)c(F)c(F)c1F
FC=1C(=NC(=C(C1F)F)F)C.[Li+].CC(C)[N-]C(C)C.[Li+].CC(C)[N-]C(C)C.CCCCCC.C(C)I>>C(CC)C1=NC(=C(C(=C1F)F)F)F
I[CH2:2][CH3:1].[CH3:3][c:4]1[n:5][c:6]([F:7])[c:8]([F:9])[c:10]([F:11])[c:12]1[F:13]>>[CH3:1][CH2:2][CH2:3][c:4]1[n:5][c:6]([F:7])[c:8]([F:9])[c:10]([F:11])[c:12]1[F:13]
CCI.Cc1nc(F)c(F)c(F)c1F
CCCc1nc(F)c(F)c(F)c1F
null
null
[Cl-].[Na+].O.C1CCOC1
C-C Coupling
Friedel-Crafts alkylation with halide
15973705e8ad8fc52aace4e951dc2397c95f8af8fb2361e425388262f1895099
f5e5e22797736d188bba28deb76a4cee8e4fee4dca04fe24f733d2ee68a23361
c1ccncc1
I-[CH2;D2;+0:1]-[C;D1;H3:2].[CH3;D1;+0:3]-[c:4](:[c:5]):[#7;a:6]:[c:7]>>[C;D1;H3:2]-[CH2;D2;+0:1]-[CH2;D2;+0:3]-[c:4](:[c:5]):[#7;a:6]:[c:7]
null
[]
-60
CELSIUS
0.5
HOUR
A 1.5M solution of LDA in hexane (100 mL, 150 mmol) is cooled to -60° C. in an isopropyl alcohol/dry ice bath. To the stirred LDA solution, under nitrogen, is added, dropwise over a 0.5 hours period, a solution of 22.617 g (137 mmol) of 3,4,5,6-tetrafluoro-2-picoline, the product of Step 1, in 80 mL of dry THF. The rea...
10.6084/m9.figshare.5104873.v1
null
Primary halide
null
null
null
c1ccncc1
HI
[Cl-].[Na+].O.C1CCOC1
-60
0.5
CCI.Cc1nc(F)c(F)c(F)c1F>[Cl-].[Na+].O.C1CCOC1>CCCc1nc(F)c(F)c(F)c1F
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-ab0b347450d44f97b1ec59d5fd17f704
CCOC(=O)C1C=C(CC)C2=C(F)C(F)(Cl)C(F)=C(F)N2C1=O.CN1CCNCC1>>CCOC(=O)c1cc(CC)c2c(F)c(N3CCN(C)CC3)c(F)c(F)n2c1=O
ClC1(C(=C(N2C(C(C=C(C2=C1F)CC)C(=O)OCC)=O)F)F)F.CN1CCNCC1>>C(C)C=1C=C(C(N2C(=C(C(=C(C12)F)N1CCN(CC1)C)F)F)=O)C(=O)OCC
F[C:14]1(Cl)[C:12]([F:13])=[C:11]2[C:8]([CH2:9][CH3:10])=[CH:7][CH:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[C:27](=[O:28])[N:26]2[C:24]([F:25])=[C:22]1[F:23].[NH:15]1[CH2:16][CH2:17][N:18]([CH3:19])[CH2:20][CH2:21]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([CH2:9][CH3:10])[c:11]2[c:12]([F:13])[c:14]([N:15]3[CH2:1...
CCOC(=O)C1C=C(CC)C2=C(F)C(F)(Cl)C(F)=C(F)N2C1=O.CN1CCNCC1
CCOC(=O)c1cc(CC)c2c(F)c(N3CCN(C)CC3)c(F)c(F)n2c1=O
null
null
N1=CC=CC=C1
Aromatic Heterocycle Formation
OtherReaction
61141502804def142624ebf6de9457c7ce12c3d0914157ecbf5cc024f28f95db
46bebd2a54663dfaa5a326dc4633e4fab960d5e57724fa2874aa798ef8a6827f
O=c1cccc2cc(N3CCNCC3)ccn12
Cl-[C;H0;D4;+0:1]1(-F)-[C;H0;D3;+0:2](-[F;D1;H0:3])=[C;H0;D3;+0:4]2-[C;H0;D3;+0:5](-[C:6]-[C;D1;H3:7])=[CH;D2;+0:8]-[CH;D3;+0:9](-[C:10](=[O;D1;H0:11])-[#8:12]-[C:13])-[C;H0;D3;+0:14](=[O;D1;H0:15])-[N;H0;D3;+0:16]-2-[C;H0;D3;+0:17](-[F;D1;H0:18])=[C;H0;D3;+0:19]-1-[F;D1;H0:20].[#7:21]1-[C:22]-[C:23]-[NH;D2;+0:24]-[C:2...
null
[]
85
CELSIUS
null
null
Ethyl 8-chloro-1-ethyl-6,7,8,9-tetrafluoro-4H-quinolizin-4-one-3-carboxylate (317 mg, 1.0 mmol), from Step 4, is dissolved in 5 mL of dry pyridine under a nitrogen atmosphere. To the resultant solution is added 2 mL (2.0 mmol) of N-methylpiperazine and the stirred reaction mixture is heated at 85° C. for 2.5 hours. The...
10.6084/m9.figshare.5104873.v1
null
Enamine.Enamine.Tertiary halide.Tertiary halide.Alkenyl halide.Alkenyl halide.Alkenyl halide.Ester.Tertiary amide.Secondary amine
Aromatic halide.Aromatic halide.Aromatic halide.Ester.Tertiary amine
C1=CN2CCC=CC2=CC1.C1CNCC[NH]1
c1ccn2ccccc2c1.C1C[NH]CC[NH]1
c1ccn2ccccc2c1.C1C[NH]CC[NH]1
HF
N1=CC=CC=C1
85
null
CCOC(=O)C1C=C(CC)C2=C(F)C(F)(Cl)C(F)=C(F)N2C1=O.CN1CCNCC1>N1=CC=CC=C1>CCOC(=O)c1cc(CC)c2c(F)c(N3CCN(C)CC3)c(F)c(F)n2c1=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-bc06e3b96a4d464db4a5d7e744be556b
CCOC(=O)c1cc(CC)c2c(F)c(N3CCN(C)CC3)c(F)c(F)n2c1=O>>CCc1cc(C(=O)O)c(=O)n2c(F)c(F)c(N3CCN(C)CC3)c(F)c12
Cl.C(C)C=1C=C(C(N2C(=C(C(=C(C12)F)N1CCN(CC1)C)F)F)=O)C(=O)OCC.[OH-].[Na+]>>Cl.C(C)C=1C=C(C(N2C(=C(C(=C(C12)F)N1CCN(CC1)C)F)F)=O)C(=O)O
CC[O:8][C:6]([c:5]1[cH:4][c:3]([CH2:2][CH3:1])[c:26]2[n:11]([c:9]1=[O:10])[c:12]([F:13])[c:14]([F:15])[c:16]([N:17]1[CH2:18][CH2:19][N:20]([CH3:21])[CH2:22][CH2:23]1)[c:24]2[F:25])=[O:7]>>[CH3:1][CH2:2][c:3]1[cH:4][c:5]([C:6](=[O:7])[OH:8])[c:9](=[O:10])[n:11]2[c:12]([F:13])[c:14]([F:15])[c:16]([N:17]3[CH2:18][CH2:19][...
CCOC(=O)c1cc(CC)c2c(F)c(N3CCN(C)CC3)c(F)c(F)n2c1=O
CCc1cc(C(=O)O)c(=O)n2c(F)c(F)c(N3CCN(C)CC3)c(F)c12
null
null
C1CCOC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=c1cccc2cc(N3CCNCC3)ccn12
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]
null
[]
75
CELSIUS
4.5
HOUR
To a solution of 199 mg (0.5 mmol) of ethyl 1-ethyl-8-(4-methylpiperazin-1-yl)-6,7,9-trifluoro-4H-quinolizin-4-one-3-carboxylate, from Step 5, in 4 mL of THF is added 4.0 mL of a 1.0N aqueous sodium hydroxide solution and the reaction mixture is heated, with stirring, at 75° C. for 4.5 hours. The reaction mixture is co...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccn2ccccc2c1.C1C[NH]CC[NH]1
Other
C1CCOC1
75
4.5
CCOC(=O)c1cc(CC)c2c(F)c(N3CCN(C)CC3)c(F)c(F)n2c1=O>C1CCOC1>CCc1cc(C(=O)O)c(=O)n2c(F)c(F)c(N3CCN(C)CC3)c(F)c12
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-4f295b3d715849a297bcad06075e2348
CC(COC1CCCCO1)c1ncc(F)c(Cl)c1F>>CC(CO)c1ncc(F)c(Cl)c1F
ClC1=C(C(=NC=C1F)C(COC1OCCCC1)C)F.O.C(C)(=O)O>>ClC1=C(C(=NC=C1F)C(CO)C)F
C1CCC([O:4][CH2:3][CH:2]([CH3:1])[c:5]2[n:6][cH:7][c:8]([F:9])[c:10]([Cl:11])[c:12]2[F:13])OC1>>[CH3:1][CH:2]([CH2:3][OH:4])[c:5]1[n:6][cH:7][c:8]([F:9])[c:10]([Cl:11])[c:12]1[F:13]
CC(COC1CCCCO1)c1ncc(F)c(Cl)c1F
CC(CO)c1ncc(F)c(Cl)c1F
null
null
C1CCOC1
Reduction
Ether cleavage to primary alcohol
69ac283008defddd09d640f7879e86f66dd29371b5c835a2facf24163ef14e9f
a4561cbdd42f56679299e19ea8b11070a39a15f6a95fb8a877e677f11b7ff57f
c1ccncc1
[C:1]-[C:2]-[O;H0;D2;+0:3]-C1-C-C-C-C-O-1>>[C:1]-[C:2]-[OH;D1;+0:3]
null
[]
45
CELSIUS
null
null
The product of Step 1 is dissolved in 200 mL of 2:1 THF:water and to this solution is added 6 mL of acetic acid. The reaction mixture is heated at 45° C. for approximately 5 hours. The THF is removed under reduced pressure and the aqueous reaction mixture is adjusted to a pH in the range of 8 to 9 with 10% sodium carbo...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether
Primary alcohol
C1CCOCC1
null
c1ccncc1
HO-
C1CCOC1
45
null
CC(COC1CCCCO1)c1ncc(F)c(Cl)c1F>C1CCOC1>CC(CO)c1ncc(F)c(Cl)c1F
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-c191750ca7b54fdb8dafaf0853defb9d
CC(C)(C)Oc1cc(F)nc(F)c1F.OO>>CC(C)(C)Oc1c(O)c(F)nc(F)c1F
C(C)(C)(C)OC1=C(C(=NC(=C1)F)F)F.[Li+].CC(C)[N-]C(C)C.OO.[OH-].[Na+].COB(OC)OC>>C(C)(C)(C)OC1=C(C(=NC(=C1O)F)F)F
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][c:6]1[cH:7][c:9]([F:10])[n:11][c:12]([F:13])[c:14]1[F:15].O[OH:8]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][c:6]1[c:7]([OH:8])[c:9]([F:10])[n:11][c:12]([F:13])[c:14]1[F:15]
CC(C)(C)Oc1cc(F)nc(F)c1F.OO
CC(C)(C)Oc1c(O)c(F)nc(F)c1F
null
null
C(C)(=O)O.C1CCOC1
Heteroatom Alkylation and Arylation
OtherReaction
1d486e404d15e1f03f247400e5680334f540a293783abe66ffa8f2f1b3c56e68
a2fdf414569b219d462bc05c91ebf31e5426b96645f5c78cb091f50cc92fc345
c1ccncc1
O-[OH;D1;+0:1].[C;D1;H3:2]-[C:3](-[C;D1;H3:4])(-[C;D1;H3:5])-[#8:6]-[c:7]1:[c:8]:[c:9]:[#7;a:10]:[c:11](-[F;D1;H0:12]):[cH;D2;+0:13]:1>>[C;D1;H3:2]-[C:3](-[C;D1;H3:4])(-[C;D1;H3:5])-[#8:6]-[c:7]1:[c:8]:[c:9]:[#7;a:10]:[c:11](-[F;D1;H0:12]):[c;H0;D3;+0:13]:1-[OH;D1;+0:1]
null
[]
-78
CELSIUS
30
MINUTE
A 11.16 g (54.39 mmol) sample of 4-t-butoxy-2,3,6-trifluoropyridine, from Example 253 step b above, was dissolved in 50 mL of THF, and the solution was cooled to -78° C. To this solution was added LDA (65.6 mmol) with stirring for 30 min, during which a solid preciptated. To this mixture was added 7.5 mL of trimethoxyb...
10.6084/m9.figshare.5104873.v1
null
Peroxide
Aromatic alcohol
c1ccncc1
c1ccncc1
c1ccncc1
HO-
C(C)(=O)O.C1CCOC1
-78
0.5
CC(C)(C)Oc1cc(F)nc(F)c1F.OO>C(C)(=O)O.C1CCOC1>CC(C)(C)Oc1c(O)c(F)nc(F)c1F
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-60ba32da8a3a420db576adcfd7bcef8c
CC(C)(C)Oc1c(O)c(F)nc(F)c1F.CO>>COc1c(F)nc(F)c(F)c1OC(C)(C)C
CCOC(=O)/N=N/C(=O)OCC.C(C)(C)(C)OC1=C(C(=NC(=C1O)F)F)F.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.CO>>C(C)(C)(C)OC1=C(C(=NC(=C1OC)F)F)F
[OH:2][c:3]1[c:4]([F:5])[n:6][c:7]([F:8])[c:9]([F:10])[c:11]1[O:12][C:13]([CH3:14])([CH3:15])[CH3:16].O[CH3:1]>>[CH3:1][O:2][c:3]1[c:4]([F:5])[n:6][c:7]([F:8])[c:9]([F:10])[c:11]1[O:12][C:13]([CH3:14])([CH3:15])[CH3:16]
CC(C)(C)Oc1c(O)c(F)nc(F)c1F.CO
COc1c(F)nc(F)c(F)c1OC(C)(C)C
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
4622e7934dd5328af1014056d8882932e5f303d08f873e671539ebf0ad57f848
51e77d0fe280879eec2f84298441067b61501ac5af19ab94008f56517f7456b2
c1ccncc1
O-[CH3;D1;+0:1].[F;D1;H0:2]-[c:3](:[#7;a:4]:[c:5]):[c:6](-[OH;D1;+0:7]):[c:8]>>[CH3;D1;+0:1]-[O;H0;D2;+0:7]-[c:6](:[c:8]):[c:3](-[F;D1;H0:2]):[#7;a:4]:[c:5]
85.7
[{"value": 85.7, "product": "C(C)(C)(C)OC1=C(C(=NC(=C1OC)F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
To a solution of 237 mg (1.07 mmol) of 4-t-butoxy-2,3,6-trifluoro-5-hydroxypyridine, from step 275a above, in 3 mL of anhydrous THF was added 335 mg (1.277 mmol) of triphenyl phosphine and 0.060 mL (1.48 mmol) of methanol. To this solution was added 0.200 mL (1.270 mmol) of DEAD dropwise at room temperature. The reacti...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol.Methanol
Ether
null
null
c1ccncc1
HO-
C1CCOC1
null
0.166667
CC(C)(C)Oc1c(O)c(F)nc(F)c1F.CO>C1CCOC1>COc1c(F)nc(F)c(F)c1OC(C)(C)C
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-42ec8884ab714360a71d7169f934632f
CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O.C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CCNC1>>Cc1c(N2CC[C@@H]([C@H](C)N)C2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12.Cl
C(C)OC(=O)C1=CC(=C2C(=C(C(=CN2C1=O)F)Cl)C)C1CC1.C(C)(C)(C)OC(=O)N[C@@H](C)[C@H]1CNCC1>>Cl.N[C@@H](C)[C@H]1CN(CC1)C=1C(=CN2C(C(=CC(=C2C1C)C1CC1)C(=O)O)=O)F
CC[O:21][C:19]([c:18]1[c:16](=[O:17])[n:15]2[cH:14][c:12]([F:13])[c:3]([Cl:28])[c:2]([CH3:1])[c:27]2[c:23]([CH:24]2[CH2:25][CH2:26]2)[cH:22]1)=[O:20].CC(C)(C)OC(=O)[NH:10][C@H:8]([C@@H:7]1[CH2:6][CH2:5][NH:4][CH2:11]1)[CH3:9]>>[CH3:1][c:2]1[c:3]([N:4]2[CH2:5][CH2:6][C@@H:7]([C@H:8]([CH3:9])[NH2:10])[CH2:11]2)[c:12]([F:...
CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O.C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CCNC1
Cc1c(N2CC[C@@H]([C@H](C)N)C2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12.Cl
null
null
C(C)#N
Heteroatom Alkylation and Arylation
OtherReaction
b96865a2ff8714677ca5bb9121091de64fb42c9ead83b6dbe92c6b4491a8f051
5c530bc185fdf54956090e5ff31b4625247366cd666dcae789cfd53ed04cb8aa
O=c1ccc(C2CC2)c2cc(N3CCCC3)ccn12
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C;D1;H3:3])-[C:4]1-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]-1.C-C-[O;H0;D2;+0:9]-[C:10](=[O;D1;H0:11])-[c:12]:[c:13]:[#7;a:14]1:[c:15]:[c:16](-[F;D1;H0:17]):[c;H0;D3;+0:18](-[Cl;H0;D1;+0:19]):[c:20](-[C;D1;H3:21]):[c:22]:1:[c:23]>>[C;D1;H3:21]-[c:20]1:[c:22](:[c:23]):[#7;a:14](:[c:15]:[c:...
null
[]
null
null
null
null
A sample of 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester, from Example 253i above, was dissolved in anhydrous acetonitrile, reacted with (3R,1S)-3-(1-(t-butoxycarbonylamino)ethyl)pyrrolidine (prepared as described by Schroeder et al., J. Heterocyclic Chem., 29:1481-1498 (1...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Carbamic ester.Ester.Ether.Secondary amine.Boc
Carboxylic acid.Primary amine.Tertiary amine
c1ccn2ccccc2c1.C1CCNC1
C1CC[NH]C1.c1ccn2ccccc2c1
C1CC[NH]C1.c1ccn2ccccc2c1.C1CC1
HO-
C(C)#N
null
null
CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O.C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CCNC1>C(C)#N>Cc1c(N2CC[C@@H]([C@H](C)N)C2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12.Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-55cfd45f05674e829002cb383c59d3b6
CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O.C[C@@H](NC(=O)OC(C)(C)C)[C@H]1CCNC1>>Cc1c(N2CC[C@H]([C@@H](C)N)C2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12.Cl
C(C)OC(=O)C1=CC(=C2C(=C(C(=CN2C1=O)F)Cl)C)C1CC1.C(=O)(O)[O-].[Na+].C(C)(C)(C)OC(=O)N[C@H](C)[C@@H]1CNCC1>>Cl.N[C@H](C)[C@@H]1CN(CC1)C=1C(=CN2C(C(=CC(=C2C1C)C1CC1)C(=O)O)=O)F
CC[O:21][C:19]([c:18]1[c:16](=[O:17])[n:15]2[cH:14][c:12]([F:13])[c:3]([Cl:28])[c:2]([CH3:1])[c:27]2[c:23]([CH:24]2[CH2:25][CH2:26]2)[cH:22]1)=[O:20].CC(C)(C)OC(=O)[NH:10][C@@H:8]([C@H:7]1[CH2:6][CH2:5][NH:4][CH2:11]1)[CH3:9]>>[CH3:1][c:2]1[c:3]([N:4]2[CH2:5][CH2:6][C@H:7]([C@@H:8]([CH3:9])[NH2:10])[CH2:11]2)[c:12]([F:...
CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O.C[C@@H](NC(=O)OC(C)(C)C)[C@H]1CCNC1
Cc1c(N2CC[C@H]([C@@H](C)N)C2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12.Cl
null
null
C(C)#N
Heteroatom Alkylation and Arylation
OtherReaction
b96865a2ff8714677ca5bb9121091de64fb42c9ead83b6dbe92c6b4491a8f051
5c530bc185fdf54956090e5ff31b4625247366cd666dcae789cfd53ed04cb8aa
O=c1ccc(C2CC2)c2cc(N3CCCC3)ccn12
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C;D1;H3:3])-[C:4]1-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]-1.C-C-[O;H0;D2;+0:9]-[C:10](=[O;D1;H0:11])-[c:12]:[c:13]:[#7;a:14]1:[c:15]:[c:16](-[F;D1;H0:17]):[c;H0;D3;+0:18](-[Cl;H0;D1;+0:19]):[c:20](-[C;D1;H3:21]):[c:22]:1:[c:23]>>[C;D1;H3:21]-[c:20]1:[c:22](:[c:23]):[#7;a:14](:[c:15]:[c:...
null
[]
null
null
null
null
A 0.44 g sample of 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester, from Example 253i above, and 1.51 g of NaHCO3 were dissolved in 40 mL of anhydrous acetonitrile, reacted with (3S,1R)-3-(1-(t-butoxycarbonylamino)ethyl)pyrrolidine (1.06 g, prepared as described by Schroeder ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Carbamic ester.Ester.Ether.Secondary amine.Boc
Carboxylic acid.Primary amine.Tertiary amine
c1ccn2ccccc2c1.C1CCNC1
C1CC[NH]C1.c1ccn2ccccc2c1
C1CC[NH]C1.c1ccn2ccccc2c1.C1CC1
HO-
C(C)#N
null
null
CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O.C[C@@H](NC(=O)OC(C)(C)C)[C@H]1CCNC1>C(C)#N>Cc1c(N2CC[C@H]([C@@H](C)N)C2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12.Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-f80d09c9ce4641f588bcb7b3d9cdf66d
CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O.C[C@@H](NC(=O)OC(C)(C)C)[C@@H]1CCNC1>>Cc1cc(F)cn2c(=O)c(C(=O)O)c(N3CCC(C(C)N)C3)c(C3CC3)c12.Cl
C(C)OC(=O)C1=CC(=C2C(=C(C(=CN2C1=O)F)Cl)C)C1CC1.C([O-])(O)=O.[Na+].C(C)(C)(C)OC(=O)N[C@H](C)[C@H]1CNCC1>>Cl.NC(C)C1CN(CC1)C=1C(=C2C(=CC(=CN2C(C1C(=O)O)=O)F)C)C1CC1
CC[O:13][C:11]([c:10]1[c:8](=[O:9])[n:7]2[cH:6][c:4]([F:5])[c:3]([Cl:28])[c:2]([CH3:1])[c:27]2[c:23]([CH:24]2[CH2:25][CH2:26]2)[cH:14]1)=[O:12].CC(C)(C)OC(=O)[NH:21][C@@H:19]([C@@H:18]1[CH2:17][CH2:16][NH:15][CH2:22]1)[CH3:20]>>[CH3:1][c:2]1[cH:3][c:4]([F:5])[cH:6][n:7]2[c:8](=[O:9])[c:10]([C:11](=[O:12])[OH:13])[c:14]...
CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O.C[C@@H](NC(=O)OC(C)(C)C)[C@@H]1CCNC1
Cc1cc(F)cn2c(=O)c(C(=O)O)c(N3CCC(C(C)N)C3)c(C3CC3)c12.Cl
null
null
C(C)#N
Heteroatom Alkylation and Arylation
OtherReaction
b96865a2ff8714677ca5bb9121091de64fb42c9ead83b6dbe92c6b4491a8f051
5c530bc185fdf54956090e5ff31b4625247366cd666dcae789cfd53ed04cb8aa
O=c1cc(N2CCCC2)c(C2CC2)c2ccccn12
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C@H;D3;+0:2](-[C;D1;H3:3])-[C@@H;D3;+0:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-1.C-C-[O;H0;D2;+0:9]-[C:10](=[O;D1;H0:11])-[c:12]1:[cH;D2;+0:13]:[c:14](-[C:15]):[c:16]2:[#7;a:17](:[c:18]:[c:19](-[F;D1;H0:20]):[c;H0;D3;+0:21](-[Cl;H0;D1;+0:22]):[c:23]:2-[C;D1;H3:24]):[c:25]:1=[O;D1;H0:26]>>[C...
null
[]
null
null
null
null
A 0.35 g sample of 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester, from Example 253i above, and 0.73 g of sodium bicarbonate were dissolved in 24 mL of anhydrous acetonitrile, reacted with (3R,1R)-3-(1-(t-butoxycarbonylamino)ethyl)-pyrrolidine (0.51 g, prepared as described ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Carbamic ester.Ester.Ether.Secondary amine.Boc
Carboxylic acid.Primary amine.Tertiary amine
c1ccn2ccccc2c1.C1CCNC1
c1ccn2ccccc2c1.C1CC[NH]C1
c1ccn2ccccc2c1.C1CC[NH]C1.C1CC1
HO-
C(C)#N
null
null
CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O.C[C@@H](NC(=O)OC(C)(C)C)[C@@H]1CCNC1>C(C)#N>Cc1cc(F)cn2c(=O)c(C(=O)O)c(N3CCC(C(C)N)C3)c(C3CC3)c12.Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-021e1069b0ae4865bfe08ff43a38ea27
C1CCN(C2CCNCC2)CC1.CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O>>Cc1c(N2CCC(N3CCCCC3)CC2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12
C(C)OC(=O)C1=CC(=C2C(=C(C(=CN2C1=O)F)Cl)C)C1CC1.N1(CCCCC1)C1CCNCC1>>N1(CCCCC1)C1CCN(CC1)C=1C(=CN2C(C(=CC(=C2C1C)C1CC1)C(=O)O)=O)F
[NH:4]1[CH2:5][CH2:6][CH:7]([N:8]2[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]2)[CH2:14][CH2:15]1.CC[O:25][C:23]([c:22]1[c:20](=[O:21])[n:19]2[cH:18][c:16]([F:17])[c:3](Cl)[c:2]([CH3:1])[c:31]2[c:27]([CH:28]2[CH2:29][CH2:30]2)[cH:26]1)=[O:24]>>[CH3:1][c:2]1[c:3]([N:4]2[CH2:5][CH2:6][CH:7]([N:8]3[CH2:9][CH2:10][CH2:11][CH2:1...
C1CCN(C2CCNCC2)CC1.CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O
Cc1c(N2CCC(N3CCCCC3)CC2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12
null
null
C(C)#N
Heteroatom Alkylation and Arylation
OtherReaction
75e3478f1935539f46d5bed9d67d6223d61ee486643b0274563c38d0f0705c86
154ad2504fb7aaca0f52c4b8eebdfca329f4106b95adc3c71ff059886f074b58
O=c1ccc(C2CC2)c2cc(N3CCC(N4CCCCC4)CC3)ccn12
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]:[#7;a:6]1:[c:7]:[c:8](-[F;D1;H0:9]):[c;H0;D3;+0:10](-Cl):[c:11](-[C;D1;H3:12]):[c:13]:1:[c:14].[C:15]-[C:16]-[NH;D2;+0:17]-[C:18]-[C:19]>>[C:15]-[C:16]-[N;H0;D3;+0:17](-[c;H0;D3;+0:10]1:[c:8](-[F;D1;H0:9]):[c:7]:[#7;a:6](:[c:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]):[...
null
[]
null
null
null
null
A 70 mg sample of 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester, from Example 253i above, was dissolved in 2 mL of anhydrous acetonitrile, reacted with 4-(1-piperidyl)piperidine (70 mg, 0.4 mmol, Aldrich Chem. Co.), and carried forward as described in Example 253j-k to give...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ester.Secondary amine
Carboxylic acid.Tertiary amine
C1CCNCC1.c1ccn2ccccc2c1
C1CC[NH]CC1.c1ccn2ccccc2c1
C1CC[NH]CC1.C1CC[NH]CC1.c1ccn2ccccc2c1.C1CC1
HCl
C(C)#N
null
null
C1CCN(C2CCNCC2)CC1.CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O>C(C)#N>Cc1c(N2CCC(N3CCCCC3)CC2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-972b3424b54942c0a0dc54962740941f
CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O.c1ccc(N2CCNCC2)nc1>>Cc1c(N2CCN(c3ccccn3)CC2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12
C(C)OC(=O)C1=CC(=C2C(=C(C(=CN2C1=O)F)Cl)C)C1CC1.N1=C(C=CC=C1)N1CCNCC1>>N1=C(C=CC=C1)N1CCN(CC1)C=1C(=CN2C(C(=CC(=C2C1C)C1CC1)C(=O)O)=O)F
CC[O:25][C:23]([c:22]1[c:20](=[O:21])[n:19]2[cH:18][c:16]([F:17])[c:3](Cl)[c:2]([CH3:1])[c:31]2[c:27]([CH:28]2[CH2:29][CH2:30]2)[cH:26]1)=[O:24].[NH:4]1[CH2:5][CH2:6][N:7]([c:8]2[cH:9][cH:10][cH:11][cH:12][n:13]2)[CH2:14][CH2:15]1>>[CH3:1][c:2]1[c:3]([N:4]2[CH2:5][CH2:6][N:7]([c:8]3[cH:9][cH:10][cH:11][cH:12][n:13]3)[C...
CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O.c1ccc(N2CCNCC2)nc1
Cc1c(N2CCN(c3ccccn3)CC2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12
null
null
C(C)#N
Heteroatom Alkylation and Arylation
OtherReaction
3d13f06a25d11dec98bfced8d30fa8db832cfa5df664b10802b8dba845979727
154ad2504fb7aaca0f52c4b8eebdfca329f4106b95adc3c71ff059886f074b58
O=c1ccc(C2CC2)c2cc(N3CCN(c4ccccn4)CC3)ccn12
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[c:5]:[#7;a:6]1:[c:7]:[c:8](-[F;D1;H0:9]):[c;H0;D3;+0:10](-Cl):[c:11](-[C;D1;H3:12]):[c:13]:1:[c:14].[#7:15]1-[C:16]-[C:17]-[NH;D2;+0:18]-[C:19]-[C:20]-1>>[C;D1;H3:12]-[c:11]1:[c:13](:[c:14]):[#7;a:6](:[c:7]:[c:8](-[F;D1;H0:9]):[c;H0;D3;+0:10]:1-[N;H0;D3;+0:18]1-[C:17]-[C:16...
null
[]
null
null
null
null
A 60 mg sample of 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester, from Example 253i above, was dissolved in 2 mL of anhydrous acetonitrile, reacted with 4-(2-pyridyl)piperazine (63.5 mg, 0.39 mmol, Aldrich Chem. Co.), and carried forward as described in Example 253j-k to giv...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ester.Secondary amine
Carboxylic acid.Tertiary amine
c1ccn2ccccc2c1.C1CNCC[NH]1
C1C[NH]CC[NH]1.c1ccn2ccccc2c1
C1C[NH]CC[NH]1.c1ccncc1.c1ccn2ccccc2c1.C1CC1
HCl
C(C)#N
null
null
CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O.c1ccc(N2CCNCC2)nc1>C(C)#N>Cc1c(N2CCN(c3ccccn3)CC2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-92c1e74f55654031bf26bcc5f6384595
C1CCNC1.CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O>>Cc1c(N2CCC(C(C)(C)N)C2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12.Cl
C(C)OC(=O)C1=CC(=C2C(=C(C(=CN2C1=O)F)Cl)C)C1CC1.N1CCCC1>>Cl.NC(C)(C)C1CN(CC1)C=1C(=CN2C(C(=CC(=C2C1C)C1CC1)C(=O)O)=O)F
[NH:4]1[CH2:5][CH2:6][CH2:7][CH2:12]1.[CH3:1][c:2]1[c:3]([Cl:29])[c:13]([F:14])[cH:15][n:16]2[c:17](=[O:18])[c:19]([C:20](=[O:21])[O:22][CH2:8][CH3:9])[cH:23][c:24]([CH:25]3[CH2:10][CH2:26]3)[c:28]12>>[CH3:1][c:2]1[c:3]([N:4]2[CH2:5][CH2:6][CH:7]([C:8]([CH3:9])([CH3:10])[NH2:11])[CH2:12]2)[c:13]([F:14])[cH:15][n:16]2[c...
C1CCNC1.CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O
Cc1c(N2CCC(C(C)(C)N)C2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12.Cl
null
null
C(C)#N
Functional Group Addition
OtherReaction
2a14acf5dad08302fea9e0bd4232a3eaeb821e0070a4f67f5349da5b06b8412a
9483057e46e532308f07004ea2e319dd166b11d42f3c6073c033a07678c4faf6
O=c1ccc(C2CC2)c2cc(N3CCCC3)ccn12
[C;D1;H3:1]-[c:2]1:[c:3]2:[#7;a:4](:[c:5]:[c:6](-[F;D1;H0:7]):[c;H0;D3;+0:8]:1-[Cl;H0;D1;+0:9]):[c:10]:[c:11](-[C:12](=[O;D1;H0:13])-[O;H0;D2;+0:14]-[CH2;D2;+0:15]-[C;D1;H3:16]):[c:17]:[c:18]:2-[CH;D3;+0:19]1-[CH2;D2;+0:20]-[CH2;D2;+0:21]-1.[C:22]1-[CH2;D2;+0:23]-[C:24]-[C:25]-[NH;D2;+0:26]-1>>[C;D1;H3:1]-[c:2]1:[c:3]2...
null
[]
null
null
null
null
A 150 mg sample of 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester, from Example 253i above, was dissolved in 2 mL of anhydrous acetonitrile, reacted with 1-amino-1-methylethyl)pyrrolidine (155 mg, 0.77 mmol, prepared by standard method from the free base described by Hayakaw...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ester.Secondary amine
Carboxylic acid.Primary amine.Tertiary amine
C1CCNC1.c1ccn2ccccc2c1.C1CC1
C1CC[NH]C1.c1ccn2ccccc2c1.C1CC1
C1CC[NH]C1.c1ccn2ccccc2c1.C1CC1
Other
C(C)#N
null
null
C1CCNC1.CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O>C(C)#N>Cc1c(N2CCC(C(C)(C)N)C2)c(F)cn2c(=O)c(C(=O)O)cc(C3CC3)c12.Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-1497b876ea1b4e33b1825cfea95b6d86
CCCC(NC(=O)OC(C)(C)C)C1CCNC1.CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O>>CCCC(N)C1CCN(c2c(F)cn3c(=O)c(C(=O)O)cc(C4CC4)c3c2C)C1.Cl
C(C)OC(=O)C1=CC(=C2C(=C(C(=CN2C1=O)F)Cl)C)C1CC1.C(=O)(OC(C)(C)C)NC(CCC)C1CNCC1>>Cl.NC(CCC)C1CN(CC1)C=1C(=CN2C(C(=CC(=C2C1C)C1CC1)C(=O)O)=O)F
CC(C)(C)OC(=O)[NH:5][CH:4]([CH2:3][CH2:2][CH3:1])[CH:6]1[CH2:7][CH2:8][NH:9][CH2:29]1.CC[O:20][C:18]([c:17]1[c:15](=[O:16])[n:14]2[cH:13][c:11]([F:12])[c:10]([Cl:30])[c:27]([CH3:28])[c:26]2[c:22]([CH:23]2[CH2:24][CH2:25]2)[cH:21]1)=[O:19]>>[CH3:1][CH2:2][CH2:3][CH:4]([NH2:5])[CH:6]1[CH2:7][CH2:8][N:9]([c:10]2[c:11]([F:...
CCCC(NC(=O)OC(C)(C)C)C1CCNC1.CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O
CCCC(N)C1CCN(c2c(F)cn3c(=O)c(C(=O)O)cc(C4CC4)c3c2C)C1.Cl
null
null
C(C)#N
Heteroatom Alkylation and Arylation
OtherReaction
b96865a2ff8714677ca5bb9121091de64fb42c9ead83b6dbe92c6b4491a8f051
5c530bc185fdf54956090e5ff31b4625247366cd666dcae789cfd53ed04cb8aa
O=c1ccc(C2CC2)c2cc(N3CCCC3)ccn12
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C:3])-[C:4]1-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]-1.C-C-[O;H0;D2;+0:9]-[C:10](=[O;D1;H0:11])-[c:12]:[c:13]:[#7;a:14]1:[c:15]:[c:16](-[F;D1;H0:17]):[c;H0;D3;+0:18](-[Cl;H0;D1;+0:19]):[c:20](-[C;D1;H3:21]):[c:22]:1:[c:23]>>[C:3]-[C:2](-[NH2;D1;+0:1])-[C:4]1-[C:5]-[N;H0;D3;+0:6](-[c;H0;D...
null
[]
null
null
null
null
A 238 mg sample of 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester, from Example 253i above, was dissolved in 5 mL of anhydrous acetonitrile, reacted with 3-(1-(N-BOC-amino)butyl)pyrrolidine (620 mg, 1.83 mmol, prepared in step 314d above), and carried forward as described in...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Carbamic ester.Ester.Ether.Secondary amine.Boc
Carboxylic acid.Primary amine.Tertiary amine
C1CCNC1.c1ccn2ccccc2c1
C1CC[NH]C1.c1ccn2ccccc2c1
C1CC[NH]C1.c1ccn2ccccc2c1.C1CC1
HO-
C(C)#N
null
null
CCCC(NC(=O)OC(C)(C)C)C1CCNC1.CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O>C(C)#N>CCCC(N)C1CCN(c2c(F)cn3c(=O)c(C(=O)O)cc(C4CC4)c3c2C)C1.Cl
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-93761b963a124e92971caa48a87616c1
Nc1ccc2[nH]ccc2c1>>NC1CCC2NCCC2C1
NC=1C=C2C=CNC2=CC1>>NC1CC2CCNC2CC1
[NH2:1][c:2]1[cH:3][cH:4][c:5]2[nH:6][cH:7][cH:8][c:9]2[cH:10]1>>[NH2:1][CH:2]1[CH2:3][CH2:4][CH:5]2[NH:6][CH2:7][CH2:8][CH:9]2[CH2:10]1
Nc1ccc2[nH]ccc2c1
NC1CCC2NCCC2C1
null
null
C(C)(=O)O
Reduction
OtherReaction
1a8bda49366775c1ecaa868ff827f72b98c3b352605f1d6dd7d013f9a334a693
2b7f370a519e29b4dede190aa36b37f30822496e32f2c8bfa9736e631bde52e2
C1CCC2NCCC2C1
[N;D1;H2:1]-[c;H0;D3;+0:2]1:[cH;D2;+0:3]:[c;H0;D3;+0:4]2:[cH;D2;+0:5]:[cH;D2;+0:6]:[nH;D2;+0:7]:[c;H0;D3;+0:8]:2:[cH;D2;+0:9]:[cH;D2;+0:10]:1>>[N;D1;H2:1]-[CH;D3;+0:2]1-[CH2;D2;+0:3]-[CH;D3;+0:4]2-[CH2;D2;+0:5]-[CH2;D2;+0:6]-[NH;D2;+0:7]-[CH;D3;+0:8]-2-[CH2;D2;+0:9]-[CH2;D2;+0:10]-1
null
[]
null
null
null
null
A 1.0 g sample of 5-aminoindole was hydrogenated at 4 atm H2 in 50 mL of acetic acid over 2 g of Pt2O at room temperature for 90 hours. The solution was filtered, and the solvent was removed Conditions: See reaction.notes.procedure_details. Workup: The solution was filtered; the solvent was removed
10.6084/m9.figshare.5104873.v1
null
null
Secondary amine
c1ccc2[nH]ccc2c1
C1CCC2NCCC2C1
C1CCC2NCCC2C1
null
C(C)(=O)O
null
null
Nc1ccc2[nH]ccc2c1>C(C)(=O)O>NC1CCC2NCCC2C1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-9c6f52c74e1f4a55a7103d040ea32d13
O=C(NC1CCN(Cc2ccccc2)C1)C(F)(F)F>>FC(F)(F)CNC1CCN(Cc2ccccc2)C1
C(C1=CC=CC=C1)N1CC(CC1)NC(C(F)(F)F)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>>C(C1=CC=CC=C1)N1CC(CC1)NCC(F)(F)F
O=[C:5]([C:2]([F:1])([F:3])[F:4])[NH:6][CH:7]1[CH2:8][CH2:9][N:10]([CH2:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[CH2:18]1>>[F:1][C:2]([F:3])([F:4])[CH2:5][NH:6][CH:7]1[CH2:8][CH2:9][N:10]([CH2:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[CH2:18]1
O=C(NC1CCN(Cc2ccccc2)C1)C(F)(F)F
FC(F)(F)CNC1CCN(Cc2ccccc2)C1
null
null
CCOCC
Reduction
Reduction of secondary amides to amines
85b757f1833edc9e5c6365ee6b904683f414e7b9a5f9bfcfd7addca401447058
ab40188eef2f825df7003af0ffae31d0ce53d126542122535627d3d354cbc9fe
c1ccc(CN2CCCC2)cc1
O=[C;H0;D3;+0:1](-[#7:2]-[C:3])-[C:4](-[F;D1;H0:5])(-[F;D1;H0:6])-[F;D1;H0:7]>>[C:3]-[#7:2]-[CH2;D2;+0:1]-[C:4](-[F;D1;H0:5])(-[F;D1;H0:6])-[F;D1;H0:7]
null
[]
0
CELSIUS
1
HOUR
A 2.64 g sample of the compound from step 447a was added dropwise to a suspension of 1.11 g of LAH in ether stirred under N2 at 0° C. After one hour, the reaction was stirred at room temperature for 6 hours. The reaction was quenched by sequential addition of 1.2 mL of water, 1.2 mL of 15% NaOH and 2.4 mL of water. The...
10.6084/m9.figshare.5104873.v1
null
Secondary amide
null
null
null
C1CC[NH]C1.c1ccccc1
Other
CCOCC
0
1
O=C(NC1CCN(Cc2ccccc2)C1)C(F)(F)F>CCOCC>FC(F)(F)CNC1CCN(Cc2ccccc2)C1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-e4fd5c455c0c484e90968bd95fad35ab
CC(C)(C)OC(=O)N(CCF)C1CCN(Cc2ccccc2)C1>>CC(C)(C)OC(=O)N(CCF)C1CCNC1
C(C1=CC=CC=C1)N1CC(CC1)N(CCF)C(=O)OC(C)(C)C.C(=O)[O-].[NH4+]>>C(=O)(OC(C)(C)C)N(CCF)C1CNCC1
c1ccc(C[N:15]2[CH2:14][CH2:13][CH:12]([N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:9][CH2:10][F:11])[CH2:16]2)cc1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]([CH2:9][CH2:10][F:11])[CH:12]1[CH2:13][CH2:14][NH:15][CH2:16]1
CC(C)(C)OC(=O)N(CCF)C1CCN(Cc2ccccc2)C1
CC(C)(C)OC(=O)N(CCF)C1CCNC1
null
[Pd]
null
Deprotection
Hydrogenolysis of tertiary amines
846a35f8c83fa58d2c714915319a8bc96745602a4dd9ac20dbad14bc1e16a470
1c99dd446c0bf4ae872cd8df8de34955be195747c234e9f3c49f46d1de614f66
C1CCNC1
C(-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1)-c1:c:c:c:c:c:1>>[C:4]1-[C:3]-[C:2]-[NH;D2;+0:1]-[C:5]-1
null
[]
null
null
null
null
A 225 mg sample of the compound from step 448a was treated with ammonium formate and 10% Pd/C according to the procedure of step 445b for 1 hour, and the title compound was isolated (190 mg). Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Tertiary amine
Secondary amine
c1ccccc1.C1CC[NH]C1
C1CCNC1
C1CCNC1
Other
[Pd]
null
null
CC(C)(C)OC(=O)N(CCF)C1CCN(Cc2ccccc2)C1>[Pd]>CC(C)(C)OC(=O)N(CCF)C1CCNC1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-7b48bd4f78a1409eb2c2a20f041bf0c4
C=C(C(=O)O)C(F)(F)F.COCN(Cc1ccccc1)C[Si](C)(C)C>>O=C(O)C1(C(F)(F)F)CCN(Cc2ccccc2)C1
FC(C(C(=O)O)=C)(F)F.C(C1=CC=CC=C1)N(COC)C[Si](C)(C)C.FC(C(=O)O)(F)F>>C(C1=CC=CC=C1)N1CC(CC1)(C(=O)O)C(F)(F)F
[O:1]=[C:2]([OH:3])[C:4]([C:5]([F:6])([F:7])[F:8])=[CH2:9].CO[CH2:10][N:11]([CH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1)[CH2:19][Si](C)(C)C>>[O:1]=[C:2]([OH:3])[C:4]1([C:5]([F:6])([F:7])[F:8])[CH2:9][CH2:10][N:11]([CH2:12][c:13]2[cH:14][cH:15][cH:16][cH:17][cH:18]2)[CH2:19]1
C=C(C(=O)O)C(F)(F)F.COCN(Cc1ccccc1)C[Si](C)(C)C
O=C(O)C1(C(F)(F)F)CCN(Cc2ccccc2)C1
null
null
C(Cl)Cl
C-C Coupling
OtherReaction
236b0889f225c4fc56be294ba6ec85e0ad852c9bba072b2a4bee1d1f43481d20
9d56b9958d991884e2b22d7e7d6939373591b095fa4dc9cd59ac7938f5dd12b3
c1ccc(CN2CCCC2)cc1
C-O-[CH2;D2;+0:1]-[#7:2](-[C:3])-[CH2;D2;+0:4]-[Si](-C)(-C)-C.[CH2;D1;+0:5]=[C;H0;D3;+0:6](-[C:7](=[O;D1;H0:8])-[O;D1;H1:9])-[C:10](-[F;D1;H0:11])(-[F;D1;H0:12])-[F;D1;H0:13]>>[C:3]-[#7:2]1-[CH2;D2;+0:1]-[CH2;D2;+0:5]-[C;H0;D4;+0:6](-[C:7](=[O;D1;H0:8])-[O;D1;H1:9])(-[C:10](-[F;D1;H0:11])(-[F;D1;H0:12])-[F;D1;H0:13])-[...
null
[]
null
null
2
HOUR
A 2.48 g sample of 2-(trifluoromethyl)acrylic acid was dissolved in 40 mL of dry methylene chloride, and a solution of 4.75 g of N-benzyl-N-(methoxymethyl)-trimethylsilylmethylamine in 20 mL of dry methylene chloride was added dropwise under N2 at 0° C. To this mixture was added 2 mL of trifluoroacetic acid, and the mi...
10.6084/m9.figshare.5104873.v1
null
Ether.Vinyl.Silyl protective group
null
null
C1CC[NH]C1
C1CC[NH]C1.c1ccccc1
HO-
C(Cl)Cl
null
2
C=C(C(=O)O)C(F)(F)F.COCN(Cc1ccccc1)C[Si](C)(C)C>C(Cl)Cl>O=C(O)C1(C(F)(F)F)CCN(Cc2ccccc2)C1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-3c14aa7c3cf94af8afc09046f03b475b
CC(C)(C)O.O=C(O)C1(C(F)(F)F)CCN(Cc2ccccc2)C1.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>>CC(C)(C)OC(=O)NC1(C(F)(F)F)CCN(Cc2ccccc2)C1
C(C1=CC=CC=C1)N1CC(CC1)(C(=O)O)C(F)(F)F.C1(=CC=CC=C1)P(=O)(C1=CC=CC=C1)N=[N+]=[N-].CN(C)C.C(C)(C)(C)O>>C(C1=CC=CC=C1)N1CC(CC1)(C(F)(F)F)NC(=O)OC(C)(C)C
[CH3:1][C:2]([CH3:3])([CH3:4])[OH:5].O[C:6](=[O:7])[C:9]1([C:10]([F:11])([F:12])[F:13])[CH2:14][CH2:15][N:16]([CH2:17][c:18]2[cH:19][cH:20][cH:21][cH:22][cH:23]2)[CH2:24]1.[N-]=[N+]=[N:8]P(=O)(c1ccccc1)c1ccccc1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][C:9]1([C:10]([F:11])([F:12])[F:13])[CH2:14][CH2:15][N...
CC(C)(C)O.O=C(O)C1(C(F)(F)F)CCN(Cc2ccccc2)C1.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
CC(C)(C)OC(=O)NC1(C(F)(F)F)CCN(Cc2ccccc2)C1
null
null
null
Protection
OtherReaction
1baf304561413bd40a0af5d9e8984f017d308e72c1984fccd5cfccfb8e775719
b944663b5278c281edc6c72611c69e4309c3f5728dcd63d51413085e18c1d2e7
c1ccc(CN2CCCC2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D4;+0:3]1(-[C:4](-[F;D1;H0:5])(-[F;D1;H0:6])-[F;D1;H0:7])-[C:8]-[C:9]-[#7:10](-[C:11])-[C:12]-1.O=P(-[N;H0;D2;+0:13]=[N+]=[N-])(-c1:c:c:c:c:c:1)-c1:c:c:c:c:c:1.[C;D1;H3:14]-[C:15](-[C;D1;H3:16])(-[C;D1;H3:17])-[OH;D1;+0:18]>>[C:11]-[#7:10]1-[C:9]-[C:8]-[C;H0;D4;+0:3](-[NH;D2;+0:13]-...
96.7
[{"value": 96.7, "product": "C(C1=CC=CC=C1)N1CC(CC1)(C(F)(F)F)NC(=O)OC(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 1.42 g of the compound from step 454a, 1.71 g of diphenylphosphoryl azide, 12.3 g of t-butanol and 0.627 g of trimethyl amine was heated at reflux under N2 for 24 hours. The mixture was concentrated to dryness, and the residue was dissolved in methylene chloride. The solution was washed with satd. NaHCO3 a...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Azide.Tertiary alcohol
Carbamic ester.Ether.Boc
C1CC[NH]C1.c1ccccc1.c1ccccc1
C1CC[NH]C1
C1CC[NH]C1.c1ccccc1
HO-
null
null
null
CC(C)(C)O.O=C(O)C1(C(F)(F)F)CCN(Cc2ccccc2)C1.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>>CC(C)(C)OC(=O)NC1(C(F)(F)F)CCN(Cc2ccccc2)C1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-593685df77934601a60a768a24ebbaa0
C=C(C(=O)O)C(F)(F)F.COCN(Cc1ccccc1)C[Si](C)(C)C>>O=C(O)C1(C(F)(F)F)CCN(Cc2ccccc2)C1
FC(C(C(=O)O)=C)(F)F.C(C1=CC=CC=C1)N(COC)C[Si](C)(C)C.C(=O)(C(F)(F)F)O>>C(C1=CC=CC=C1)N1CC(CC1)(C(=O)O)C(F)(F)F
[O:1]=[C:2]([OH:3])[C:4]([C:5]([F:6])([F:7])[F:8])=[CH2:9].CO[CH2:10][N:11]([CH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1)[CH2:19][Si](C)(C)C>>[O:1]=[C:2]([OH:3])[C:4]1([C:5]([F:6])([F:7])[F:8])[CH2:9][CH2:10][N:11]([CH2:12][c:13]2[cH:14][cH:15][cH:16][cH:17][cH:18]2)[CH2:19]1
C=C(C(=O)O)C(F)(F)F.COCN(Cc1ccccc1)C[Si](C)(C)C
O=C(O)C1(C(F)(F)F)CCN(Cc2ccccc2)C1
null
null
C(Cl)Cl
C-C Coupling
OtherReaction
236b0889f225c4fc56be294ba6ec85e0ad852c9bba072b2a4bee1d1f43481d20
9d56b9958d991884e2b22d7e7d6939373591b095fa4dc9cd59ac7938f5dd12b3
c1ccc(CN2CCCC2)cc1
C-O-[CH2;D2;+0:1]-[#7:2](-[C:3])-[CH2;D2;+0:4]-[Si](-C)(-C)-C.[CH2;D1;+0:5]=[C;H0;D3;+0:6](-[C:7](=[O;D1;H0:8])-[O;D1;H1:9])-[C:10](-[F;D1;H0:11])(-[F;D1;H0:12])-[F;D1;H0:13]>>[C:3]-[#7:2]1-[CH2;D2;+0:1]-[CH2;D2;+0:5]-[C;H0;D4;+0:6](-[C:7](=[O;D1;H0:8])-[O;D1;H1:9])(-[C:10](-[F;D1;H0:11])(-[F;D1;H0:12])-[F;D1;H0:13])-[...
58.9
[{"value": 58.9, "product": "C(C1=CC=CC=C1)N1CC(CC1)(C(=O)O)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
2-(Trifluoromethyl)acrylic acid (2.48 g, 20 mmol) was dissolved in 30 mL of dry methylene chloride, a solution of 4.75 g (20 mmol) of N-benzyl-N-(methoxymethyl)-trimethylsilylmethylamine in 20 mL of dry methylene chloride was added dropwise under N2 at 0° C. To this solution was added 2 mL of TFA, and the solution was ...
10.6084/m9.figshare.5104873.v1
null
Ether.Vinyl.Silyl protective group
null
null
C1CC[NH]C1
C1CC[NH]C1.c1ccccc1
HO-
C(Cl)Cl
null
2
C=C(C(=O)O)C(F)(F)F.COCN(Cc1ccccc1)C[Si](C)(C)C>C(Cl)Cl>O=C(O)C1(C(F)(F)F)CCN(Cc2ccccc2)C1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-2fa90453573642919084e8719e36a12a
O=C(O)C1(C(F)(F)F)CCN(Cc2ccccc2)C1>>OCC1(C(F)(F)F)CCN(Cc2ccccc2)C1
C(C1=CC=CC=C1)N1CC(CC1)(C(=O)O)C(F)(F)F.[H-].[H-].[H-].[H-].[Li+].[Al+3]>>C(C1=CC=CC=C1)N1CC(CC1)(CO)C(F)(F)F
O=[C:2]([OH:1])[C:3]1([C:4]([F:5])([F:6])[F:7])[CH2:8][CH2:9][N:10]([CH2:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[CH2:18]1>>[OH:1][CH2:2][C:3]1([C:4]([F:5])([F:6])[F:7])[CH2:8][CH2:9][N:10]([CH2:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[CH2:18]1
O=C(O)C1(C(F)(F)F)CCN(Cc2ccccc2)C1
OCC1(C(F)(F)F)CCN(Cc2ccccc2)C1
null
null
C1CCOC1
Reduction
Reduction of carboxylic acid to primary alcohol
0db83a5ebe1e318b78b55461cf7eb8f7c004eef0f9e3b6666d3df4c96b5f665e
93b4621647b04d2ad2f2825215b1567f171ba61fe10d136b5db6ea0470aa4932
c1ccc(CN2CCCC2)cc1
O=[C;H0;D3;+0:1](-[O;D1;H1:2])-[C:3](-[C:4](-[F;D1;H0:5])(-[F;D1;H0:6])-[F;D1;H0:7])(-[C:8])-[C:9]-[#7:10]>>[#7:10]-[C:9]-[C:3](-[CH2;D2;+0:1]-[O;D1;H1:2])(-[C:4](-[F;D1;H0:5])(-[F;D1;H0:6])-[F;D1;H0:7])-[C:8]
99.9
[{"value": 99.9, "product": "C(C1=CC=CC=C1)N1CC(CC1)(CO)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
The compound from step 456a (2.32 g) was dissolved in 60 mL of dry THF, 1.12 eq of LAH (1N in dry THF) was added, and the reaction was stirred under N2 for 3 hours. The reaction was quenched by the sequential dropwise addition of 0.35 mL water, 0.35 mL of 15% NaOH and 1.3 mL of water, then the mixture was stirred for 1...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary alcohol
null
null
C1CC[NH]C1.c1ccccc1
Other
C1CCOC1
null
3
O=C(O)C1(C(F)(F)F)CCN(Cc2ccccc2)C1>C1CCOC1>OCC1(C(F)(F)F)CCN(Cc2ccccc2)C1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-e94dfad47a4a48328c7cf02bef7e5975
Cc1ccc(S(=O)(=O)Cl)cc1.OCC1(C(F)(F)F)CCN(Cc2ccccc2)C1>>Cc1ccccc1S(=O)(=O)OCC1(C(F)(F)F)CCN(Cc2ccccc2)C1
C(C1=CC=CC=C1)N1CC(CC1)(CO)C(F)(F)F.N1=CC=CC=C1.C1(=CC=C(C=C1)S(=O)(=O)Cl)C.N1=CC=CC=C1>>C(C1=CC=CC=C1)N1CC(CC1)(COS(=O)(=O)C=1C(=CC=CC1)C)C(F)(F)F
Cl[S:8]([c:7]1[cH:4][cH:3][c:2]([CH3:1])[cH:5][cH:6]1)(=[O:9])=[O:10].[OH:11][CH2:12][C:13]1([C:14]([F:15])([F:16])[F:17])[CH2:18][CH2:19][N:20]([CH2:21][c:22]2[cH:23][cH:24][cH:25][cH:26][cH:27]2)[CH2:28]1>>[CH3:1][c:2]1[cH:3][cH:4][cH:5][cH:6][c:7]1[S:8](=[O:9])(=[O:10])[O:11][CH2:12][C:13]1([C:14]([F:15])([F:16])[F:...
Cc1ccc(S(=O)(=O)Cl)cc1.OCC1(C(F)(F)F)CCN(Cc2ccccc2)C1
Cc1ccccc1S(=O)(=O)OCC1(C(F)(F)F)CCN(Cc2ccccc2)C1
null
null
C(Cl)Cl
Acylation
OtherReaction
05fa5c39bec607db4d2ecbdc0d03c290b9a310bbf0fb1c4f6cab56ff403f2979
cac1a51abad701d3f26583520679a70ff72a7c9f3ad49ba72aafddf242cb8589
O=S(=O)(OCC1CCN(Cc2ccccc2)C1)c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c;H0;D3;+0:4]1:[c:5]:[cH;D2;+0:6]:[c;H0;D3;+0:7](-[C;D1;H3:8]):[c:9]:[cH;D2;+0:10]:1.[C:11]-[C:12]-[OH;D1;+0:13]>>[C:11]-[C:12]-[O;H0;D2;+0:13]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c;H0;D3;+0:4]1:[c:5]:[cH;D2;+0:6]:[cH;D2;+0:10]:[c:9]:[c;H0;D3;+0:7]:1-[C;D1;H3:8]
null
[]
0
CELSIUS
null
null
The compound from step 456b (1.61 g) was dissolved in dry pyridine, and the solution was cooled to 0° C. To this was added 1.458 g of p-toluenesulfonyl chloride in 4 mL of dry pyridine, and the reaction was stirred at 0.C for 4 days. The mixture was diluted with 300 mL of methylene chloride, then washed with water and ...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Primary alcohol.Sulfonyl halide
Sulfonate
c1ccccc1
c1ccccc1
c1ccccc1.C1CC[NH]C1.c1ccccc1
HCl
C(Cl)Cl
0
null
Cc1ccc(S(=O)(=O)Cl)cc1.OCC1(C(F)(F)F)CCN(Cc2ccccc2)C1>C(Cl)Cl>Cc1ccccc1S(=O)(=O)OCC1(C(F)(F)F)CCN(Cc2ccccc2)C1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-a4ea40c7f75d4214b8389b24edce6e3b
CCOC(=O)C1CN(Cc2ccccc2)CC1C(=O)OCC.N>>O=C1CC2CN(Cc3ccccc3)CC2C(=O)N1
[Cl-].[NH4+].C(C)OC(=O)C1CN(CC1C(=O)OCC)CC1=CC=CC=C1.C1CCOC1.N>>C(C1=CC=CC=C1)N1CC2C(NC(CC2C1)=O)=O
CCO[C:3](=[O:1])[CH:4]1[CH2:5][N:6]([CH2:7][c:8]2[cH:9][cH:10][cH:11][cH:12][cH:13]2)[CH2:14][CH:15]1[C:16](OCC)=[O:17].[NH3:18]>>[O:1]=[C:2]1[CH2:3][CH:4]2[CH2:5][N:6]([CH2:7][c:8]3[cH:9][cH:10][cH:11][cH:12][cH:13]3)[CH2:14][CH:15]2[C:16](=[O:17])[NH:18]1
CCOC(=O)C1CN(Cc2ccccc2)CC1C(=O)OCC.N
O=C1CC2CN(Cc3ccccc3)CC2C(=O)N1
null
null
null
Acylation
OtherReaction
040b55450bf31cac5dd8c67e6fe10643f123c9e4d81d04727113c7719ce7596b
ddd529cd6613435ea56b03afd8160ee4423a1103a480d9c38d135c487ceb3c06
O=C1CC2CN(Cc3ccccc3)CC2C(=O)N1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[#7:5]-[C:6]-[C:7]-1-[C;H0;D3;+0:8](=[O;H0;D1;+0:9])-O-C-C.[NH3;D0;+0:10]>>[O;D1;H0:2]=[C;H0;D3;+0:1]1-[NH;D2;+0:10]-[C:11](=[O;H0;D1;+0:9])-[CH2;D2;+0:8]-[C:7]2-[C:6]-[#7:5]-[C:4]-[C:3]-2-1
null
[]
-40
CELSIUS
null
null
A solution of 9.00 mmol of Na in liquid NH3 was prepared at -78° C. To this was added 15 mg of FeCl3, and the reaction mixture was warmed to -40° C. To this solution, stirred under N2, a cooled (-40° C.) solution of the compound (957 mg) from step 457a in THF was added over a 10 minute period, and the reaction mixture ...
10.6084/m9.figshare.5104873.v1
null
Ester.Ester
Unsubstituted dicarboximide
null
C1CC2C[NH]CC2CN1
C1CC2C[NH]CC2CN1.c1ccccc1
HO-
null
-40
null
CCOC(=O)C1CN(Cc2ccccc2)CC1C(=O)OCC.N>>O=C1CC2CN(Cc3ccccc3)CC2C(=O)N1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-eb07eb00507a464db46f471df4d8364d
BrCc1ccccc1.O=C1CC2CN(Cc3ccccc3)CC2C(=O)N1>>O=C1CC2CN(Cc3ccccc3)CC2C(=O)N1Cc1ccccc1
C(=O)([O-])[O-].[K+].[K+].C(C1=CC=CC=C1)N1CC2C(NC(CC2C1)=O)=O.C(C1=CC=CC=C1)Br>>C(C1=CC=CC=C1)N1CC2C(N(C(CC2C1)=O)CC1=CC=CC=C1)=O
Br[CH2:19][c:20]1[cH:21][cH:22][cH:23][cH:24][cH:25]1.[O:1]=[C:2]1[CH2:3][CH:4]2[CH2:5][N:6]([CH2:7][c:8]3[cH:9][cH:10][cH:11][cH:12][cH:13]3)[CH2:14][CH:15]2[C:16](=[O:17])[NH:18]1>>[O:1]=[C:2]1[CH2:3][CH:4]2[CH2:5][N:6]([CH2:7][c:8]3[cH:9][cH:10][cH:11][cH:12][cH:13]3)[CH2:14][CH:15]2[C:16](=[O:17])[N:18]1[CH2:19][c:...
BrCc1ccccc1.O=C1CC2CN(Cc3ccccc3)CC2C(=O)N1
O=C1CC2CN(Cc3ccccc3)CC2C(=O)N1Cc1ccccc1
null
null
CN(C)C=O.C(C)(=O)OCC
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
0594d38779d714bd65d325cc095c7894514d8dcb6fbbf3a456b8ee9ec8e0de46
ed5b40ca5c14bda1cdc43d7e7526ae39e9e787b52b58ca2afd56239c19d62539
O=C1CC2CN(Cc3ccccc3)CC2C(=O)N1Cc1ccccc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[C:5]-[C:6](=[O;D1;H0:7])-[NH;D2;+0:8]-[C:9](=[O;D1;H0:10])-[C:11]>>[C:5]-[C:6](=[O;D1;H0:7])-[N;H0;D3;+0:8](-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4])-[C:9](=[O;D1;H0:10])-[C:11]
111.4
[{"value": 111.4, "product": "C(C1=CC=CC=C1)N1CC2C(N(C(CC2C1)=O)CC1=CC=CC=C1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
6.5
HOUR
To a mixture of 905 mg of K2CO3 and 400 mg of the compound from step 457b in 5 mL of DMF was added 308 mg of benzyl bromide, and the reaction mixture was stirred at room temperature under N2 for 6.5 hours. The mixture was diluted with ethyl acetate, which was washed with water and brine, dried and concentrated to give ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Unsubstituted dicarboximide
Substituted dicarboximide
C1CC2C[NH]CC2CN1
C1CC2C[NH]CC2C[NH]1
C1CC2C[NH]CC2C[NH]1.c1ccccc1.c1ccccc1
HBr
CN(C)C=O.C(C)(=O)OCC
null
6.5
BrCc1ccccc1.O=C1CC2CN(Cc3ccccc3)CC2C(=O)N1>CN(C)C=O.C(C)(=O)OCC>O=C1CC2CN(Cc3ccccc3)CC2C(=O)N1Cc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-88b5cc36e3014d199d30d93dc27d1375
O=C1CC2CNCC2C(=O)N1Cc1ccccc1>>c1ccc(CN2CCC3CNCC3C2)cc1
[H-].[H-].[H-].[H-].[Li+].[Al+3].C(C1=CC=CC=C1)N1C(C2C(CC1=O)CNC2)=O>>C(C1=CC=CC=C1)N1CC2C(CC1)CNC2
O=[C:7]1[N:6]([CH2:5][c:4]2[cH:3][cH:2][cH:1][cH:16][cH:15]2)[C:14](=O)[CH:13]2[CH:9]([CH2:8]1)[CH2:10][NH:11][CH2:12]2>>[cH:1]1[cH:2][cH:3][c:4]([CH2:5][N:6]2[CH2:7][CH2:8][CH:9]3[CH2:10][NH:11][CH2:12][CH:13]3[CH2:14]2)[cH:15][cH:16]1
O=C1CC2CNCC2C(=O)N1Cc1ccccc1
c1ccc(CN2CCC3CNCC3C2)cc1
null
null
CCOCC.C(Cl)Cl
Reduction
OtherReaction
51bf16baee6b2913e4f7b53e52cb314a9dfb39221c7bf5f3f490de44e84bc2de
5c48d2345eb2fa995a1eb3dce1782e140f14b5faddfaad3c600fc635c2b998a2
c1ccc(CN2CCC3CNCC3C2)cc1
O=[C;H0;D3;+0:1]1-[#7:2](-[C:3])-[C;H0;D3;+0:4](=O)-[C:5]-[C:6]-[C:7]-1-[C:8]-[#7:9]>>[#7:9]-[C:8]-[C:7]1-[C:6]-[C:5]-[CH2;D2;+0:4]-[#7:2](-[C:3])-[CH2;D2;+0:1]-1
81.4
[{"value": 81.4, "product": "C(C1=CC=CC=C1)N1CC2C(CC1)CNC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
10
CELSIUS
null
null
A suspension of 266 mg of LAH in 10 mL of ether was stirred at 10° C. under N2. To this suspension was added 540 mg of the compound from step 457d dissolved in 10 mL of methylene chloride. The mixture was stirred under N2 for 1.5 hours. The reaction was quenched by the sequential dropwise addition of 0.3 mL water, 0.3 ...
10.6084/m9.figshare.5104873.v1
null
Substituted dicarboximide
null
C1CC2CNCC2C[NH]1
C1CC2CNCC2C[NH]1
c1ccccc1.C1CC2CNCC2C[NH]1
Other
CCOCC.C(Cl)Cl
10
null
O=C1CC2CNCC2C(=O)N1Cc1ccccc1>CCOCC.C(Cl)Cl>c1ccc(CN2CCC3CNCC3C2)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-fab91be0255847869bf52f34533aab78
O=C(C1CC1)C1CCN(Cc2ccccc2)C1.[NH4+]>>NC(C1CC1)C1CCN(Cc2ccccc2)C1
C(C1=CC=CC=C1)N1CC(CC1)C(=O)C1CC1.C(C)(=O)[O-].[NH4+].[BH3-]C#N.[Na+]>>C(C1=CC=CC=C1)N1CC(CC1)C(C1CC1)N
O=[C:2]([CH:3]1[CH2:4][CH2:5]1)[CH:6]1[CH2:7][CH2:8][N:9]([CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:15][cH:16]2)[CH2:17]1.[NH4+:1]>>[NH2:1][CH:2]([CH:3]1[CH2:4][CH2:5]1)[CH:6]1[CH2:7][CH2:8][N:9]([CH2:10][c:11]2[cH:12][cH:13][cH:14][cH:15][cH:16]2)[CH2:17]1
O=C(C1CC1)C1CCN(Cc2ccccc2)C1.[NH4+]
NC(C1CC1)C1CCN(Cc2ccccc2)C1
null
null
CO
Functional Group Interconversion
OtherReaction
14af499c4b742b1ab2135a986a4f7f4e6dda0ad50987736be8cf00d531c63192
2ef9e3e9915394571ec6196ff6ea06bca9f3dff8c6f6f43c81edc876014a94a5
c1ccc(CN2CCC(CC3CC3)C2)cc1
O=[C;H0;D3;+0:1](-[C:2]1-[C:3]-[C:4]-1)-[C:5](-[C:6])-[C:7]-[#7:8].[NH4+;D0:9]>>[#7:8]-[C:7]-[C:5](-[CH;D3;+0:1](-[NH2;D1;+0:9])-[C:2]1-[C:3]-[C:4]-1)-[C:6]
null
[]
null
null
16
HOUR
A 1 g sample of the compound from step 470b, 3.37 g of ammonium acetate and 274 mg of NaBH3CN were dissolved in 15 mL of methanol, 1.2 g of 4 Å molecular sieves were added, and the mixture was stirred at room temperature under N2 for 16 hours. The mixture was filtered, the sieves washed with methanol, the wash and filt...
10.6084/m9.figshare.5104873.v1
null
Ketone
Primary amine
null
null
C1CC1.C1CC[NH]C1.c1ccccc1
HO-
CO
null
16
O=C(C1CC1)C1CCN(Cc2ccccc2)C1.[NH4+]>CO>NC(C1CC1)C1CCN(Cc2ccccc2)C1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-599ef965de604788a8f4493886ac4c46
CC(C)(C)OC(=O)NC(C1CC1)C1CCN(Cc2ccccc2)C1>>CC(C)(C)OC(=O)NC(C1CC1)C1CCNC1
C(=O)(OC(C)(C)C)NC(C1CC1)C1CN(CC1)CC1=CC=CC=C1>>C(=O)(OC(C)(C)C)NC(C1CC1)C1CNCC1
c1ccc(C[N:16]2[CH2:15][CH2:14][CH:13]([CH:9]([NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH:10]3[CH2:11][CH2:12]3)[CH2:17]2)cc1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][CH:9]([CH:10]1[CH2:11][CH2:12]1)[CH:13]1[CH2:14][CH2:15][NH:16][CH2:17]1
CC(C)(C)OC(=O)NC(C1CC1)C1CCN(Cc2ccccc2)C1
CC(C)(C)OC(=O)NC(C1CC1)C1CCNC1
null
[Pd]
CO
Deprotection
Hydrogenolysis of tertiary amines
846a35f8c83fa58d2c714915319a8bc96745602a4dd9ac20dbad14bc1e16a470
1c99dd446c0bf4ae872cd8df8de34955be195747c234e9f3c49f46d1de614f66
C1CC(CC2CC2)CN1
C(-[N;H0;D3;+0:1]1-[C:2]-[C:3]-[C:4]-[C:5]-1)-c1:c:c:c:c:c:1>>[C:4]1-[C:3]-[C:2]-[NH;D2;+0:1]-[C:5]-1
35.1
[{"value": 35.1, "product": "C(=O)(OC(C)(C)C)NC(C1CC1)C1CNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
42
HOUR
A sample (548 mg) of the compound from step 470d was dissolved in methanol, 140 mg of 10% Pd/C was added, and the mixture was hydrogenated at 4 atm H2 for 42 hours at room temperature. The solution was filtered, and the solvent was removed to give 140 mg of the title compound. Conditions: See reaction.notes.procedure_d...
10.6084/m9.figshare.5104873.v1
null
Tertiary amine
Secondary amine
c1ccccc1.C1CC[NH]C1
C1CCNC1
C1CC1.C1CCNC1
Other
[Pd].CO
null
42
CC(C)(C)OC(=O)NC(C1CC1)C1CCN(Cc2ccccc2)C1>[Pd].CO>CC(C)(C)OC(=O)NC(C1CC1)C1CCNC1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-bd232c0b8b38439bb9e8a89504c75742
CCOC(=O)C[C@H](C[N+](=O)[O-])[C@@H]1CCCN1C(=O)OC(C)(C)C>>CC(C)(C)OC(=O)N1CCC[C@H]1[C@H](CCO)C[N+](=O)[O-]
C(=O)(OC(C)(C)C)N1[C@@H](CCC1)[C@H](CC(=O)OCC)C[N+](=O)[O-].[H-].[H-].[H-].[H-].[Li+].[Al+3]>>C(=O)(OC(C)(C)C)N1[C@@H](CCC1)[C@H](CCO)C[N+](=O)[O-]
CCO[C:15]([CH2:14][C@@H:13]([C@H:12]1[N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:9][CH2:10][CH2:11]1)[CH2:17][N+:18](=[O:19])[O-:20])=[O:16]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH2:11][C@H:12]1[C@H:13]([CH2:14][CH2:15][OH:16])[CH2:17][N+:18](=[O:19])[O-:20]
CCOC(=O)C[C@H](C[N+](=O)[O-])[C@@H]1CCCN1C(=O)OC(C)(C)C
CC(C)(C)OC(=O)N1CCC[C@H]1[C@H](CCO)C[N+](=O)[O-]
null
null
CCOCC
Reduction
Reduction of ester to primary alcohol
21d61543c6ec8a8cebe1b3ef55ef3dd20acbf79a4f1c12a7fb51e32be7a3248a
1fbcd628a0426673c5d10aa49a977cd2d1ae02a8cdf57bbb10d94aa03a94e937
C1CCNC1
C-C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[C:3]-[C:4]>>[C:4]-[C:3]-[CH2;D2;+0:1]-[OH;D1;+0:2]
null
[]
null
null
null
null
A 7.5 g sample of ethyl 3-(R)-(1-BOC-2-(S)-pyrrolidinyl)-4-nitrobutanoate (prepared according to the procedure of Hayakawa et al., U.S. Pat. No. 5,098,912, issued Mar. 24, 1992) was dissolved in 35 mL of ether and treated with 0.76 g of LAH. After careful quenching of the excess reagents, the title compound was extract...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary alcohol
null
null
C1CC[NH]C1
HO-
CCOCC
null
null
CCOC(=O)C[C@H](C[N+](=O)[O-])[C@@H]1CCCN1C(=O)OC(C)(C)C>CCOCC>CC(C)(C)OC(=O)N1CCC[C@H]1[C@H](CCO)C[N+](=O)[O-]
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-d35336a8d63f46faa12cbe3c8194e4f3
CC(C)(C)OC(=O)N1CCC[C@H]1[C@H](CCO)C[N+](=O)[O-].CS(=O)(=O)Cl>>CC(C)(C)OC(=O)N1CCC[C@H]1[C@H](CCOS(C)(=O)=O)C[N+](=O)[O-]
C(=O)(OC(C)(C)C)N1[C@@H](CCC1)[C@H](CCO)C[N+](=O)[O-].CS(=O)(=O)Cl>>CS(=O)(=O)OCC[C@H](C[N+](=O)[O-])[C@H]1N(CCC1)C(=O)OC(C)(C)C
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH2:11][C@H:12]1[C@H:13]([CH2:14][CH2:15][OH:16])[CH2:21][N+:22](=[O:23])[O-:24].Cl[S:17]([CH3:18])(=[O:19])=[O:20]>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH2:11][C@H:12]1[C@H:13]([CH2:14][CH2:15][O:16][S:17]([CH3:18])...
CC(C)(C)OC(=O)N1CCC[C@H]1[C@H](CCO)C[N+](=O)[O-].CS(=O)(=O)Cl
CC(C)(C)OC(=O)N1CCC[C@H]1[C@H](CCOS(C)(=O)=O)C[N+](=O)[O-]
null
null
C(Cl)Cl
Acylation
Formation of Sulfonic Esters
2fa969eb2c954bb96793348a1b2335ec63fbd290dadec6e3e02295e1768e64cf
cb77b899e4adf980b1def97230ef2861660fd7f9602260ec64747d9afd3a795a
C1CCNC1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[C:5]-[C:6]-[OH;D1;+0:7]>>[C:5]-[C:6]-[O;H0;D2;+0:7]-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4]
null
[]
null
null
null
null
A 3.5 g sample of the alcohol from step 471a above was dissolved in 25 mL of methylene chloride and treated with methanesulfonyl chloride an TEA at 0° C. for 2 hours. The reaction mixture was washed with NaHCO3 solution and water, and the solvent was removed. The residue was chromatographed on silica gel to give 3 g of...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Sulfonyl halide
Mesylate
null
null
C1CC[NH]C1
HCl
C(Cl)Cl
null
null
CC(C)(C)OC(=O)N1CCC[C@H]1[C@H](CCO)C[N+](=O)[O-].CS(=O)(=O)Cl>C(Cl)Cl>CC(C)(C)OC(=O)N1CCC[C@H]1[C@H](CCOS(C)(=O)=O)C[N+](=O)[O-]
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-722fc1c8e1ff43a08b3a226da745e8d4
CC(C)(C)OC(=O)N1CCC[C@H]1[C@H](CCO)C[N+](=O)[O-]>>CC(C)(C)OC(=O)N1CCC[C@H]1[C@@H]1CCNC1
C(=O)(OC(C)(C)C)N1[C@@H](CCC1)[C@H](CCO)C[N+](=O)[O-]>>C(=O)(OC(C)(C)C)N1[C@@H](CCC1)[C@H]1CNCC1
O=[N+:16]([O-])[CH2:17][C@H:13]([C@H:12]1[N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:9][CH2:10][CH2:11]1)[CH2:14][CH2:15]O>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]1[CH2:9][CH2:10][CH2:11][C@H:12]1[C@@H:13]1[CH2:14][CH2:15][NH:16][CH2:17]1
CC(C)(C)OC(=O)N1CCC[C@H]1[C@H](CCO)C[N+](=O)[O-]
CC(C)(C)OC(=O)N1CCC[C@H]1[C@@H]1CCNC1
null
[Pd]
CO
Functional Group Interconversion
OtherReaction
48828c3c93909116a9ae11bcb1915303abfc7a49ed11087299d13a2c0f45df78
764b36840e9259f724a61c40582ce8fb4279526cbcc6fde89825049b30b4f9a4
C1CN[C@H]([C@@H]2CCNC2)C1
O-[CH2;D2;+0:1]-[C:2]-[C:3]-[C:4]-[N+;H0;D3:5](=O)-[O-]>>[C:3]1-[C:2]-[CH2;D2;+0:1]-[NH;D2;+0:5]-[C:4]-1
null
[]
null
null
null
null
The ether compound from step 471a was treated by hydrogenation at 4 atm H2 over Pd/C in methanol to give the tile compound. Conditions: See reaction.notes.procedure_details. Workup: to give the tile compound
10.6084/m9.figshare.5104873.v1
null
Nitro group.Primary alcohol
Secondary amine
null
C1CCNC1
C1CC[NH]C1.C1CCNC1
Other
[Pd].CO
null
null
CC(C)(C)OC(=O)N1CCC[C@H]1[C@H](CCO)C[N+](=O)[O-]>[Pd].CO>CC(C)(C)OC(=O)N1CCC[C@H]1[C@@H]1CCNC1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-bb91f751bb204267a4e371b6462d78b9
CC(C)(C)OC(=O)CC(=O)OC(C)(C)C.CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O>>CCOC(=O)c1cc(C2CC2)c2c(C)c(CC(=O)OC(c3ccccc3)c3ccccc3)c(F)cn2c1=O
O.C(CC(=O)OC(C)(C)C)(=O)OC(C)(C)C.[H-].[Na+].C(C)OC(=O)C1=CC(=C2C(=C(C(=CN2C1=O)F)Cl)C)C1CC1>>C(C)OC(=O)C1=CC(=C2C(=C(C(=CN2C1=O)F)CC(=O)OC(C1=CC=CC=C1)C1=CC=CC=C1)C)C1CC1
O=[C:24](O[C:26]([CH3:21])([CH3:22])[CH3:25])[CH2:16][C:17](=[O:18])[O:19][C:20]([CH3:23])([CH3:27])[CH3:31].Cl[c:15]1[c:13]([CH3:14])[c:12]2[c:8]([CH:9]3[CH2:10][CH2:11]3)[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:37](=[O:38])[n:36]2[cH:35][c:33]1[F:34]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]([CH:9]2[C...
CC(C)(C)OC(=O)CC(=O)OC(C)(C)C.CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O
CCOC(=O)c1cc(C2CC2)c2c(C)c(CC(=O)OC(c3ccccc3)c3ccccc3)c(F)cn2c1=O
null
null
CN(C)C=O
C-C Coupling
OtherReaction
2f864c10139aa052df1f1d82796d030c15fc9d3baed31fefa0f2c376331a7931
308879df3a0fd871e75ae976291abb2a3f6f52c3704a24fb5ddea62844558dfc
O=C(Cc1ccn2c(=O)ccc(C3CC3)c2c1)OC(c1ccccc1)c1ccccc1
Cl-[c;H0;D3;+0:1]1:[c:2](-[C;D1;H3:3]):[c:4](:[c:5]):[#7;a:6](:[c:7]):[c:8]:[c:9]:1-[F;D1;H0:10].O=[C;H0;D3;+0:11](-O-[C;H0;D4;+0:12](-[CH3;D1;+0:13])(-[CH3;D1;+0:14])-[CH3;D1;+0:15])-[CH2;D2;+0:16]-[C:17](=[O;D1;H0:18])-[#8:19]-[C;H0;D4;+0:20](-[CH3;D1;+0:21])(-[CH3;D1;+0:22])-[CH3;D1;+0:23]>>[C;D1;H3:3]-[c:2]1:[c:4](...
null
[]
null
null
null
null
To a suspension of NaH in DMF with ice bath cooling is added di-t-butyl malonate. After the addition, 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester from Example 253i above is added. The reaction is then heated to 50° to 60° C., and the mixture is poured into water and acidi...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ester.Ester.Boc.Boc
Ester
c1ccn2ccccc2c1
c1ccn2ccccc2c1.c1ccccc1.c1ccccc1
C1CC1.c1ccn2ccccc2c1.c1ccccc1.c1ccccc1
HCl
CN(C)C=O
null
null
CC(C)(C)OC(=O)CC(=O)OC(C)(C)C.CCOC(=O)c1cc(C2CC2)c2c(C)c(Cl)c(F)cn2c1=O>CN(C)C=O>CCOC(=O)c1cc(C2CC2)c2c(C)c(CC(=O)OC(c3ccccc3)c3ccccc3)c(F)cn2c1=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-e9a35b5778f84e018ef46a7daf51dbfd
CC(C)(C)O.CCOC(=O)c1cc(C2CC2)c2c(C)c(C3(C(=O)O)CC3)c(F)cn2c1=O.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>>CCOC(=O)c1cc(C2CC2)c2c(C)c(C3(NC(=O)OC(C)(C)C)CC3)c(F)cn2c1=O
C(C)OC(=O)C1=CC(=C2C(=C(C(=CN2C1=O)F)C1(CC1)C(=O)O)C)C1CC1.C1(=CC=CC=C1)P(=O)(C1=CC=CC=C1)N=[N+]=[N-].C(C)(C)(C)O.C(C)N(CC)CC>>C(C)OC(=O)C1=CC(=C2C(=C(C(=CN2C1=O)F)C1(CC1)NC(=O)OC(C)(C)C)C)C1CC1
[OH:20][C:21]([CH3:22])([CH3:23])[CH3:24].O[C:18]([C:16]1([c:15]2[c:13]([CH3:14])[c:12]3[c:8]([CH:9]4[CH2:10][CH2:11]4)[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:31](=[O:32])[n:30]3[cH:29][c:27]2[F:28])[CH2:25][CH2:26]1)=[O:19].[N-]=[N+]=[N:17]P(=O)(c1ccccc1)c1ccccc1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c...
CC(C)(C)O.CCOC(=O)c1cc(C2CC2)c2c(C)c(C3(C(=O)O)CC3)c(F)cn2c1=O.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
CCOC(=O)c1cc(C2CC2)c2c(C)c(C3(NC(=O)OC(C)(C)C)CC3)c(F)cn2c1=O
null
null
O1CCOCC1
Protection
OtherReaction
14cfb34213c56f76d6c0b0fbad6fbcbdb23f6c7be623f3f9740afd7d91c67e5f
b944663b5278c281edc6c72611c69e4309c3f5728dcd63d51413085e18c1d2e7
O=c1ccc(C2CC2)c2cc(C3CC3)ccn12
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D4;+0:3]1(-[c:4]2:[c:5]:[c:6]:[#7;a:7]:[c:8]:[c:9]:2)-[C:10]-[C:11]-1.O=P(-[N;H0;D2;+0:12]=[N+]=[N-])(-c1:c:c:c:c:c:1)-c1:c:c:c:c:c:1.[C;D1;H3:13]-[C:14](-[C;D1;H3:15])(-[C;D1;H3:16])-[OH;D1;+0:17]>>[C;D1;H3:13]-[C:14](-[C;D1;H3:15])(-[C;D1;H3:16])-[O;H0;D2;+0:17]-[C;H0;D3;+0:1](=[O...
null
[]
null
null
null
null
A sample of the product from Step 477d is heated with diphenylphosphoryl azide, t-butanol, triethylamine and dioxane. The solvents is removed under vacuum. The residue is dissolved in methylene chloride, washed with water and dried over MgSO4 and concentrated under vacuum. The title compound is purified by chromatograp...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Azide.Tertiary alcohol
Carbamic ester.Ether.Boc
C1CC1.c1ccccc1.c1ccccc1
C1CC1
C1CC1.c1ccn2ccccc2c1.C1CC1
HO-
O1CCOCC1
null
null
CC(C)(C)O.CCOC(=O)c1cc(C2CC2)c2c(C)c(C3(C(=O)O)CC3)c(F)cn2c1=O.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>O1CCOCC1>CCOC(=O)c1cc(C2CC2)c2c(C)c(C3(NC(=O)OC(C)(C)C)CC3)c(F)cn2c1=O
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-683f6b06ba0444c18452d135760784ee
N#Cc1ccccc1.[N-]=[N+]=[N-]>>c1ccc(-c2nnn[nH]2)cc1
Cl.CN(C=O)C.C(C1=CC=CC=C1)#N.[N-]=[N+]=[N-].[Na+]>>C1(=CC=CC=C1)C1=NN=NN1
[cH:1]1[cH:2][cH:3][c:4]([C:5]#[N:6])[cH:10][cH:11]1.[N+:7](=[N-:8])=[N-:9]>>[cH:1]1[cH:2][cH:3][c:4](-[c:5]2[n:6][n:7][n:8][nH:9]2)[cH:10][cH:11]1
N#Cc1ccccc1.[N-]=[N+]=[N-]
c1ccc(-c2nnn[nH]2)cc1
null
[Cl-].[Zn+2].[Cl-].[Cl-].[Zn+2].[Cl-]
O
Aromatic Heterocycle Formation
OtherReaction
237b84aaa459abf427f233dc6a07a1d9de824f980714e458423189bb68f60f12
d8c808528b7ee68720aaeebd35cb6a2a30e344748d0066102cdae99843b93cf0
c1ccc(-c2nnn[nH]2)cc1
[N-;H0;D1:1]=[N+;H0;D2:2]=[N-;H0;D1:3].[N;H0;D1;+0:4]#[C;H0;D2;+0:5]-[c;H0;D3;+0:6](:[c:7]:[c:8]):[c:9]:[c:10]>>[c:8]:[c:7]:[c;H0;D3;+0:6](-[c;H0;D3;+0:5]1:[n;H0;D2;+0:4]:[n;H0;D2;+0:2]:[n;H0;D2;+0:1]:[nH;D2;+0:3]:1):[c:9]:[c:10]
90.1
[{"value": 90.0, "product": "C1(=CC=CC=C1)C1=NN=NN1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.1, "product": "C1(=CC=CC=C1)C1=NN=NN1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Zinc chloride (3.3 g, 24.3 mmol, 0.5 eq) was added to 15 mL of N,N-dimethylformamide in small portions while maintaining the temperature below 60° C. The suspension of zinc chloride was cooled to room temperature and treated with 5.0 g of benzonitrile (48.5 mmol, 1.0 eq) followed by 3.2 g of sodium azide (48.5 mmol, 1....
10.6084/m9.figshare.5104873.v1
null
Nitrile
null
null
c1nnn[nH]1
c1ccccc1.c1nnn[nH]1
null
[Cl-].[Zn+2].[Cl-].[Cl-].[Zn+2].[Cl-].O
null
null
N#Cc1ccccc1.[N-]=[N+]=[N-]>[Cl-].[Zn+2].[Cl-].[Cl-].[Zn+2].[Cl-].O>c1ccc(-c2nnn[nH]2)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-6cdb42c88e1c4050ae28ae6ce211a291
ClC(c1ccccc1)(c1ccccc1)c1ccccc1.c1ccc(-c2nnn[nH]2)cc1>>c1ccc(-c2nnn(C(c3ccccc3)(c3ccccc3)c3ccccc3)n2)cc1
O.C(C)N(CC)CC.C1(=CC=CC=C1)C1=NN=NN1.C1(=CC=CC=C1)C(C1=CC=CC=C1)(C1=CC=CC=C1)Cl>>C1(=CC=CC=C1)C=1N=NN(N1)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1
Cl[C:9]([c:10]1[cH:11][cH:12][cH:13][cH:14][cH:15]1)([c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1)[c:22]1[cH:23][cH:24][cH:25][cH:26][cH:27]1.[cH:1]1[cH:2][cH:3][c:4](-[c:5]2[n:6][n:7][n:8][nH:28]2)[cH:29][cH:30]1>>[cH:1]1[cH:2][cH:3][c:4](-[c:5]2[n:6][n:7][n:8]([C:9]([c:10]3[cH:11][cH:12][cH:13][cH:14][cH:15]3)([c:16]3...
ClC(c1ccccc1)(c1ccccc1)c1ccccc1.c1ccc(-c2nnn[nH]2)cc1
c1ccc(-c2nnn(C(c3ccccc3)(c3ccccc3)c3ccccc3)n2)cc1
null
null
O1CCCC1.CC(=O)C
Heteroatom Alkylation and Arylation
OtherReaction
c814b61f4411b43802c99c033287485a681b4494d43aabc070529707b2f4fba2
677f263b618a481bcdc02c85060e6c44b1f44f328207057cd4782b98754b7773
c1ccc(-c2nnn(C(c3ccccc3)(c3ccccc3)c3ccccc3)n2)cc1
Cl-[C;H0;D4;+0:1](-[c:2](:[c:3]):[c:4])(-[c:5](:[c:6]):[c:7])-[c:8](:[c:9]):[c:10].[c:11]-[c:12]1:[#7;a:13]:[#7;a:14]:[n;H0;D2;+0:15]:[nH;D2;+0:16]:1>>[c:3]:[c:2](-[C;H0;D4;+0:1](-[c:5](:[c:6]):[c:7])(-[c:8](:[c:9]):[c:10])-[n;H0;D3;+0:15]1:[#7;a:14]:[#7;a:13]:[c:12](-[c:11]):[n;H0;D2;+0:16]:1):[c:4]
100
[{"value": 100.0, "product": "C1(=CC=CC=C1)C=1N=NN(N1)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 100.0, "product": "C1(=CC=CC=C1)C=1N=NN(N1)C(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
To a suspension of 5.0 g (34.2 mmol) of 5-phenyltetrazole in 55 mL of acetone was added 5.0 mL of triethylamine (3.6 g, 35.6 mmol, 1.04 eq). After 15 minutes, a solution of 10.0 g of triphenylmethyl chloride (35.9 mmol, 1.05 eq) in 20 mL of tetrahydrofuran was added and the mixture stirred at room temperature for one h...
10.6084/m9.figshare.5104873.v1
null
Tertiary halide
null
c1nnn[nH]1
c1nnn[nH]1
c1ccccc1.c1nnn[nH]1.c1ccccc1.c1ccccc1.c1ccccc1
HCl
O1CCCC1.CC(=O)C
null
0.25
ClC(c1ccccc1)(c1ccccc1)c1ccccc1.c1ccc(-c2nnn[nH]2)cc1>O1CCCC1.CC(=O)C>c1ccc(-c2nnn(C(c3ccccc3)(c3ccccc3)c3ccccc3)n2)cc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-4b176a6bf0704d8d9641aa04cf712b48
COC(=O)CC(C)(C)C(=O)O.OCc1ccccc1.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>>COC(=O)CC(C)(C)NC(=O)OCc1ccccc1
C(C1=CC=CC=C1)O.C1(=CC=CC=C1)P(=O)(C1=CC=CC=C1)N=[N+]=[N-].COC(CC(C(=O)O)(C)C)=O.C(C)N(CC)CC>>C(C1=CC=CC=C1)OC(=O)NC(CC(=O)OC)(C)C
O[C:10]([C:6]([CH2:5][C:3]([O:2][CH3:1])=[O:4])([CH3:7])[CH3:8])=[O:11].[OH:12][CH2:13][c:14]1[cH:15][cH:16][cH:17][cH:18][cH:19]1.[N-]=[N+]=[N:9]P(=O)(c1ccccc1)c1ccccc1>>[CH3:1][O:2][C:3](=[O:4])[CH2:5][C:6]([CH3:7])([CH3:8])[NH:9][C:10](=[O:11])[O:12][CH2:13][c:14]1[cH:15][cH:16][cH:17][cH:18][cH:19]1
COC(=O)CC(C)(C)C(=O)O.OCc1ccccc1.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
COC(=O)CC(C)(C)NC(=O)OCc1ccccc1
null
null
C1=CC=CC=C1
Protection
OtherReaction
1e58f6d4d49ad6167ca3c26ac5f42436cf03d7623c1813226bf87246cca930d2
aa6034c174fc48fa7e86a3e3e456bc7f49699778f1361299699fbbc966318b2e
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C;H0;D4;+0:3](-[C;D1;H3:4])(-[C;D1;H3:5])-[C:6]-[C:7](=[O;D1;H0:8])-[#8:9]-[C;D1;H3:10].O=P(-[N;H0;D2;+0:11]=[N+]=[N-])(-c1:c:c:c:c:c:1)-c1:c:c:c:c:c:1.[OH;D1;+0:12]-[C:13]-[c:14]>>[C;D1;H3:10]-[#8:9]-[C:7](=[O;D1;H0:8])-[C:6]-[C;H0;D4;+0:3](-[C;D1;H3:4])(-[C;D1;H3:5])-[NH;D2;+0:11]-[C;H...
75.1
[{"value": 75.0, "product": "C(C1=CC=CC=C1)OC(=O)NC(CC(=O)OC)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 75.1, "product": "C(C1=CC=CC=C1)OC(=O)NC(CC(=O)OC)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
To 14.7 g (91.8 mmol) of 2,2-dimethylbutanedioic acid-4-methyl ester in 150 mL of benzene was added 13 mL of triethylamine (9.4 g, 93 mmol) followed by 21.8 mL of diphenylphosphoryl azide (27.8 g, 101 mmol). The mixture was heated under nitrogen at reflux for 45 minutes then 19 mL (19.9 g, 184 mmol) of benzyl alcohol w...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Azide.Primary alcohol
Carbamic ester.Ether
c1ccccc1.c1ccccc1
null
c1ccccc1
HO-
C1=CC=CC=C1
null
16
COC(=O)CC(C)(C)C(=O)O.OCc1ccccc1.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>C1=CC=CC=C1>COC(=O)CC(C)(C)NC(=O)OCc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-17ae2f40160841b6afa956e1bf8b3a72
COC(=O)CC(C)(C)NC(=O)OCc1ccccc1>>CC(C)(CC(=O)O)NC(=O)OCc1ccccc1
COC(CC(C)(C)NC(=O)OCC1=CC=CC=C1)=O.[OH-].[Na+]>>C(C1=CC=CC=C1)OC(=O)NC(CC(=O)O)(C)C
C[O:7][C:5]([CH2:4][C:2]([CH3:1])([CH3:3])[NH:8][C:9](=[O:10])[O:11][CH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1)=[O:6]>>[CH3:1][C:2]([CH3:3])([CH2:4][C:5](=[O:6])[OH:7])[NH:8][C:9](=[O:10])[O:11][CH2:12][c:13]1[cH:14][cH:15][cH:16][cH:17][cH:18]1
COC(=O)CC(C)(C)NC(=O)OCc1ccccc1
CC(C)(CC(=O)O)NC(=O)OCc1ccccc1
null
null
CO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccccc1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
99.7
[{"value": 99.0, "product": "C(C1=CC=CC=C1)OC(=O)NC(CC(=O)O)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 99.7, "product": "C(C1=CC=CC=C1)OC(=O)NC(CC(=O)O)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
A solution of 18.27 g (68.9 mmol) of 3-benzyloxycarbonylamino-3-methylbutanoic acid methyl ester in 20 mL of methanol at room temperature was treated dropwise with 51 mL of 2N NaOH (102 mmol). The mixture was stirred at room temperature for 16 hours then transferred to a separatory funnel and washed with hexane (3×). T...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1
Other
CO
null
16
COC(=O)CC(C)(C)NC(=O)OCc1ccccc1>CO>CC(C)(CC(=O)O)NC(=O)OCc1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-a78a3036fc884a618177322321075319
CC(C)(CC(=O)O)NC(=O)OC(C)(C)C.CC[C@@H](N)C(=O)N(Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1)c1ccccc1>>CC[C@@H](NC(=O)CC(C)(C)NC(=O)OC(C)(C)C)C(=O)N(Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1)c1ccccc1
Cl.N[C@@H](C(=O)N(CC1=CC=C(C=C1)C1=C(C=CC=C1)C1=NN=NN1)C1=CC=CC=C1)CC.C(C)(C)(C)OC(=O)NC(CC(=O)O)(C)C>>C(C)(C)(C)OC(=O)NC(CC(=O)N[C@@H](C(=O)N(CC1=CC=C(C=C1)C1=C(C=CC=C1)C1=NN=NN1)C1=CC=CC=C1)CC)(C)C
O[C:5](=[O:6])[CH2:7][C:8]([CH3:9])([CH3:10])[NH:11][C:12](=[O:13])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18].[CH3:1][CH2:2][C@@H:3]([NH2:4])[C:19](=[O:20])[N:21]([CH2:22][c:23]1[cH:24][cH:25][c:26](-[c:27]2[cH:28][cH:29][cH:30][cH:31][c:32]2-[c:33]2[n:34][n:35][n:36][nH:37]2)[cH:38][cH:39]1)[c:40]1[cH:41][cH:42][cH:43][...
CC(C)(CC(=O)O)NC(=O)OC(C)(C)C.CC[C@@H](N)C(=O)N(Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1)c1ccccc1
CC[C@@H](NC(=O)CC(C)(C)NC(=O)OC(C)(C)C)C(=O)N(Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1)c1ccccc1
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
c1ccc(NCc2ccc(-c3ccccc3-c3nnn[nH]3)cc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4].[C:5]-[#7:6](-[c:7])-[C:8](=[O;D1;H0:9])-[C:10](-[C:11])-[NH2;D1;+0:12]>>[C:5]-[#7:6](-[c:7])-[C:8](=[O;D1;H0:9])-[C:10](-[C:11])-[NH;D2;+0:12]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C:4]
null
[]
null
null
null
null
Prepared as in Example 1, Step N from (R)-2-amino-N-phenyl-N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]butanamide, hydrochloride and 3-t-butoxycarbonylamino-3-methylbutanoic acid, N-hydroxysuccinimide ester. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1.c1nnn[nH]1.c1ccccc1
HO-
null
null
null
CC(C)(CC(=O)O)NC(=O)OC(C)(C)C.CC[C@@H](N)C(=O)N(Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1)c1ccccc1>>CC[C@@H](NC(=O)CC(C)(C)NC(=O)OC(C)(C)C)C(=O)N(Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1)c1ccccc1
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
ord-8d15441bff9244cf8bac899003f74801
CC(C)(C)OC(=O)N[C@H](Cc1c[nH]c2ccccc12)C(=O)O.OCc1ccccc1>>CC(C)(C)OC(=O)N[C@H](Cc1c[nH]c2ccccc12)C(=O)OCc1ccccc1
O.C(C)(C)(C)OC(=O)N[C@H](CC1=CNC2=CC=CC=C12)C(=O)O.C(C1=CC=CC=C1)O.Cl.CN(CCCN=C=NCC)C>>C(C1=CC=CC=C1)OC([C@H](NC(=O)OC(C)(C)C)CC1=CNC2=CC=CC=C12)=O
O[C:20]([C@H:9]([NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:10][c:11]1[cH:12][nH:13][c:14]2[cH:15][cH:16][cH:17][cH:18][c:19]12)=[O:21].[OH:22][CH2:23][c:24]1[cH:25][cH:26][cH:27][cH:28][cH:29]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][C@H:9]([CH2:10][c:11]1[cH:12][nH:13][c:14]2[cH:15][cH...
CC(C)(C)OC(=O)N[C@H](Cc1c[nH]c2ccccc12)C(=O)O.OCc1ccccc1
CC(C)(C)OC(=O)N[C@H](Cc1c[nH]c2ccccc12)C(=O)OCc1ccccc1
null
CN(C1=CC=NC=C1)C
C(Cl)Cl
Protection
Esterification of Carboxylic Acids
070670f68a20c1021da94fabee54def4688122fb721af5f52cd5a03630845d0e
0d8a72b7375d91aa7263e766e03a3cb7c4fa91e27abcd590409ff03b98eed690
O=C(CCc1c[nH]c2ccccc12)OCc1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[#7:5]-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9](-[C;D1;H3:10])(-[C;D1;H3:11])-[C;D1;H3:12].[OH;D1;+0:13]-[C:14]-[c:15]>>[C:4]-[C:3](-[#7:5]-[C:6](=[O;D1;H0:7])-[#8:8]-[C:9](-[C;D1;H3:10])(-[C;D1;H3:11])-[C;D1;H3:12])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[O;H0;D2;+0:13]-[C:14]-[c:15]
null
[]
null
null
null
null
Finely divided t-butoxycarbonyl-D-tryptophan (3 g, 10 mmol) was suspended in methylene chloride and benzyl alcohol (1.08 mL, 10 mmol) and 4-dimethylaminopyridine (0.12 g, 1 mmol) were added and stirred at room temperature. Solid 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.92 g, 10 mmol) was then adde...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary alcohol
Ester
null
null
c1ccc2[nH]ccc2c1.c1ccccc1
HO-
CN(C1=CC=NC=C1)C.C(Cl)Cl
null
null
CC(C)(C)OC(=O)N[C@H](Cc1c[nH]c2ccccc12)C(=O)O.OCc1ccccc1>CN(C1=CC=NC=C1)C.C(Cl)Cl>CC(C)(C)OC(=O)N[C@H](Cc1c[nH]c2ccccc12)C(=O)OCc1ccccc1