original_index
int64
2
1.77M
agent_000
stringlengths
1
540
agent_001
stringlengths
1
852
agent_002
stringlengths
1
247
date_of_experiment
timestamp[ns]date
extracted_from_file
stringclasses
489 values
grant_date
timestamp[ns]date
1976-01-01 00:01:00
2016-01-01 00:09:00
is_mapped
bool
1 class
procedure_details
stringlengths
8
24.5k
product_000
stringlengths
1
484
product_001
stringlengths
1
208
reactant_000
stringlengths
1
902
reactant_001
stringlengths
1
902
reactant_002
stringlengths
1
285
rxn_str
stringlengths
87
6.12k
rxn_time
float64
0
2.16k
solvent_000
stringclasses
446 values
solvent_001
stringclasses
405 values
solvent_002
stringclasses
330 values
temperature
float64
-230
30.1k
yield_000
float64
0
90,205,156,600B
yield_001
float64
0
100M
agent_003
null
agent_004
null
agent_005
null
agent_006
null
agent_007
null
agent_008
null
agent_009
null
agent_010
null
agent_011
null
agent_012
null
agent_013
null
agent_014
null
agent_015
null
agent_016
null
solvent_003
null
solvent_004
null
solvent_005
null
solvent_006
null
solvent_007
null
solvent_008
null
solvent_009
null
solvent_010
null
952,854
O=C([O-])[O-]
[K+]
null
null
ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8
2010-01-01T00:04:00
true
50 mL water and 8.5 g (61.51 mmol) K2CO3 were added to a solution of 4.5 g (14.98 mmol) 1-(7-dimethylaminomethyl-1,2,4,5-tetrahydro-3-benzazepin-3-yl)-2,2,2-trifluoroethanone in 50 mL MeOH and the reaction mixture was stirred for 72 h at RT. The reaction solution was evaporated down i.vac., the residue was combined with DCM, filtered to remove insoluble ingredients and evaporated down i.vac. The desired product was obtained in the form of a light-brown oil.
CN(C)Cc1ccc2c(c1)CCNCC2
null
CN(C)Cc1ccc2c(c1)CCN(C(=O)C(F)(F)F)CC2
null
null
O.C([O-])([O-])=O.[K+].[K+].[CH3:8][N:9]([CH2:11][C:12]1[CH:28]=[CH:27][C:15]2[CH2:16][CH2:17][N:18](C(=O)C(F)(F)F)[CH2:19][CH2:20][C:14]=2[CH:13]=1)[CH3:10]>CO>[CH3:8][N:9]([CH3:10])[CH2:11][C:12]1[CH:28]=[CH:27][C:15]2[CH2:16][CH2:17][NH:18][CH2:19][CH2:20][C:14]=2[CH:13]=1
72
CO
O
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
173,624
[Pd]
[Na+]
[OH-]
null
ord_dataset-3844acbccc714c04ab757ec4fca10bd0
1988-01-01T00:06:00
true
16.6 g (0.1 mol) of this o-nitrobenzaldoxime, 0.83 g of a 5% Pd-C catalyst, 12 g (0.2 mol) of glacial acetic acid and 100 ml of tetrahydrofurane were charged into a hermetically sealed glass container and stirred vigorously while charging hydrogen. Reaction was continued at temperatures of 25°-35° C. for 7 hours. After the reaction, the resulting mixture was filtered to remove the catalyst, was added with 8 g (0.2 mol) of sodium hydroxide and was subject to distillation. Thus, 9.7 g of o-aminobenzylamine was obtained. Yield 79.4%; Purity 99.4%; B.P. 91°-93° C./1 mmHg. M.P. 58°-61° C.
NCc1ccccc1N
null
O=[N+]([O-])c1ccccc1C=NO
[H][H]
null
[N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[CH:6]=[N:7]O)([O-])=O.C(O)(=O)C.[H][H].[OH-].[Na+]>[Pd].O1CCCC1>[NH2:1][C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[CH2:6][NH2:7]
7
C1CCOC1
CC(=O)O
null
null
79.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
896,855
null
null
null
null
ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded
2009-01-01T00:08:00
true
Similar procedure as described in example 131 was used, starting from (1-chloro-6-methoxy-isoquinolin-3-yl)-(1H-pyrazol-3-yl)-amine and 2-naphthaleneboronic acid to give (6-methoxy-1-naphthalen-2-yl-isoquinolin-3-yl)-(1H-pyrazol-3-yl)-amine. LC-MS m/e 367(MH+).
COc1ccc2c(-c3ccc4ccccc4c3)nc(Nc3cc[nH]n3)cc2c1
null
OB(O)c1ccc2ccccc2c1
COc1ccc2c(Cl)nc(Nc3cc[nH]n3)cc2c1
null
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH:14][C:15]2[CH:19]=[CH:18][NH:17][N:16]=2)[N:3]=1.[CH:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][C:21]=1B(O)O>>[CH3:13][O:12][C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[C:2]([C:22]1[CH:21]=[CH:20][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:23]=1)=[N:3][C:4]([NH:14][C:15]1[CH:19]=[CH:18][NH:17][N:16]=1)=[CH:5]2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
24,221
null
null
null
null
ord_dataset-fcf7c02bbb814fe696760b5fbfee16bb
1977-01-01T00:05:00
true
5-Amino-2-methyl-1,2,3,4-tetrahydroisoquinoline was reacted with 2,6-dimethoxybenzoyl chloride according to the procedure of Example 19 to yield 5-(2,6-dimethoxybenzamido)-2-methyl-1,2,3,4-tetrahydroisoquinoline; m.p. 191°-192° C. after recrystallization from benzene.
COc1cccc(OC)c1C(=O)Nc1cccc2c1CCN(C)C2
null
COc1cccc(OC)c1C(=O)Cl
CN1CCc2c(N)cccc2C1
null
[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH3:12])[CH2:7]2.[CH3:13][O:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:16]=1[C:17](Cl)=[O:18]>>[CH3:25][O:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:15]([O:14][CH3:13])[C:16]=1[C:17]([NH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH3:12])[CH2:7]2)=[O:18]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
395,216
CCN=C=NCCCN(C)C
Cl
null
null
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
1998-01-01T00:03:00
true
(S)-Boc-Diaminobutyric acid (25 g, 115 mmol), triethylamine (35 g, 344 mmol), and 1-hydroxybenzotriazole hydrate (19.3 g, 143 mmol) are dissolved in 300 mL of THF. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (27.4 g, 143 mmol) is added to the solution. The solution is heated at 60° C. over 15 min. A white precipitate forms and the solution is kept at 60° C. for 4 h. After this time, the solution is filtered and the collected liquid is concentrated. The crude product is purified by column chromatography eluting with a gradient of 1% MeOH/CH2Cl2 to 3% MeOH/CH2Cl2 to afford the title compound (19.6 g, 98 mmol) as a white solid.
CC(C)(C)OC(=O)N[C@H]1CCNC1=O
null
O
C[C@H](C(=O)OC(C)(C)C)C(N)(N)C(=O)O
On1nnc2ccccc21
[C:1]([C@@H](C)C(N)(N)C(O)=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(CC)CC)C.[OH2:23].O[N:25]1[C:29]2C=C[CH:32]=[CH:33][C:28]=2[N:27]=N1.Cl.CN(C)CCCN=C=NCC>C1COCC1>[C:4]([O:3][C:1](=[O:2])[NH:27][C@H:28]1[CH2:33][CH2:32][NH:25][C:29]1=[O:23])([CH3:5])([CH3:6])[CH3:7]
4
C1CCOC1
CCN(CC)CC
null
60
null
85.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,566,452
null
null
null
null
ord_dataset-4e54080057a44c3887653391e24c90b6
2015-01-01T00:03:00
true
(2-Chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidine-6-carboxaldehyde) was reacted with (2-methoxy-ethyl)-methyl-piperidin-4-yl-amine using standard reductive amination conditions to give [1-(2-chloro-4-morpholin-4-yl-thieno[2,3-d]pyrimidin-6-ylmethyl)-piperidin-4-yl]-(2-methoxy-ethyl)-methyl amine as a solid, which was reacted with 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine according to General Procedure A. The resulting solid was triturated with diethyl ether and methanol to give 366 as an off white solid (53% yield). NMR (CDCl3, 400 MHz), 1.59-1.70 (2H, m), 1.78-1.81 (2H, m), 2.10 (2H, t, J=12.3), 2.37 (3H, s), 2.42-2.48 (1H, m), 2.70 (2H, t, J=5.9), 3.07 (2H, d, J=11.3), 3.41 (3H, s), 3.49-3.54 (2H, m), 3.78 (2H, s), 3.92-3.94 (4H, m), 3.97-4.00 (4H, m), 4.67 (2H, br s), 6.60 (1H, d, J=8.9), 7.13 (1H, s), 8.51 (1H, dd, J=8.6 and 2.2), 9.20 (1H, d, J=1.6). MS: (ESI+): MH+=498
COCCN(C)C1CCN(Cc2cc3c(N4CCOCC4)nc(Cl)nc3s2)CC1
null
COCCN(C)C1CCNCC1
O=Cc1cc2c(N3CCOCC3)nc(Cl)nc2s1
null
[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[CH:10]=[C:9]([CH:11]=O)[S:8][C:6]=2[N:7]=1.[CH3:19][O:20][CH2:21][CH2:22][N:23]([CH3:30])[CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>>[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[CH:10]=[C:9]([CH2:11][N:27]3[CH2:28][CH2:29][CH:24]([N:23]([CH2:22][CH2:21][O:20][CH3:19])[CH3:30])[CH2:25][CH2:26]3)[S:8][C:6]=2[N:7]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
322,858
null
null
null
null
ord_dataset-24ad29d930104afea313b6c3bd11099e
1996-01-01T00:01:00
true
64 g of 4-methyl-2-(1-chloro-2,2,2-trifluoroethyl)-2-trifluoromethyl-1,3-benzodioxole from Example 9 were dissolved in 500 ml of carbon tetrachloride, and 36 g of N-bromosuccinimide and 0.5 g of AIBN (azoisobutyronitrile) were added. The mixture was stirred under reflux for 3 hours and then cooled and filtered. The solvent was stripped off and the residue was distilled in vacuo. The yield was 57 g (71% of theory), and the boiling point was 80°-82° C. under 0.1 mbar. The NMR spectra showed the following characteristic absorptions: 1H-NMR: 4.72 ppm.
FC(F)(F)C(Cl)C1(C(F)(F)F)Oc2cccc(CBr)c2O1
null
Cc1cccc2c1OC(C(Cl)C(F)(F)F)(C(F)(F)F)O2
O=C1CCC(=O)N1Br
null
[CH3:1][C:2]1[C:10]2[O:9][C:8]([CH:15]([Cl:20])[C:16]([F:19])([F:18])[F:17])([C:11]([F:14])([F:13])[F:12])[O:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[Br:21]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:21][CH2:1][C:2]1[C:10]2[O:9][C:8]([CH:15]([Cl:20])[C:16]([F:19])([F:18])[F:17])([C:11]([F:12])([F:13])[F:14])[O:7][C:6]=2[CH:5]=[CH:4][CH:3]=1
null
ClC(Cl)(Cl)Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,296,526
null
null
null
null
ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c
2013-01-01T00:05:00
true
Anhydrous ethylene glycol (301.3 g, 4.85 mol) and triethylamine (28 mL, 200 mmol) were diluted with dry tetrahydrofuran (100 mL). The reaction mixture was cooled in an ice-water bath and a solution of α-bromoisobutyryl bromide (12 mL, 97.1 mmol) in dry tetrahydrofuran (50 mL) was slowly added while stirring. The mixture was stirred in the cooling bath for 1 h and then at room temperature for 16 h. The reaction mixture was then poured into water (800 mL) and extracted with dichloromethane (6×100 mL). The organic fractions were combined, washed with acidic water (pH=4), dried over MgSO4 and evaporated to dryness to afford 17.477 g (yield=85.3%) of a very pale yellow liquid. 1H NMR (CDCl3, δ, ppm): 4.30-4.19 (m, 2H), 3.86-3.75 (m, 2H), 2.86-2.47 (broad peak, 1H, OH), 1.89 (s, 6H). 13C NMR (CDCl3, δ): 171.95, 67.40, 60.63, 55.89, 30.72.
CC(C)(Br)C(=O)OCCO
null
CC(C)(Br)C(=O)Br
OCCO
null
[CH2:1]([OH:4])[CH2:2][OH:3].C(N(CC)CC)C.[Br:12][C:13]([CH3:18])([CH3:17])[C:14](Br)=[O:15].O>O1CCCC1>[Br:12][C:13]([CH3:18])([CH3:17])[C:14]([O:3][CH2:2][CH2:1][OH:4])=[O:15]
16
CCN(CC)CC
C1CCOC1
O
null
85.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,131,416
null
null
null
null
ord_dataset-285df12e34cd46e993e3c8ebc3a8962a
2012-01-01T00:01:00
true
Following the procedure as described in PREPARATION 1E, and making non-critical variations to replace 4-bromo-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-indol-2-one with 3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1-pentyl-1,3-dihydro-2H-indol-2-one, the title compound was obtained (46%): MS (ES+) m/z 368.3 (M+1), 380.4 (M+23).
CCCCCN1C(=O)C(CO)(c2cc3c(cc2O)OCC3)c2ccccc21
null
CCCCCN1C(=O)C(c2cc3c(cc2O)OCO3)c2c(Br)cccc21
CCCCCN1C(=O)C(c2cc3c(cc2O)OCC3)c2ccccc21
null
BrC1C=CC=C2C=1C(C1C(O)=CC3OCOC=3C=1)[C:5](=[O:16])N2CCCCC.[OH:27][C:28]1[C:36]([CH:37]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[N:39]([CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[C:38]2=[O:51])=[CH:35][C:31]2[CH2:32][CH2:33][O:34][C:30]=2[CH:29]=1>>[OH:27][C:28]1[C:36]([C:37]2([CH2:5][OH:16])[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[N:39]([CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[C:38]2=[O:51])=[CH:35][C:31]2[CH2:32][CH2:33][O:34][C:30]=2[CH:29]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,168,010
null
null
null
null
ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880
2012-01-01T00:05:00
true
A mixture of methyl dimethoxyacetate (1.41 g, 10.4 mmol) and 2-chlorobenzylamine (1.45 g, 9.73 mmol) in a microwave vial was sealed and heated in the microwave reactor to 130° C. for 30 min and then to 140° C. for 40 min. The reaction solution was dissolved in EtOAc (≈60 mL) and washed with dil. HCl, water, sat. Na2CO3 solution, and brine, and dried over MgSO4. The EtOAc extract was filtered, concentrated, and dried in vacuo overnight, giving the title compound as pale yellow oil. 1H NMR (400 MHz, CDCl3): δ=7.41-7.35 & 7.27-7.22 (AA′BB′, 4H), 6.98 (brs, 1H), 4.74 (s, 1H), 4.58 (d, J=6.0 Hz, 2H), 3.40 (s, 6H). MS(ES+): m/z=266.05/268.01 (41/13) [MNa′], 244.07/246.02 (86/58) [MH+], 212.03/214.02 (56/21) [MH+-MeOH], 180.07/182.05 (63/26) [MH+-2 MeOH]. HPLC: tR=2.87 min (polar—5 min, ZQ3).
COC(OC)C(=O)NCc1ccccc1Cl
null
NCc1ccccc1Cl
COC(=O)C(OC)OC
null
[CH3:1][O:2][CH:3]([O:8][CH3:9])[C:4](OC)=[O:5].[Cl:10][C:11]1[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=1[CH2:13][NH2:14]>CCOC(C)=O>[Cl:10][C:11]1[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=1[CH2:13][NH:14][C:4](=[O:5])[CH:3]([O:8][CH3:9])[O:2][CH3:1]
0.67
CCOC(C)=O
null
null
130
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
823,850
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
null
null
null
ord_dataset-0ca5627a13c049a99463095023b09fe5
2008-01-01T00:06:00
true
3-Phenyl-5-(tri-n-butylstannyl)pyridazine (50 mg, 0.11 mmol), methyl 3-bromothiophene-2-carboxylate (30 mg) and Pd(PPh3)4 (5 mg) in THF (2 ml) were combined and heated to 150° C. for 600 seconds in a Smith Synthesizer microwave reactor. The reaction was diluted with CH2Cl2 (6 ml) and H2O (2 ml) then poured into PTFE (5 μM) fritted syringe barrels. The organic phase was collected and concentrated to leave 85 mg of crude product. Part of the sample was purified by HPLC with mass triggered collection of fractions to give the title compound (3.9 mg). δH (400 MHz, d6 DMSO) 3.73 (3H, s), 7.52-7.62 (4H, m), 8.10 (1H, d, J 8.0), 8.22 (2H, dd, J 1.6 and 8.0), 8.35 (1H, d, J 4.0), 9.33 (1H, d, J 4.0); m/z (ES+) (MH+) 297.
COC(=O)c1sccc1-c1cnnc(-c2ccccc2)c1
null
COC(=O)c1sccc1Br
CCCC[Sn](CCCC)(CCCC)c1cnnc(-c2ccccc2)c1
null
[C:1]1([C:7]2[N:8]=[N:9][CH:10]=[C:11]([Sn](CCCC)(CCCC)CCCC)[CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:27]1[CH:31]=[CH:30][S:29][C:28]=1[C:32]([O:34][CH3:35])=[O:33]>C1COCC1.C(Cl)Cl.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:35][O:34][C:32]([C:28]1[S:29][CH:30]=[CH:31][C:27]=1[C:11]1[CH:12]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]=[N:9][CH:10]=1)=[O:33]
null
ClCCl
C1CCOC1
O
150
12
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
21,453
null
null
null
null
ord_dataset-39f318aa6ec5450182abaf3662294306
1977-01-01T00:03:00
true
A solution of ethyl 1-(7-chloroquinazolin-4-yl)-5-hydroxy-2-methylindol-3-ylacetate (1.0g.) in dry dimethyl-formamide (10ml.); dried by distillation from calcium hydride, and stored over sodium alumino-silicate) was added to sodium hydride (0.068g.), and the mixture was stirred under a slight vacuum (ca 150mm. Hg) at room temperature for 15 minutes. n-Propyl iodide (0.9g.) was added to the resulting clear solution, and the mixture stirred at room temperature overnight. The solution was added to water (300ml.) and extracted with ethyl acetate (3 × 40ml.). The combined extracts were washed with a saturated solution of sodium chloride (30ml.), dried (MgSO4), and then evaporated in vacuo. The yellow oil thus obtained was treated with tetrachloroethylene (100ml.) and the solution evaporated in vacuo. This process was then replaced with ethanol (50ml.) to give ethyl 1-(7chloroquinazolin-4-yl)-2-methyl-5-n-propoxyindol-3-ylacetate as a stiff yellow syrup [NMR: 2-CH3 at 7.65 τ; pure by TLC (systems A and D)].
CCCOc1ccc2c(c1)c(CC(=O)OCC)c(C)n2-c1ncnc2cc(Cl)ccc12
null
ClC(Cl)=C(Cl)Cl
CCOC(=O)Cc1c(C)n(-c2ncnc3cc(Cl)ccc23)c2ccc(O)cc12
CN(C)C=O
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:12]3[C:20]4[C:15](=[CH:16][C:17]([OH:21])=[CH:18][CH:19]=4)[C:14]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:13]3[CH3:28])=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.Cl[C:30](Cl)=[C:31](Cl)Cl.[CH3:35]N(C)C=O>>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:12]3[C:20]4[C:15](=[CH:16][C:17]([O:21][CH2:35][CH2:30][CH3:31])=[CH:18][CH:19]=4)[C:14]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:13]3[CH3:28])=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1
0.25
null
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
993,946
null
null
null
null
ord_dataset-b6d8835b0c934476a36e6149e7597487
2010-01-01T00:09:00
true
2-(2,4-Dichlorophenyl)-1-(4-hydroxyphenyl)-5-methyl-N-piperidin-1-yl-1H-imidazole-4-carboxamide, prepared as described in Ex. 2, Step 1 (50 mg, 0.11 mmol) was dissolved in dichloromethane (3.0 ml), cooled to 0° C. and triethylamine (20 μl, 0.13 mmol) was added to the mixture. The resulting mixture was cooled to −78° C. and 3-methylbutane-1-sulfonyl chloride (23 mg, 0.13 mmol) was carefully added. The reaction was stirred at −78° C. for 1.5 h. Water was added to the reaction, the product extracted with dichloromethane and dried. The solvent was removed under reduced pressure and separation by preparatory HPLC gave the title compound (46 mg, 71%) as a solid.
Cc1c(C(=O)NN2CCCCC2)nc(-c2ccc(Cl)cc2Cl)n1-c1ccc(OS(=O)(=O)CCC(C)C)cc1
null
CC(C)CCS(=O)(=O)Cl
Cc1c(C(=O)NN2CCCCC2)nc(-c2ccc(Cl)cc2Cl)n1-c1ccc(O)cc1
null
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]([C:24]2[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=2)[C:11]([CH3:23])=[C:12]([C:14]([NH:16][N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:15])[N:13]=1.C(N(CC)CC)C.[CH3:38][CH:39]([CH3:46])[CH2:40][CH2:41][S:42](Cl)(=[O:44])=[O:43].O>ClCCl>[CH3:38][CH:39]([CH3:46])[CH2:40][CH2:41][S:42]([O:30][C:27]1[CH:26]=[CH:25][C:24]([N:10]2[C:11]([CH3:23])=[C:12]([C:14]([NH:16][N:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)=[O:15])[N:13]=[C:9]2[C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])=[CH:29][CH:28]=1)(=[O:44])=[O:43]
1.5
CCN(CC)CC
ClCCl
O
0
71
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,560,415
null
null
null
null
ord_dataset-4e54080057a44c3887653391e24c90b6
2015-01-01T00:03:00
true
3,5-Dichloro-N-(2-hydroxyethyl)-4-(1H-pyrrolo[3,2-c]pyridin-1-ylcarbonyl)benzamide (Compound No. 75) was prepared using 1H-pyrrolo[3,2-c]pyridine and 2,6-dichloro-4-[(2-hydroxyethyl)carbamoyl]benzoic acid.
O=C(NCCO)c1cc(Cl)c(C(=O)n2ccc3cnccc32)c(Cl)c1
null
O=C(NCCO)c1cc(Cl)c(C(=O)O)c(Cl)c1
c1cc2[nH]ccc2cn1
null
[NH:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=[CH:2]1.[Cl:10][C:11]1[CH:19]=[C:18]([C:20](=[O:25])[NH:21][CH2:22][CH2:23][OH:24])[CH:17]=[C:16]([Cl:26])[C:12]=1[C:13](O)=[O:14]>>[Cl:10][C:11]1[CH:19]=[C:18]([CH:17]=[C:16]([Cl:26])[C:12]=1[C:13]([N:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=[CH:2]1)=[O:14])[C:20]([NH:21][CH2:22][CH2:23][OH:24])=[O:25]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,583,430
null
null
null
null
ord_dataset-380e279f82154dba9e08ab51b3bdd08a
2015-01-01T00:05:00
true
2.45 g (0.01 mmol) of 5-nitro-1H,3H-benzo[de]isochromene-1,3-dione and 1.23 g (0.01 mmol) of 6-aminohexanoic acid was alloyed with at 210-220° C. for 35 min. The obtained crude 6-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-2-yl)hexanoic acid was recrystallized from ethanol. Yield 1.7 g (48%). The product was dissolved in 50 mL of ethanol and was added dropwise to the hot solution of 8 g of tin chloride in 9 mL of hydrochloric acid at boiling. The reaction mixture was boiled for 4 h, then poured with water and neutralized with 5% solution of sodium hydrate. Yellow sediment was filtered and purified by a column chromatography (Silica gel, chloroform). Yield 1.1 g of ethyl 6-(5-amino-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-2-yl)hexanoate (31.5% counting on 5-nitro-1H,3H-benzo[de]isochromene-1,3-dione). M.P. 108-110° C.
O=C(O)CCCCCN1C(=O)c2cccc3cc([N+](=O)[O-])cc(c23)C1=O
null
O=C1OC(=O)c2cc([N+](=O)[O-])cc3cccc1c23
NCCCCCC(=O)O
null
[N+:1]([C:4]1[CH:5]=[C:6]2[CH:15]=[CH:14][CH:13]=[C:12]3[C:7]2=[C:8]([CH:18]=1)[C:9](=[O:17])O[C:11]3=[O:16])([O-:3])=[O:2].[NH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26]>>[N+:1]([C:4]1[CH:5]=[C:6]2[CH:15]=[CH:14][CH:13]=[C:12]3[C:7]2=[C:8]([CH:18]=1)[C:9](=[O:17])[N:19]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])[C:11]3=[O:16])([O-:3])=[O:2]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
565,129
O=S([O-])[O-]
[Na+]
null
null
ord_dataset-5c8a417a8ba04cf0b7f78b9db9af1d01
2002-01-01T00:10:00
true
3,5-Bis(trifluromethyl)styrene (13 g) was dissolved in a mixture of water (270 ml) and 2-methylpropan-2-ol (270 ml) and cooled to 0° C. AD-mix-α (76 g) was added in one portion and the reaction left to warm to room temperature over 72 hours. The mixture was then cooled to 0° C., sodium sulfite (81 g) added and the reaction mixture extracted into ethyl acetate (3×250 ml). The combined organics were dried (brine, MgSO4) and concentrated under reduced pressure to afford the product as a crude orange solid which was purified on silica eluting with 35% ethyl acetate/iso-hexane to afford the product as a crystalline white solid (chiral hplc, ee 92.2%). This was recrystallised from toluene to give the title compound as a white fibres (chiral hplc, ee 96.2%).
OC[C@@H](O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
null
CC[C@@H]1CN2CC[C@@H]1C[C@@H]2[C@H](Oc1nnc(O[C@H](c2ccnc3ccc(OC)cc23)[C@H]2C[C@@H]3CCN2C[C@@H]3CC)c2ccccc12)c1ccnc2ccc(OC)cc12
C=Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
O
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[CH:6]=[CH2:7].CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C([O:38]C)C=C4)N(CC2)C1.S([O-])([O-])=O.[Na+].[Na+].[OH2:81]>CC(O)(C)C>[F:1][C:2]([F:15])([F:16])[C:3]1[CH:4]=[C:5]([C@H:6]([OH:38])[CH2:7][OH:81])[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1
null
CC(C)(C)O
null
null
0
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
500,249
CS(=O)(=O)Cl
O=C([O-])O
[Na+]
null
ord_dataset-18e9ed24dbd44e98b33bdc22aa7580a8
2001-01-01T00:04:00
true
To a solution of N-[2-[1-formyl-2,3-dihydro-5-hydroxy-4-(2-hydroxyethyl)indol-3-yl]ethyl]propionamide (0.8 g, 2.61 mmol) in pyridine (10 mL) was added methansulfonyl chloride (0.2 mL, 2.61 mmol.) around −10° C. The mixture was stirred for 20 minutes while keeping the temperature −10 to 5° C. To this was added additional methansulfonyl chloride (0.1 mL, 1.3 mmol.) and the mixture was stirred for further 15 minutes at the same temperature. The mixture was diluted with ethyl acetate(10 mL). Saturated aqueous sodium hydrogen carbonate solution (10 mL) was added slowly and the mixture was stirred for 30 minutes at room temperature. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with 2N-hydrochloric acid and water, dried over anhydrous magnesium sulfate and evaporated. The residue was purified by silica gel column chromatography (chloroform:methanol=9:1) to afford the title compound (yield 0.25 g, 33%).
CCC(=O)NCCC1CN(C=O)c2ccc3c(c21)CCO3
null
CCC(=O)NCCC1CN(C=O)c2ccc(O)c(CCO)c21
null
null
[CH:1]([N:3]1[C:11]2[C:6](=[C:7]([CH2:13][CH2:14][OH:15])[C:8](O)=[CH:9][CH:10]=2)[CH:5]([CH2:16][CH2:17][NH:18][C:19](=[O:22])[CH2:20][CH3:21])[CH2:4]1)=[O:2].CS(Cl)(=O)=O.C(=O)([O-])O.[Na+]>N1C=CC=CC=1.C(OCC)(=O)C>[CH:1]([N:3]1[C:11]2[C:6](=[C:7]3[CH2:13][CH2:14][O:15][C:8]3=[CH:9][CH:10]=2)[CH:5]([CH2:16][CH2:17][NH:18][C:19](=[O:22])[CH2:20][CH3:21])[CH2:4]1)=[O:2]
0.33
c1ccncc1
CCOC(C)=O
null
null
null
33.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,221,955
Cl
null
null
null
ord_dataset-cde802cdb7434a5f82a22981ccaefc4e
2012-01-01T00:11:00
true
A mixture of 4-piperidone hydrochloride monohydrate (31.2 g, 203 mmol) and tert-butylcarbazate (26.8 g, 203 mmol) in 100 mL MeOH is stirred over weekend at RT and then concentrated in vacuo. The residue is crystallized from ethyl acetate. Yield: 47.5 g.
CC(C)(C)OC(=O)NN=C1CCNCC1
null
O=C1CCNCC1
CC(C)(C)OC(=O)NN
null
O.[ClH:2].[NH:3]1[CH2:8][CH2:7][C:6](=O)[CH2:5][CH2:4]1.[C:10]([O:14][C:15](=[O:18])[NH:16][NH2:17])([CH3:13])([CH3:12])[CH3:11]>CO>[ClH:2].[C:10]([O:14][C:15]([NH:16][N:17]=[C:6]1[CH2:7][CH2:8][NH:3][CH2:4][CH2:5]1)=[O:18])([CH3:13])([CH3:12])[CH3:11]
null
O
CO
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
653,948
null
null
null
null
ord_dataset-fe016e2f90e741a590ad77fd5933161f
2004-01-01T00:11:00
true
Prepared analogously to Example 2 from 9-(4-bromo-butyl)-9H-xanthene-9-carboxylic acid-(2,2,2-trifluoro-ethyl)-amide and 2-[1.4]diazepan-1-yl-quinoline.
O=C(NCC(F)(F)F)C1(CCCCN2CCCN(c3ccc4ccccc4n3)CC2)c2ccccc2Oc2ccccc21
null
O=C(NCC(F)(F)F)C1(CCCCBr)c2ccccc2Oc2ccccc21
c1ccc2nc(N3CCCNCC3)ccc2c1
null
[F:1][C:2]([F:27])([F:26])[CH2:3][NH:4][C:5]([C:7]1([CH2:21][CH2:22][CH2:23][CH2:24]Br)[C:20]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:14][C:13]2[C:8]1=[CH:9][CH:10]=[CH:11][CH:12]=2)=[O:6].[N:28]1([C:35]2[CH:44]=[CH:43][C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[N:36]=2)[CH2:34][CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1>>[F:1][C:2]([F:27])([F:26])[CH2:3][NH:4][C:5]([C:7]1([CH2:21][CH2:22][CH2:23][CH2:24][N:31]2[CH2:32][CH2:33][CH2:34][N:28]([C:35]3[CH:44]=[CH:43][C:42]4[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=4)[N:36]=3)[CH2:29][CH2:30]2)[C:20]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:14][C:13]2[C:8]1=[CH:9][CH:10]=[CH:11][CH:12]=2)=[O:6]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
616,105
Cc1ccc2c(c1)C(=O)c1ccccc1C2=O
O=C1c2ccccc2C(=O)c2ccccc21
null
null
ord_dataset-31fc6d0085ca4d8dbbcd3a5fa9dcedfb
2003-01-01T00:11:00
true
1,4-dihydroxyanthraquinone; anthraquinone; 2-methylanthraquinone,
O=c1c2ccccc2oc2ccccc12
null
O=C1c2ccccc2C(=O)c2c(O)ccc(O)c21
null
null
O[C:2]1[C:15]2C(=O)[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([OH:18])=[CH:4][CH:3]=1.C1C2C(=O)C3C(=CC=CC=3)C(=O)C=2C=CC=1.CC1C=CC2C(=O)C3C(=CC=CC=3)C(=O)C=2C=1>>[CH:15]1[C:6]2[C:7](=[O:17])[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[O:18][C:5]=2[CH:4]=[CH:3][CH:2]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
263,387
BrB(Br)Br
null
null
null
ord_dataset-a7bd0db0684c464bb02ff6a36065fee3
1993-01-01T00:03:00
true
To 5.02 g of 1-[2-hydroxy-4-[4-(2,3-dimethoxyphenyl)butoxy]-3-propylphenyl]ethanone in 300 mL of methylene chloride stirred and cooled at -70° was added 39 mL of 1M boron tribromide in methylene chloride. The reaction mixture was stirred at -70° for 30 minutes and kept at -20° for 5.5 hours. Workup as in Example 32 and recrystallization from acetone-hexane gave 3.81 g (82% yield), mp 103°-105° of 1-[2-hydroxy-4-[4-(2,3-dihydroxyphenyl)butoxy]-3-propylphenyl]ethanone.
CCCc1c(OCCCCc2cccc(O)c2O)ccc(C(C)=O)c1O
null
CCCc1c(OCCCCc2cccc(OC)c2OC)ccc(C(C)=O)c1O
null
null
[OH:1][C:2]1[C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22]C)[C:17]=2[O:24]C)[CH:5]=[CH:4][C:3]=1[C:26](=[O:28])[CH3:27].B(Br)(Br)Br>C(Cl)Cl>[OH:1][C:2]1[C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[C:17]=2[OH:24])[CH:5]=[CH:4][C:3]=1[C:26](=[O:28])[CH3:27]
0.5
ClCCl
null
null
null
null
82
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
618,475
O=C([O-])[O-]
[Na+]
null
null
ord_dataset-2952e63264f5422a84e12cca1e0541ee
2003-01-01T00:12:00
true
cis-3-Iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (141 mg, 0.319 mmol), 4-[(benzylamino)carbonyl]-3-methoxyphenylboronic acid (100 mg, 0.351 mmol), palladium tetrakistriphenyphosphine (22 mg, 0.019 mmol) and sodium carbonate (81 mg, 0.765 mmol) were mixed with ethylene glycol dimethyl ether (4 mL) and water (2 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (95:5) as mobile phase to give cis-N1-benzyl-4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxybenzamide (126 mg, 71%). 1H NMR (CDCl3) δ 1.83 (m, 6H), 2.34 (s, 3H), 2.45 (m, 11H), 4.02 (s, 3H), 4.43 (d, J=5.66 Hz, 2H), 4.95 (m, 1H), 5.52 (bs, 2H), 7.37 (m, 7H), 8.18 (m, 1H), 8.41 (m, 1H); LC/MS (Micromass-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4.5 min.(B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 3.5 mL/min.): MH+ =555.5, Rt=2.65 min.
COc1cc(-c2nn([C@H]3CC[C@@H](N4CCN(C)CC4)CC3)c3ncnc(N)c23)ccc1C(=O)NCc1ccccc1
null
CN1CCN([C@H]2CC[C@@H](n3nc(I)c4c(N)ncnc43)CC2)CC1
COc1cc(B(O)O)ccc1C(=O)NCc1ccccc1
null
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C@H:12]2[CH2:17][CH2:16][C@@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.[CH2:25]([NH:32][C:33]([C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][C:36]=1[O:44][CH3:45])=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[CH2:25]([NH:32][C:33](=[O:34])[C:35]1[CH:40]=[CH:39][C:38]([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[N:8][C:9]=3[NH2:11])[N:4]([C@H:12]3[CH2:17][CH2:16][C@@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:3]=2)=[CH:37][C:36]=1[O:44][CH3:45])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
null
O
COCCOC
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
897,201
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
O=C([O-])[O-]
[K+]
null
ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded
2009-01-01T00:08:00
true
To a stirring, degassed mixture of 7-bromo-8-iodo-2-isobutyl-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (50 mg, 0.13 mmol), 4-cyanophenylboronic acid (40 mg, 0.28 mmol), and tetrakis(triphenylphosphine)palladium (7 mg, 0.006 mmol) in dioxane (1.0 mL) at 20° C. was added K2CO3 (40 mg, 0.25 mmol) in water (0.3 mL). The resulting reaction mixture was heated in a microwave reactor at 200° C. for 10 min under argon. Analysis by HPLC/MS indicated that starting material had been consumed. The reaction mixture was brought to room temperature and was concentrated under reduced pressure. The crude product was purified by reverse phase preparative HPLC (acetonitrile-water-TFA) to isolate the title compound (15 mg, 0.038 mmol) as a yellow solid. MS: [M+H]+=394.
CC(C)Cn1nc2c(-c3ccc(C#N)cc3)c(-c3ccc(C#N)cc3)ccn2c1=O
null
N#Cc1ccc(B(O)O)cc1
CC(C)Cn1nc2c(I)c(Br)ccn2c1=O
null
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8](=[O:15])[N:9]([CH2:11][CH:12]([CH3:14])[CH3:13])[N:10]=[C:4]2[C:3]=1I.[C:17]([C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1)#[N:18].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:17]([C:19]1[CH:24]=[CH:23][C:22]([C:2]2[CH:7]=[CH:6][N:5]3[C:8](=[O:15])[N:9]([CH2:11][CH:12]([CH3:14])[CH3:13])[N:10]=[C:4]3[C:3]=2[C:22]2[CH:23]=[CH:24][C:19]([C:17]#[N:18])=[CH:20][CH:21]=2)=[CH:21][CH:20]=1)#[N:18]
null
C1COCCO1
O
null
200
null
29.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,261,855
[K+]
[OH-]
null
null
ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0
2013-01-01T00:02:00
true
Aqueous potassium hydroxide (50% w/v, 0.2 ml) was added to a suspension of methyl 2-hydroxy-5-isopropyl-4-methoxybenzoate (420 mg, 1.88 mmol) in methanol (5 ml) and water (2 ml) and the mixture was stirred and held at reflux for 3 hours. Upon cooling to room temperature the organic solvent was removed in vacuo and the residue acidified by the addition of 2M hydrochloric acid (10 ml). The solid material was collected by suction filtration, rinsed with water (2×10 ml) and sucked dry under reduced pressure to afford 2-hydroxy-5-isopropyl-4-methoxybenzoic acid (275 mg, 70%) as a colourless solid. 1H NMR (DMSO-d6) 13.50 (1H, br s), 11.40 (1H, br s), 7.53 (1H, s), 6.51 (1H, s), 3.83 (3H, s), 3.12 (1H, m), 1.13 (6H, d). MS: [M+H]+ 211.
COc1cc(O)c(C(=O)O)cc1C(C)C
null
COC(=O)c1cc(C(C)C)c(OC)cc1O
null
null
[OH-].[K+].[OH:3][C:4]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([CH:16]([CH3:18])[CH3:17])=[CH:10][C:5]=1[C:6]([O:8]C)=[O:7]>CO.O>[OH:3][C:4]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([CH:16]([CH3:18])[CH3:17])=[CH:10][C:5]=1[C:6]([OH:8])=[O:7]
null
O
CO
null
25
69.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,099,864
null
null
null
null
ord_dataset-af85e6f81c2d49f08086afd6d9e6959c
2011-01-01T00:10:00
true
When the reaction ended, the mixture was allowed to cool and was left to stand overnight. The crystals that precipitated were filtered out, washed with dimethyl formamide, and dried under reduced pressure, yielding 3.0 g of intermediate B. To 2.0 g of intermediate B was then added 20 mL of p-toluenesulfonic acid methyl ester, and the mixture was stirred with heating for 6 hours at 120° C. The mixture was allowed to cool, after which 30 mL of ethyl acetate was added, and stirring was conducted for 30 minutes. The precipitating crystals were filtered out and dried, yielding 2.75 g of p-toluenesulfonate of V-1.
Cc1ccc(S(=O)(=O)O)cc1
null
COS(=O)(=O)c1ccc(C)cc1
null
null
C[O:2][S:3]([C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][CH:7]=1)(=[O:5])=[O:4]>C(OCC)(=O)C>[CH3:12][C:9]1[CH:10]=[CH:11][C:6]([S:3]([OH:5])(=[O:4])=[O:2])=[CH:7][CH:8]=1
8
CCOC(C)=O
null
null
120
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
534,984
CC(C)OC(=O)N=NC(=O)OC(C)C
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
null
ord_dataset-b1a34bc8c1204d51a772ed27396c794e
2002-01-01T00:02:00
true
A solution of methyl 3-(4-hydroxyphenyl)propionate (10.0 g, 55. 5 mmol), N-methyl-N-dodecylethanolamine (13.5 g, 55.5 mmol) and triphenylphosphine (16.0 g, 61.0 mmol) in dry tetrahydrofuran (200 ml) was treated at 22° C. with diisopropyl azodicarboxylate (12.3 g, 61.0 mmol) added dropwise over 50 min. After 3 h at 22° C., the reaction mixture was evaporated under reduced pressure and the residue was triturated with hexane. The solid formed was filtered, washed with hexane and the combined filtrate was chromatographed on silica gel using a gradient of ethyl acetate in hexane (20%-60%) as eluent. Distillation under vacuum then gave 18.0 g (75%) of 3-{4-[2-(N-dodecyl-N-methylamino)ethoxy]phenyl} propanoic acid, methyl ester as a clear oil: b.p. 180-183° C./0.02 torr (bulb to bulb distillation, air bath temperature).
CCCCCCCCCCCCN(C)CCOc1ccc(CCC(=O)OC)cc1
null
COC(=O)CCc1ccc(O)cc1
CCCCCCCCCCCCN(C)CCO
null
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.[CH3:14][N:15]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:16][CH2:17]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH2:19]([N:15]([CH2:16][CH2:17][O:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:6][CH:7]=1)[CH3:14])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
3
C1CCOC1
null
null
null
null
887.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
724,278
null
null
null
null
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
2006-01-01T00:08:00
true
To a stirred solution of (S)-nicotine (0.41 g, 2.5 mmol) in AcOH (10 ml) was added 1-bromo-oct-3-yne (1.16 g, 6.14 mmol). The mixture was heated at reflux for 3 days. AcOH was evaporated and the residue was dissolved in CHCl3. The mixture was washed with saturated aqueous NaHCO3, water and brine successively and dried. Evaporation of the solvent followed by titration with ether afforded 0.50 g (56%) of (S)-3-(1-methyl-pyrrolidin-2-yl)-1-oct-3-ynyl-pyridinium bromide (NONB-3y) as a brown oil. 1H NMR (300 MHz, CDCl3) δ 9.74 (1H, d, J=5.1 Hz), 9.15 (1H, s), 8.43 (1H, d, J=7.8 Hz), 8.04 (1H, dd, J=7.8, 5.1 Hz), 5.13 (2H, m), 3.51 (1H, t, J=7.8 Hz), 3.23 (1H, m), 3.00 (2H, m), 2.42 (2H, m), 2.22 (3H, s), 2.01 (2H, m), 1.89 (2H, m), 1.64 (2H, m), 1.28 (4H, m), 0.82 (3H, t, J=7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 145.97, 144.38, 144.10, 143.57, 128.00, 86.12, 74.07, 67.30, 60.72, 56.92, 40.74, 36.11, 30.94, 23.14, 22.50, 22.16, 18.54, 13.80; Anal. Calcd for C18H27BrN2.0.5H2O: C, 60.00; H, 7.83; N, 7.77. Found: C, 60.15; H, 7.92; N, 6.92.
CCCCC#CCC[n+]1cccc([C@@H]2CCCN2C)c1
[Br-]
CCCCC#CCCBr
CN1CCC[C@H]1c1cccnc1
null
[N:1]1[CH:6]=[C:5]([C@@H:7]2[CH2:12][CH2:11][CH2:10][N:8]2[CH3:9])[CH:4]=[CH:3][CH:2]=1.[Br:13][CH2:14][CH2:15][C:16]#[C:17][CH2:18][CH2:19][CH2:20][CH3:21]>CC(O)=O>[Br-:13].[CH3:9][N:8]1[CH2:10][CH2:11][CH2:12][C@H:7]1[C:5]1[CH:6]=[N+:1]([CH2:14][CH2:15][C:16]#[C:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH:2]=[CH:3][CH:4]=1
null
CC(=O)O
null
null
null
56.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
664,667
CC(=O)[O-]
Cl
[Na+]
null
ord_dataset-5a3d853c53674888a5691dce2e398792
2005-01-01T00:03:00
true
First, 50 g (0.61 mol) of sodium acetate and 41 g (0.14 mol) of 1,1-dibromo-3,3,3-trifluoroacetone were mixed with 500 ml of water, and the mixture was stirred at 80° C. for 30 minutes and then cooled to 0° C. Then, 45 g (0.14 mol) of 4-bromo-2-fluoro-5-isopropoxyphenylhydrazine hydrochloride was added at 10° C. or lower, and the mixture was stirred at 10° C. or lower for 3 hours. The precipitated crystals were collected by filtration and dried, which afforded 35 g (94.3 mmol) of 3,3,3-trifluoro-2-oxopropanal 1-(4-bromo-2-fluoro-5-isopropoxyphenylhydrazone).
CC(C)Oc1cc(NN=CC(=O)C(F)(F)F)c(F)cc1Br
null
O=C(C(Br)Br)C(F)(F)F
CC(C)Oc1cc(NN)c(F)cc1Br
null
C([O-])(=O)C.[Na+].Br[CH:7](Br)[C:8]([C:10]([F:13])([F:12])[F:11])=[O:9].Cl.[Br:16][C:17]1[C:22]([O:23][CH:24]([CH3:26])[CH3:25])=[CH:21][C:20]([NH:27][NH2:28])=[C:19]([F:29])[CH:18]=1>O>[Br:16][C:17]1[C:22]([O:23][CH:24]([CH3:25])[CH3:26])=[CH:21][C:20]([NH:27][N:28]=[CH:7][C:8](=[O:9])[C:10]([F:13])([F:12])[F:11])=[C:19]([F:29])[CH:18]=1
0.5
O
null
null
80
null
67.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
389,894
null
null
null
null
ord_dataset-44d518e567bd4c039d77233023f78bb2
1998-01-01T00:01:00
true
1.8 g (6.2 mmol) N-(2,4-dichlorophenyl)tetrahydro-4H-1,3,4-oxadiazine-4-carbothioamide was dissolved in 30 mL toluene and 1 mL triethylamine in the presence of a small quantity of activated charcoal at 0°-5° C. 3.49 g (6.81 mmol) phosgene as 20% solution in 30 mL toluene was added dropwise over 1.5 h. The reaction mixture was then left to warm up to room temperature and stirred overnight. The activated charcoal was removed by filtration and the solvent evaporated in vacuo. The desired product was isolated after chromatography on silica gel.
O=c1sc(=Nc2ccc(Cl)cc2Cl)n2n1COCC2
null
O=C(Cl)Cl
S=C(Nc1ccc(Cl)cc1Cl)N1CCOCN1
null
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([N:12]1[CH2:17][CH2:16][O:15][CH2:14][NH:13]1)=[S:11].C(N(CC)CC)C.C.[C:26](Cl)(Cl)=[O:27]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]=[C:10]1[N:12]2[N:13]([CH2:14][O:15][CH2:16][CH2:17]2)[C:26](=[O:27])[S:11]1
8
CCN(CC)CC
Cc1ccccc1
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
209,050
null
null
null
null
ord_dataset-ac1c7aa04d6c4e588e723e3e05721681
1990-01-01T00:05:00
true
10-Bromo-1,8-dihydroxy-9-anthrone (3.05 g) was dissolved in dichloromethane (100 ml) and thiophenol (1.1 ml) was added. The red-brown solution became yellow-green, and was then left, with stirring, at room temperature for 5 hours. Removal of the solvent gave a yellow solid which, after recrystallisation from a hexane/chloroform mixture (10:1), afforded 1,8-dihydroxy-10-phenylthio-9-anthrone (2.89 g, 87%) as pale yellow needles, melting point 156°-157° C. (Found: C 71.8, H 4.2, S 9.95; C20H14O3S requires C 71.85, H 4.2, S 9.6%.)
O=C1c2c(O)cccc2C(Sc2ccccc2)c2cccc(O)c21
null
O=C1c2c(O)cccc2C(Br)c2cccc(O)c21
Sc1ccccc1
null
Br[CH:2]1[C:15]2[C:10](=[C:11]([OH:16])[CH:12]=[CH:13][CH:14]=2)[C:9](=[O:17])[C:8]2[C:7]([OH:18])=[CH:6][CH:5]=[CH:4][C:3]1=2.[C:19]1([SH:25])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>ClCCl>[OH:18][C:7]1[C:8]2[C:9](=[O:17])[C:10]3[C:15](=[CH:14][CH:13]=[CH:12][C:11]=3[OH:16])[CH:2]([S:25][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:3]=2[CH:4]=[CH:5][CH:6]=1
5
ClCCl
null
null
25
87
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
234,295
null
null
null
null
ord_dataset-45d20d09e4d64f45bdd419044025b4d3
1991-01-01T00:09:00
true
N.m.r. in solvent A: 4.15 (m, 1H), 4.38 (m, 1H), 4.48 (m, 1H , 4.92 (m, 1H , 6.94 (s, 1H), 7.4 (s, 15H). 9. N.m.r. in solvent C: 3.4 (m, 2H), 4.2 - 4.6 (m, 4H), 4.7 (m, 1H), 5.0 (m, 1H), 5.1 (d, 1H), 5.9 (d, 1H), 6.9 (s, 1H), 7.4 (s, 15H). 10. The starting material was prepared by reaction of 2-bromomethylimidazole with N-hydroxy-phthalimide, deprotection to give 0-(imidazol-2-yl)methylhydroxylamine and condensation with 2-(2-aminothiazol-4-yl)glyoxylic acid to give 2-(2-aminothiazol-4-yl)-2-[(Z)-(imidazol-2-yl)-methoxyimino]acetic acid.
Nc1nc(/C(=N/OCc2ncc[nH]2)C(=O)O)cs1
null
O=C1c2ccccc2C(=O)N1O
BrCc1ncc[nH]1
Nc1nc(C(=O)C(=O)O)cs1
Br[CH2:2][C:3]1[NH:4][CH:5]=[CH:6][N:7]=1.[OH:8][N:9]1C(=O)C2=CC=CC=C2C1=O.[NH2:20][C:21]1[S:22][CH:23]=[C:24]([C:26](=O)[C:27]([OH:29])=[O:28])[N:25]=1>>[NH2:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:9]/[O:8][CH2:2][C:3]2[NH:4][CH:5]=[CH:6][N:7]=2)/[C:27]([OH:29])=[O:28])[N:25]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,709,670
O=C(O)c1ccc(NC(=O)N2Cc3ccccc3C2)cc1
null
null
null
ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb
2016-01-01T00:04:00
true
The title compound was prepared as described in Example 1C, substituting cyclopentylamine for 3-phenylpropan-1-amine and 1-(4-(2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-2-carboxamido)phenyl)azetidine-3-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.59 (s, 1H), 8.49 (d, J=5.0 Hz, 1H), 8.13 (s, 1H), 7.91 (d, J=7.2 Hz, 1H), 7.42 (d, J=5.1 Hz, 1H), 7.34-7.27 (m, 2H), 6.41-6.33 (m, 2H), 4.79-4.73 (m, 4H), 4.06-3.94 (m, 1H), 3.92-3.84 (m, 2H), 3.76-3.66 (m, 2H), 3.46-3.33 (m, 1H), 1.86-1.72 (m, 2H), 1.67-1.30 (m, 6H); MS (ESI(+)) m/e 406 (M+H)+.
O=C(NC1CCCC1)C1CN(c2ccc(NC(=O)N3Cc4ccncc4C3)cc2)C1
null
O=C(O)C1CN(c2ccc(NC(=O)N3Cc4ccncc4C3)cc2)C1
NCCCc1ccccc1
null
[C:1]1([CH2:7][CH2:8][CH2:9][NH2:10])[CH:6]=CC=CC=1.[CH2:11]1[C:19]2[CH:18]=[CH:17][N:16]=[CH:15][C:14]=2[CH2:13][N:12]1[C:20]([NH:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:32][CH:31]([C:33](O)=[O:34])[CH2:30]2)=[CH:25][CH:24]=1)=[O:21].C1C2C(=CC=CC=2)CN1C(NC1C=CC(C(O)=O)=CC=1)=O>>[CH:9]1([NH:10][C:33]([CH:31]2[CH2:30][N:29]([C:26]3[CH:25]=[CH:24][C:23]([NH:22][C:20]([N:12]4[CH2:11][C:19]5[CH:18]=[CH:17][N:16]=[CH:15][C:14]=5[CH2:13]4)=[O:21])=[CH:28][CH:27]=3)[CH2:32]2)=[O:34])[CH2:6][CH2:1][CH2:7][CH2:8]1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,580,583
null
null
null
null
ord_dataset-380e279f82154dba9e08ab51b3bdd08a
2015-01-01T00:05:00
true
To a solution of tert-butyl 2-(5-methoxy-2,3-dioxoindolin-1-yl)acetate (0.65 g, 2.231 mmol) in DCM (20 ml), TFA (2.58 ml, 33.5 mmol) was added. The reaction was stirred at room temperature for 72 hours, then the solvent was evaporated to dryness affording 2-(5-methoxy-2,3-dioxoindolin-1-yl)acetic acid that was used in the next step without further purification (0.48 g, 2.041 mmol, 91% yield). MS/ESI+ 235.9 [MH]+
COc1ccc2c(c1)C(=O)C(=O)N2CC(=O)O
null
COc1ccc2c(c1)C(=O)C(=O)N2CC(=O)OC(C)(C)C
null
null
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]([O:15]C(C)(C)C)=[O:14])[C:7](=[O:20])[C:6]2=[O:21].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]([OH:15])=[O:14])[C:7](=[O:20])[C:6]2=[O:21]
72
ClCCl
O=C(O)C(F)(F)F
null
25
91
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,443,267
[H-]
[Na+]
null
null
ord_dataset-275a3da8f45f4536ad29727f0ef9ba66
2014-01-01T00:06:00
true
To a suspension of (2S,3S,5R)-2-benzyl-3-(5-bromo-pyrimidin-2-ylamino)-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (0.064 mmol; 28.6 mg) and sodium hydride (60% dispersion in mineral oil, 0.19 mmol; 7.6 mg) in DMF (0.6 mL) is added 3-chloro-5-trifluoromethylbenzyl bromide (0.13 mmol; 35.6 mg) at room temperature under N2. After 3.5 hours, additional sodium hydride (60% dispersion in mineral oil, 0.19 mmol; 7.6 mg) is added to the suspension. The reaction mixture is stirred for 20 minutes, and quenched with water and saturated aqueous ammonium chloride solution. The product is extracted three times with EtOAc. The combined organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (eluent: n-hexane/EtOAc) to give (2S,3S,5R)-2-Benzyl-3-[(5-bromo-pyrimidin-2-yl)-(3-chloro-5-trifluoromethyl-benzyl)-amino]-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (30.0 mg, 73%); ESI-MS m/z: 639 [M+1]+, Retention time 2.68 min (condition A).
CC[C@@H]1C[C@H](N(Cc2cc(Cl)cc(C(F)(F)F)c2)c2ncc(Br)cn2)[C@H](Cc2ccccc2)N1C(=O)OC(C)C
null
FC(F)(F)c1cc(Cl)cc(CBr)c1
CC[C@@H]1C[C@H](Nc2ncc(Br)cn2)[C@H](Cc2ccccc2)N1C(=O)OC(C)C
null
[CH:1]([O:4][C:5]([N:7]1[C@H:11]([CH2:12][CH3:13])[CH2:10][C@H:9]([NH:14][C:15]2[N:20]=[CH:19][C:18]([Br:21])=[CH:17][N:16]=2)[C@@H:8]1[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:6])([CH3:3])[CH3:2].[H-].[Na+].[Cl:31][C:32]1[CH:33]=[C:34]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=1)[CH2:35]Br>CN(C=O)C>[CH:1]([O:4][C:5]([N:7]1[C@H:11]([CH2:12][CH3:13])[CH2:10][C@H:9]([N:14]([C:15]2[N:20]=[CH:19][C:18]([Br:21])=[CH:17][N:16]=2)[CH2:35][C:34]2[CH:37]=[C:38]([C:40]([F:41])([F:42])[F:43])[CH:39]=[C:32]([Cl:31])[CH:33]=2)[C@@H:8]1[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:6])([CH3:2])[CH3:3]
3.5
CN(C)C=O
null
null
null
null
73.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,253,968
null
null
null
null
ord_dataset-c544c0c663f54dbea4ddb52ddde7934e
2013-01-01T00:01:00
true
The title compound was prepared under the same conditions as described in Example 112 with 5-(2-dimethylamino-ethyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde and N-(5-fluoro-2-oxo-2,3-dihydro-1H-indol-6-yl)-2-hydroxy-2-methyl-propionamide as starting materials to give N-{3-[5-(2-dimethylamino-ethyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-ylmethylene]-5-fluoro-2-oxo-2,3-dihydro-1H-indol-6-yl}-2-hydroxy-2-methyl-propionamide (40 mg, 41.8%) as a yellow solid.
Cc1c(C=C2C(=O)Nc3cc(NC(=O)C(C)(C)O)c(F)cc32)[nH]c2c1C(=O)N(CCN(C)C)CC2
null
Cc1c(C=O)[nH]c2c1C(=O)N(CCN(C)C)CC2
CC(C)(O)C(=O)Nc1cc2c(cc1F)CC(=O)N2
null
[CH3:1][N:2]([CH3:18])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][C:8]2[NH:11][C:12]([CH:15]=O)=[C:13]([CH3:14])[C:7]=2[C:6]1=[O:17].[F:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][C:28]=1[NH:29][C:30](=[O:35])[C:31]([OH:34])([CH3:33])[CH3:32])[NH:25][C:24](=[O:36])[CH2:23]2>>[CH3:1][N:2]([CH3:18])[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][C:8]2[NH:11][C:12]([CH:15]=[C:23]3[C:22]4[C:26](=[CH:27][C:28]([NH:29][C:30](=[O:35])[C:31]([OH:34])([CH3:32])[CH3:33])=[C:20]([F:19])[CH:21]=4)[NH:25][C:24]3=[O:36])=[C:13]([CH3:14])[C:7]=2[C:6]1=[O:17]
null
null
null
null
null
null
41.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,367,107
O=P([O-])([O-])[O-]
[H-]
[Na+]
null
ord_dataset-d932d1d683704a8bad3d064bcb197acc
2013-01-01T00:11:00
true
The title compound was prepared according to the general procedure as described in method A for the preparation of phosphate derivatives by coupling N-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)acetamide (150 mg, 0.322 mmol) with freshly prepared di-tert-butyl iodomethyl phosphate (Intermediate 2) (395.16 mg, 1.129 mmol) in the presence of sodium hydride (60% dispersion in mineral oil, 20 mg, 0.483 mmol) in dry DMF (2 ml) with to yield 135 mg of pure product as an off-white solid. 1H NMR (300 MHz, CDCl3): δ 1.48 (br s, 18H), 3.35 (s, 3H), 3.47 (s, 2H), 3.62 (s, 3H), 5.71 (s, 2H), 6.36 (br s, 2H), 7.42-7.50 (m, 1H), 7.60-7.72 (m, 1H), 8.02 (s, 1H).
Cn1c(=O)c2c(ncn2CC(=O)N=c2scc(-c3ccc(Cl)c(Cl)c3)n2COP(=O)(OC(C)(C)C)OC(C)(C)C)n(C)c1=O
null
Cn1c(=O)c2c(ncn2CC(=O)Nc2nc(-c3ccc(Cl)c(Cl)c3)cs2)n(C)c1=O
CC(C)(C)OP(=O)(OCI)OC(C)(C)C
null
P([O-])([O-])([O-])=O.[Cl:6][C:7]1[CH:8]=[C:9]([C:14]2[N:15]=[C:16]([NH:19][C:20](=[O:35])[CH2:21][N:22]3[C:30]4[C:29](=[O:31])[N:28]([CH3:32])[C:27](=[O:33])[N:26]([CH3:34])[C:25]=4[N:24]=[CH:23]3)[S:17][CH:18]=2)[CH:10]=[CH:11][C:12]=1[Cl:13].[P:36]([O:48][CH2:49]I)([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37].[H-].[Na+]>CN(C=O)C>[P:36]([O:48][CH2:49][N:15]1[C:14]([C:9]2[CH:10]=[CH:11][C:12]([Cl:13])=[C:7]([Cl:6])[CH:8]=2)=[CH:18][S:17][C:16]1=[N:19][C:20](=[O:35])[CH2:21][N:22]1[C:30]2[C:29](=[O:31])[N:28]([CH3:32])[C:27](=[O:33])[N:26]([CH3:34])[C:25]=2[N:24]=[CH:23]1)([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])([O:43][C:44]([CH3:45])([CH3:46])[CH3:47])=[O:37]
null
CN(C)C=O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
169,002
[BH4-]
[Na+]
null
null
ord_dataset-37d3220f708c49ad839bab296b722248
1988-01-01T00:03:00
true
Use the method of Example 17b, reaction of 2,2-dimethylbenzothiazolidine with sodium borohydride to obtain the title compound.
CC(C)Nc1ccccc1S
null
CC1(C)Nc2ccccc2S1
null
null
[CH3:1][C:2]1([CH3:11])[NH:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[S:3]1.[BH4-].[Na+]>>[CH:2]([NH:6][C:5]1[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=1[SH:3])([CH3:11])[CH3:1]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
14,315
null
null
null
null
ord_dataset-7f88a5da29d74264aae5239be74b3981
1976-01-01T00:10:00
true
4.3 gm (55 millimols) of acetyl chloride were added dropwise to a mixture of 11.8 gm (50 millimols) of 11-chloro-2,3,4,5-tetrahydro-1H-azepino[4,3-b]quinoline, 5.5 gm. (55 millimols) of triethylamine and 300 ml of chloroform. After 100 hours of standing, the mixture was washed with water, and the chloroform phase was evaporated. The raw crystalline base was purified on a silicagel column with benzene/acetone (2:1) as the eluant. The hydrochloride was precipitated from isopropanol with isopropanolic hydrochloric acid.
CC(=O)N1CCCc2nc3ccccc3c(Cl)c2C1
Cl
Clc1c2c(nc3ccccc13)CCCNC2
CC(=O)Cl
null
[C:1]([Cl:4])(=[O:3])[CH3:2].[Cl:5][C:6]1[C:15]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N:9]=[C:8]2[CH2:16][CH2:17][CH2:18][NH:19][CH2:20][C:7]=12.C(N(CC)CC)C>C(Cl)(Cl)Cl>[ClH:4].[C:1]([N:19]1[CH2:18][CH2:17][CH2:16][C:8]2=[N:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=3[C:6]([Cl:5])=[C:7]2[CH2:20]1)(=[O:3])[CH3:2]
100
CCN(CC)CC
ClC(Cl)Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
13,263
[Pd]
Cl
null
null
ord_dataset-a0071d97083e4e69ae8872417ed2776b
1976-01-01T00:09:00
true
A mixture of 6.15 g (0.016 mole) of 2,7--bis(piperidinomethyl)fluorene-9-ol, 12.1 ml of 10% hydrochloric acid, sufficient deionized water to bring the total volume to 150 ml, and 3.0 g of 10% palladium on charcoal catalyst is placed in a Paar hydrogenation apparatus and hydrogenated at room temperature for a period of 2 hours and 45 minutes. The resulting mixture is filtered and sufficient 20% sodium hydroxide solution is added to render the mixture basic to phenolphthalein indicator. The reaction mixture is extracted four times with chloroform, the extracts combined, washed twice with deionized water, treated with charcoal, filtered, and the major portion of the solvent removed at atmospheric pressure. The residue is recrystallized twice from methanol and once again from acetone yielding 2,7-bis(piperidinomethyl)fluorene having a m.p. 135°-6°C, λmax0.1N HCl 270, and E1cm1% 807.
c1cc2c(cc1CN1CCCCC1)Cc1cc(CN3CCCCC3)ccc1-2
null
OC1c2cc(CN3CCCCC3)ccc2-c2ccc(CN3CCCCC3)cc21
null
null
[N:1]1([CH2:7][C:8]2[CH:20]=[CH:19][C:18]3[C:17]4[C:12](=[CH:13][C:14]([CH2:21][N:22]5[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]5)=[CH:15][CH:16]=4)[CH:11](O)[C:10]=3[CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl>[Pd].O>[N:1]1([CH2:7][C:8]2[CH:20]=[CH:19][C:18]3[C:17]4[C:12](=[CH:13][C:14]([CH2:21][N:22]5[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]5)=[CH:15][CH:16]=4)[CH2:11][C:10]=3[CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
0.75
O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
329,020
BrBr
[Na+]
null
null
ord_dataset-2c460e2ef9934444aaf26fec1f75741f
1996-01-01T00:05:00
true
To a solution of NaOH (47.2 g, 1.18 mole) in ice/H2O (270 g) maintained at 4°-5° C. was added Br2 (68.7 g, 0.43 mole) followed by 4-methyl-4-phenyl-2-pentanone (23.7 g, 0.135 mole). The reaction was stirred for 18 hours at room temperature. The crude reaction mixture was extracted with CCl4 (discarded), acidified to pH 1-2 with concentrated HCl solution and extracted with ethyl acetate. The combined organics were washed with saturated NaCl solution, dried over Na2SO4 and evaporated in vacuo to obtain 22.5 g of the title B compound as an off-white solid. This was used in the next step without further purification. MS: (M+NH4)+ @ 196.
CC(C)(CC(=O)O)c1ccccc1
null
CC(=O)CC(C)(C)c1ccccc1
[OH-]
null
[OH-:1].[Na+].BrBr.[CH3:5][C:6]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:11])[CH2:7][C:8](=[O:10])C>>[CH3:11][C:6]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([CH3:5])[CH2:7][C:8]([OH:10])=[O:1]
18
null
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
697,333
null
null
null
null
ord_dataset-4e9c2fa02a7544fd839206719263345f
2006-01-01T00:02:00
true
The title compound, colorless oil, MS: m/e=456.5 (M+H+), was prepared in accordance with the general method of example 82b from (2RS,5RS)-2-(4-chloro-butyl)-5-(4-fluoro-phenyl)-1-(toluene-4-sulfonyl)-pyrrolidine and 4-methyl-1H-imidazole.
Cc1ccc(S(=O)(=O)N2C(CCCCn3cnc(C)c3)CCC2c2ccc(F)cc2)cc1
null
Cc1ccc(S(=O)(=O)N2C(CCCCCl)CCC2c2ccc(F)cc2)cc1
Cc1c[nH]cn1
null
Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[N:7]1[S:18]([C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1)(=[O:20])=[O:19].[CH3:28][C:29]1[N:30]=[CH:31][NH:32][CH:33]=1>>[F:17][C:14]1[CH:15]=[CH:16][C:11]([CH:8]2[N:7]([S:18]([C:21]3[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=3)(=[O:20])=[O:19])[CH:6]([CH2:5][CH2:4][CH2:3][CH2:2][N:32]3[CH:33]=[C:29]([CH3:28])[N:30]=[CH:31]3)[CH2:10][CH2:9]2)=[CH:12][CH:13]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,555,392
null
null
null
null
ord_dataset-4e54080057a44c3887653391e24c90b6
2015-01-01T00:03:00
true
To a solution of N-(5-((2-aminopyridin-4-yl)oxy)pyridin-2-yl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (300 mg, 0.72 mmol) in acetic anhydride (4 mL) was added Et3N (400 mg, 4 mmol), the reaction mixture was stirred at 30° C. for 12 hours and concentrated in vacuo. The residue was purified by a silica gel column chromatography (DCM/CH3OH (v/v)=40/1) to give the title compound as a light yellow solid (197 mg, 60.1%).
CC(=O)Nc1cc(Oc2ccc(NC(=O)c3c(C)n(C)n(-c4ccccc4)c3=O)nc2)ccn1
null
CC(=O)OC(C)=O
Cc1c(C(=O)Nc2ccc(Oc3ccnc(N)c3)cn2)c(=O)n(-c2ccccc2)n1C
null
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16]([C:18]3[C:19](=[O:31])[N:20]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:21]([CH3:24])[C:22]=3[CH3:23])=[O:17])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.CCN(CC)CC.[C:39](OC(=O)C)(=[O:41])[CH3:40]>>[C:39]([NH:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16]([C:18]3[C:19](=[O:31])[N:20]([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[N:21]([CH3:24])[C:22]=3[CH3:23])=[O:17])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1)(=[O:41])[CH3:40]
12
CCN(CC)CC
null
null
30
60.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
729,963
[Li]CCCC
null
null
null
ord_dataset-eb4226b4f7644a01a737e7547b70014a
2006-01-01T00:09:00
true
To a cold (0° C.) solution of diisopropylamine (4.1 mL, 29 mmol) in tetrahydrofuran (25 mL) was added butyllithium (17 mL, 1.6 M in hexanes, 28 mmol) dropwise. The resultant solution was stirred at 0° C. for 10 minutes then cooled to −78° C. The reaction mixture was transferred via syringe to a cold (−78° C.) solution of N-cyclopentyl-4-[2-(4-fluorophenyl)-6-(triethoxymethyl)pyrazolo[1,5-α]pyridin-3-yl]-2-pyrimidinamine (4.86 g, 9.35 mmol) in tetrahydrofuran (25 mL). The reaction mixture was stirred at −78° C. for 30 minutes. Carbon tetrachloride (3.6 mL 37 mmol) was added and the resulting mixture was warmed to room temperature and stirred for 2 hours. The reaction mixture was poured onto ice. After the ice had melted, the aqueous mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over sodium sulfate. Filtration and concentration followed by flash chromatography (4:1 hexanes:ethyl acetate) provided 4-[7-chloro -2-(4-fluorophenyl)-6-(triethoxymethyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-2-pyrimidinamine (2.37 g, 46%) as a yellow solid. Rf 0.36 (4:1 hexanes:ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 8.36 (d, 1H), 8.08 (d, 1H), 7.85 (d, 1H), 7.67 (m, 2H), 7.15 (t, 2H), 6.33 (d, 1H), 5.15 (d, 1H), 4.36 (m, 1H), 3.46 (q, 6H), 2.10 (m, 2H), 1.81–1.53 (m, 6H), 1.26 (t, 9H); MS m/z 554 (M+1).
CCOC(OCC)(OCC)c1ccc2c(-c3ccnc(NC4CCCC4)n3)c(-c3ccc(F)cc3)nn2c1Cl
null
ClC(Cl)(Cl)Cl
CCOC(OCC)(OCC)c1ccc2c(-c3ccnc(NC4CCCC4)n3)c(-c3ccc(F)cc3)nn2c1
null
C(NC(C)C)(C)C.C([Li])CCC.[CH:13]1([NH:18][C:19]2[N:24]=[C:23]([C:25]3[C:26]([C:44]4[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=4)=[N:27][N:28]4[CH:33]=[C:32]([C:34]([O:41][CH2:42][CH3:43])([O:38][CH2:39][CH3:40])[O:35][CH2:36][CH3:37])[CH:31]=[CH:30][C:29]=34)[CH:22]=[CH:21][N:20]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1.C(Cl)(Cl)(Cl)[Cl:52]>O1CCCC1>[Cl:52][C:33]1[N:28]2[N:27]=[C:26]([C:44]3[CH:45]=[CH:46][C:47]([F:50])=[CH:48][CH:49]=3)[C:25]([C:23]3[CH:22]=[CH:21][N:20]=[C:19]([NH:18][CH:13]4[CH2:17][CH2:16][CH2:15][CH2:14]4)[N:24]=3)=[C:29]2[CH:30]=[CH:31][C:32]=1[C:34]([O:41][CH2:42][CH3:43])([O:38][CH2:39][CH3:40])[O:35][CH2:36][CH3:37]
0.5
C1CCOC1
CC(C)NC(C)C
null
-78
null
45.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
134,258
null
null
null
null
ord_dataset-b76b52f4448a4eedb28ffcd8f902046a
1985-01-01T00:09:00
true
Under a nitrogen atmosphere, a stirred suspension of 2-(4-fluorophenyl)-2-(4-methylphenylsulfonyloxy)iminoacetonitrile (64.0 g, 0.2 mole) and triethylamine (61.8 g, 0.61 mole) in 1 l of absolute ethanol was cooled to 5° C. Ethyl 2-mercaptoacetate (26.8 g, 0.22 mole) was added dropwise over a four hour period. The reaction mixture was then stirred for 16 hours and warmed to room temperature. The reaction mixture was concentrated and poured into 2 l of ice water. The resultant precipitate was collected by filtration. The solid filter cake was washed with water and dried. The solid was dissolved in 1.5 l of boiling heptane, and the solution was slurried with silica gel. The hot mixture was filtered; on cooling the filtrate, the solid recrystallized and was collected by filtration, washed with heptane, and dried to give ethyl 3-(4-fluorophenyl)-4-amino-5-isothiazolecarboxylate (22.0 g, mp 137°-139° C.).
CCOC(=O)c1snc(-c2ccc(F)cc2)c1N
null
CCOC(=O)CS
Cc1ccc(S(=O)(=O)ON=C(C#N)c2ccc(F)cc2)cc1
null
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[N:11]OS(C2C=CC(C)=CC=2)(=O)=O)[C:9]#[N:10])=[CH:4][CH:3]=1.C(N(CC)CC)C.[SH:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33]>C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9]([NH2:10])=[C:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[S:30][N:11]=2)=[CH:6][CH:7]=1
16
CCO
CCN(CC)CC
null
5
41.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
860,367
II
N#N
[Mg]
null
ord_dataset-93908aaae836460ebd48d733eccad483
2009-01-01T00:01:00
true
To a dry 100 mL three-necked flask under a flow of N2 containing magnesium turnings (0.595 g; 24.50 mmol) in dry THF (10 mL) at reflux, an activating, small amount of 1-bromo-4-[(4-chlorophenyl) ethynyl] benzene (VIId) (0.39 g; 1.33 mmol) was added in one portion. N2 flow and stirring were stopped. Reaction mixture was heated at reflux for 5 minutes then iodine crystal was added keeping vigorous reflux to start the reaction. The reaction mixture went colourless after 5minutes and reaction mixture turned black-blue after an additional minute. A solution of the remaining amount of 1-bromo-4-[(4-chlorophenyl) ethynyl] benzene (VIId) (6.104 g; 20.93 mmol) in dry THF (35 mL) at 55° C. was added drop wise into the reaction mixture while keeping gentle reflux. Reflux was maintained for 15minutes then temperature was allowed to cool to RT under stirring for 1 h. The reaction mixture was cooled to 3° C. and a solution of dry 1-formyl-piperidine (3.71 mL; 33.40 mmol) in dry THF (10 mL) was added drop wise maintaining temperature at 5° C. The reaction mixture was then allowed to warm to RT and it was stirred overnight. Protocol and work-up was then similar with those described above. Purification was performed by flash chromatography (SiO2) using (cyclohexane 9-ethyl acetate 1). The title compound (m=1.02 g) was obtained as a white solid in a19% yield. Melting point: 164° C.
O=Cc1ccc(C#Cc2ccc(Cl)cc2)cc1
null
Clc1ccc(C#Cc2ccc(Br)cc2)cc1
O=CN1CCCCC1
null
N#N.[Mg].Br[C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)=[CH:7][CH:6]=1.II.[CH:22](N1CCCCC1)=[O:23]>C1COCC1>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([C:12]#[C:11][C:8]2[CH:9]=[CH:10][C:5]([CH:22]=[O:23])=[CH:6][CH:7]=2)=[CH:14][CH:15]=1
0.08
C1CCOC1
null
null
25
null
318.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,357,905
Cl
null
null
null
ord_dataset-d932d1d683704a8bad3d064bcb197acc
2013-01-01T00:11:00
true
The product of step A was subjected to Boc-deprotection with 2 M HCl in diethyl ether following the procedure of example 28, step B. The crude material was purified by flash column chromatography (SiO2, 90:9:1 chloroform/methanol/ammonium hydroxide) then converted to the HCl salt to give 2-(3-chlorophenyl)sulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole hydrochloride (49 mg, 56%, AUC HPLC 95.7%) as an off white solid: mp 208-212° C.; 1H NMR (CD3OD, 300 MHz) δ 8.30 (d, J=1.8 Hz, 1H), 7.86-7.95 (m, 2H), 7.72-7.78 (m, 1H), 7.57-7.63 (m, 2H), 7.49-7.56 (m, 1H), 5.32 (d, J=4.8 Hz, 1H), 4.51-4.58 (m, 1H), 3.72 (s, 3H), 3.43-3.55 (m, 1H), 3.03-3.12 (m, 1H), 2.24-2.52 (m, 3H), 1.90-2.04 (m, 1H); APCI MS m/z 387 [M+H]+
Cn1c2c(c3cc(S(=O)(=O)c4cccc(Cl)c4)ccc31)C1CCC(C2)N1
null
Cn1c2c(c3c(C(=O)OC(C)(C)C)c(S(=O)(=O)c4cccc(Cl)c4)ccc31)C1CCC(C2)N1
null
null
[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([C:11]2[CH:19]=[CH:18][C:17]3[N:16]([CH3:20])[C:15]4[CH2:21][CH:22]5[NH:26][CH:25]([C:14]=4[C:13]=3[C:12]=2C(OC(C)(C)C)=O)[CH2:24][CH2:23]5)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.Cl>C(OCC)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH3:20])[C:15]2[CH2:21][CH:22]4[NH:26][CH:25]([C:14]3=2)[CH2:24][CH2:23]4)(=[O:9])=[O:10])[CH:5]=[CH:6][CH:7]=1
null
CCOCC
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,028,646
O=C([O-])[O-]
[K+]
null
null
ord_dataset-83acb82dc5ba4f7aba439b9875aaac43
2011-01-01T00:02:00
true
To a mixture of 2-amino-5-bromopyridin-3-ol (0.500 g, 2.64 mmol) and K2CO3 (1.09 g, 7.93 mmol) in acetone (11.0 mL) was added ethyl bromoisobutyrate (0.50 mL, 3.4 mmol). The solution was stirred under N2 for 18 h and then heated to reflux. After 18 h, the solution was cooled and concentrated. The light-pink, sweet-smelling solid was dissolved in CH2Cl2 (50 mL) and MeOH (5 mL). The solution was diluted with H2O (150 mL) and then washed with CH2Cl2 (3×75 mL). The combined organic layers were washed with brine (2×100 mL), dried (Na2SO4) and concentrated to yield the title compound (0.57 g, 84%) as an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ 11.39 (s, 1H), 8.03 (d, J=1.2 Hz, 1H), 7.66 (d, 0.9 Hz, 1H), 1.43 (s, 6H).
CC1(C)Oc2cc(Br)cnc2NC1=O
null
Nc1ncc(Br)cc1O
CCOC(=O)C(C)(C)Br
null
[NH2:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([Br:9])=[CH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].Br[C:17]([CH3:24])([CH3:23])[C:18](OCC)=[O:19]>CC(C)=O>[Br:9][C:5]1[CH:4]=[N:3][C:2]2[NH:1][C:18](=[O:19])[C:17]([CH3:24])([CH3:23])[O:8][C:7]=2[CH:6]=1
18
CC(C)=O
null
null
null
84
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,064,734
null
null
null
null
ord_dataset-ffbef48837674f39816de887b5dc8bae
2011-01-01T00:06:00
true
A mixture of benzhydrylamine (25 g, 136.4 mmol) and trimethylsilylmethyl chloride (8.39 g, 68.4 mmol) in acetonitrile (105 ml) was refluxed overnight. Then the mixture was concentrated under vacuum at 70° C. with a rotary evaporator to remove all volatiles. The white residue was mixed with n-heptane (150 ml) and filtered over a glass filter. The salt residue was washed with n-heptane (2×25 ml). The combined heptane filtrates were concentrated under vacuum to give the crude product as a clear, slightly yellow oil (23 g; >100%). Purification by chromatography on silica gel (700 ml) eluting with n-heptane (2000 ml), followed by n-heptane:ethyl acetate (10:1) gave pure diphenyl-N-((trimethylsilyl)methyl)methanamine (5.5 g, 20.4 mmol; 30%).
C[Si](C)(C)CNC(c1ccccc1)c1ccccc1
null
NC(c1ccccc1)c1ccccc1
C[Si](C)(C)CCl
null
[CH:1]([NH2:14])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15][Si:16]([CH2:19]Cl)([CH3:18])[CH3:17]>C(#N)C>[C:2]1([CH:1]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
null
CC#N
null
null
null
29.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
964,491
O=C([O-])[O-]
[K+]
null
null
ord_dataset-03ba810b7f464a06b5d8787af2e8b64e
2010-01-01T00:06:00
true
N-benzylglycine ethyl ester (1.87 ml) and 5-bromovaleric acid ethyl ester (1.92 ml) are dissolved in dimethylformamide (100 ml) and stirred in the presence of potassium carbonate (1.66 g) for 2 days at room temperature. The reaction is quenched with saturated aqueous ammonium chloride solution, and extraction is carried out with ethyl acetate. After drying over sodium sulphate the combined organic phases are concentrated by evaporation. From the obtained residue, 5-(benzyl-ethoxycarbonylmethyl-amino)-pentanoic acid is isolated in a yield of 30% by chromatography using silica gel (ethyl acetate/heptane 1:5).
CCOC(=O)CN(CCCCC(=O)O)Cc1ccccc1
null
CCOC(=O)CNCc1ccccc1
CCOC(=O)CCCCBr
null
[CH2:1]([O:3][C:4](=[O:14])[CH2:5][NH:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:2].C([O:17][C:18](=[O:24])[CH2:19][CH2:20][CH2:21][CH2:22]Br)C.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:7]([N:6]([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:14])[CH2:22][CH2:21][CH2:20][CH2:19][C:18]([OH:24])=[O:17])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
null
CN(C)C=O
null
null
null
null
30
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,040,975
[H-]
[Na+]
[OH-]
null
ord_dataset-3af92aec23dc4810b92eb0d8c60023ee
2011-01-01T00:03:00
true
287 mg (1.2 mmol) of 4-Cyano-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid ethyl ester was dissolved in 2 ml of DMF and 51.1 mg (1.3 mmol) of sodium hydride (60% in mineral oil) were added at RT. After stirring for 20 min at room temperature the solution was cooled to −70° C. and 355 mg (1.3 mmol) of 3-bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole were added. The reaction was stirred at room temperature for 3 h. The reaction solution was treated with 1 ml of 2N aqueous NaOH for 16 h at room temperature. The product was purified by preparative RP-HPLC eluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid). After lyophilization the product was obtained as a white solid.
N#Cc1c(-c2cccs2)nn(Cc2cc(-c3ccc(Cl)s3)on2)c1C(=O)O
null
Clc1ccc(-c2cc(CBr)no2)s1
CCOC(=O)c1[nH]nc(-c2cccs2)c1C#N
null
C([O:3][C:4]([C:6]1[NH:7][N:8]=[C:9]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)[C:10]=1[C:11]#[N:12])=[O:5])C.[H-].[Na+].Br[CH2:21][C:22]1[CH:26]=[C:25]([C:27]2[S:28][C:29]([Cl:32])=[CH:30][CH:31]=2)[O:24][N:23]=1.[OH-].[Na+]>CN(C=O)C>[Cl:32][C:29]1[S:28][C:27]([C:25]2[O:24][N:23]=[C:22]([CH2:21][N:7]3[C:6]([C:4]([OH:3])=[O:5])=[C:10]([C:11]#[N:12])[C:9]([C:13]4[S:14][CH:15]=[CH:16][CH:17]=4)=[N:8]3)[CH:26]=2)=[CH:31][CH:30]=1
0.33
CN(C)C=O
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
538,128
CC(=O)[O-]
O=C([O-])O
[Na+]
null
ord_dataset-1884c7bf3d544afdb8d17b5d41b90a27
2002-01-01T00:03:00
true
A mixture of 6-tert-butoxycarbonylaminothionicotinamide (506 mg), ethyl 2-chloro-acetoacetate (492 mg) and sodium acetate (252 mg) in ethanol (20 ml) was heated for 2 hours under reflux, and to the mixture were added sodium hydrogen carbonate aqueous solution and water. The precipitated crystals were collected by filtration, and the crystals were successively washed with water, ethanol and ether to give ethyl 2-(6-tert-butoxycarbonylamino-3-pyridyl)-4-methyl-5-thiazolecarboxylate (200 mg).
CCOC(=O)c1sc(-c2ccc(NC(=O)OC(C)(C)C)nc2)nc1C
null
CC(C)(C)OC(=O)Nc1ccc(C(N)=S)cn1
CCOC(=O)C(Cl)C(C)=O
null
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([NH2:15])=[S:14])=[CH:11][N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[CH:19]([C:25]([CH3:27])=O)[C:20]([O:22][CH2:23][CH3:24])=[O:21].C([O-])(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(O)C.O>[C:1]([O:5][C:6]([NH:8][C:9]1[N:10]=[CH:11][C:12]([C:13]2[S:14][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:25]([CH3:27])[N:15]=2)=[CH:16][CH:17]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
null
CCO
O
null
null
null
27.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,399,716
O=C([O-])[O-]
[K+]
null
null
ord_dataset-12dc3bd21bcf44d09e5b4249afe15161
2014-01-01T00:02:00
true
{5-[(3-chloropyrazin-2-yl)(hydroxyimino)methyl]-2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-3,4-difluorophenyl}methanol (Intermediate 198, 106 mg, 0.26 mmol) in MeCN (4 mL) was treated with K2CO3 (53.2 mg, 0.39 mmol) at 120° C. for 1 hr. The mixture was diluted with EtOAc and washed with water and brine. The EtOAc solution was dried over anhydrous sodium sulfate, filtered and concentrated to afford 90 mg of product.
C[C@@H]1CN(c2c(CO)cc3c(-c4nccnc4Cl)noc3c2F)C[C@H](C)O1
null
C[C@@H]1CN(c2c(CO)cc(C(=NO)c3nccnc3Cl)c(F)c2F)C[C@H](C)O1
null
null
[Cl:1][C:2]1[C:3]([C:8](=[N:27][OH:28])[C:9]2[C:10](F)=[C:11]([F:25])[C:12]([N:17]3[CH2:22][C@H:21]([CH3:23])[O:20][C@H:19]([CH3:24])[CH2:18]3)=[C:13]([CH2:15][OH:16])[CH:14]=2)=[N:4][CH:5]=[CH:6][N:7]=1.C([O-])([O-])=O.[K+].[K+]>CC#N.CCOC(C)=O>[Cl:1][C:2]1[C:3]([C:8]2[C:9]3[CH:14]=[C:13]([CH2:15][OH:16])[C:12]([N:17]4[CH2:22][C@H:21]([CH3:23])[O:20][C@H:19]([CH3:24])[CH2:18]4)=[C:11]([F:25])[C:10]=3[O:28][N:27]=2)=[N:4][CH:5]=[CH:6][N:7]=1
null
CC#N
CCOC(C)=O
null
null
88.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
726,233
null
null
null
null
ord_dataset-0387783899c642a8b7eb4ba379bcdf5d
2006-01-01T00:08:00
true
A mixture of 3-(2,4-dichloro-pyrimidin-5-yl)-2-(3,5-dimethoxy-phenyl)-propionic acid methyl ester (186 mg, 0.50 mmol) (from Example 3b supra) and aniline (2.0 mL) (Aldrich) was heated at 110° C. for 2 hours. The reaction mixture was washed with hexanes (50 mL×3) and the supernatant was decanted off after each time. The residue was dissolved in ethyl acetate (100 mL) and successively washed with saturated aqueous ammonium chloride solution (30 mL), water (30 mL) and brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give the crude 3-(2,4-diphenylamino-pyrimidin-5-yl)-2-(3,5-dimethoxy-phenyl)-propionic acid methyl ester as an off-white solid which was used in the next step without further purification. (Yield 241.5 mg, 99.7%).
COC(=O)C(Cc1cnc(Nc2ccccc2)nc1Nc1ccccc1)c1cc(OC)cc(OC)c1
null
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1cc(OC)cc(OC)c1
Nc1ccccc1
null
[CH3:1][O:2][C:3](=[O:24])[CH:4]([C:14]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[C:16]([O:22][CH3:23])[CH:15]=1)[CH2:5][C:6]1[C:7](Cl)=[N:8][C:9](Cl)=[N:10][CH:11]=1.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[CH3:1][O:2][C:3](=[O:24])[CH:4]([C:14]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[C:16]([O:22][CH3:23])[CH:15]=1)[CH2:5][C:6]1[C:7]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:8][C:9]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:10][CH:11]=1
null
null
null
null
110
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
481,522
Cl
[Li]O
null
null
ord_dataset-21c1b1c06c7e4e09a38b5b1c71a32e52
2000-01-01T00:10:00
true
A solution of 25 mg (0.6 mmol) of LiOH.H2O in 0.4 ml of H2O is added dropwise to a suspension of 95 mg (0.30 mmol) of 4-(3-chloro-anilino)-6-ethoxycarbonyl-7H-pyrrolo[2,3-d]pyrimidine in 0.7 ml of methanol. The reaction mixture is heated at boiling for 4.5 hours, then cooled in an ice-bath and acidified with 0.6 ml of 1 N HCl solution. Filtering and washing with water yield the title compound; HPLC: tRet (Grad20)=8.7; FAB-MS: (M+H)+ =289.
O=C(O)c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1
null
CCOC(=O)c1cc2c(Nc3cccc(Cl)c3)ncnc2[nH]1
null
null
O[Li].O.[Cl:4][C:5]1[CH:6]=[C:7]([CH:23]=[CH:24][CH:25]=1)[NH:8][C:9]1[C:10]2[CH:17]=[C:16]([C:18]([O:20]CC)=[O:19])[NH:15][C:11]=2[N:12]=[CH:13][N:14]=1.Cl>O.CO>[C:18]([C:16]1[NH:15][C:11]2[N:12]=[CH:13][N:14]=[C:9]([NH:8][C:7]3[CH:23]=[CH:24][CH:25]=[C:5]([Cl:4])[CH:6]=3)[C:10]=2[CH:17]=1)([OH:20])=[O:19]
4.5
O
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
538,604
[K+]
null
null
null
ord_dataset-1884c7bf3d544afdb8d17b5d41b90a27
2002-01-01T00:03:00
true
A solution of Oxone (0.356 g. 0.579 mM) in water (2.5 ml) was added to a stirred suspension of the title product from Example 37 (0.117 g. 0.276 mM) in EtOH (10 ml) and the mixture heated at gentle reflux for 2.75 hours. The mixture was allowed to cool. The solid which precipitated was filtered, washed with water and ether to give the title compound (0.1 09 g). MS: 457 (MH+); NMR(250 MHz) 1.83 (3H, s); 3.38 (3H, s); 3.45 (2H, t); 3.85 (1H, m); 4.23 (1H, t); 4.79 (1H, m); 7.78 (2H, d); 8.0 (2H, d); 8.08 (2H, m); 8.24 (1H, t); 8.48 (1H, s); 10.01 (1H, s).
CC(=O)NC[C@H]1CN(c2ccc(C(=O)c3cnc4ccc(S(C)(=O)=O)cn34)cc2)C(=O)O1
null
CSc1ccc2ncc(C(=O)c3ccc(N4C[C@H](CNC(C)=O)OC4=O)cc3)n2c1
O
O=S([O-])OO
[OH:1]OS([O-])=O.[K+].[CH3:7][S:8][C:9]1[CH:10]=[CH:11][C:12]2[N:13]([C:15]([C:18]([C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:30][C@H:29]([CH2:31][NH:32][C:33](=[O:35])[CH3:34])[O:28][C:27]4=[O:36])=[CH:22][CH:21]=3)=[O:19])=[CH:16][N:17]=2)[CH:14]=1.[OH2:37]>CCO>[CH3:7][S:8]([C:9]1[CH:10]=[CH:11][C:12]2[N:13]([C:15]([C:18]([C:20]3[CH:21]=[CH:22][C:23]([N:26]4[CH2:30][C@H:29]([CH2:31][NH:32][C:33](=[O:35])[CH3:34])[O:28][C:27]4=[O:36])=[CH:24][CH:25]=3)=[O:19])=[CH:16][N:17]=2)[CH:14]=1)(=[O:1])=[O:37]
null
CCO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,616,916
null
null
null
null
ord_dataset-35c51552812941cda45194a013d34bb9
2015-01-01T00:08:00
true
A mixture of 6-bromo-9H-purine (13 mg, 0.065 mmol), 3′-(1-aminoethyl)-5′-chloro-3-fluoro-2′-methoxy-6′-methylbiphenyl-4-carboxamide (20 mg, 0.06 mmol), and N,N-diisopropylethylamine (0.021 mL, 0.12 mmol) in isopropyl alcohol (0.2 mL) was heated at 90° C. under nitrogen overnight. The mixture was evaporated and the resulting mixture was purified on RP-HPLC (XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.2% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product. LCMS calculated for C22H21ClFN6O2 (M+H)+: m/z=455.1. found: 455.0.
COc1c(C(C)Nc2ncnc3[nH]cnc23)cc(Cl)c(C)c1-c1ccc(C(N)=O)c(F)c1
null
COc1c(C(C)N)cc(Cl)c(C)c1-c1ccc(C(N)=O)c(F)c1
Brc1ncnc2[nH]cnc12
null
Br[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][NH:6]2.[NH2:11][CH:12]([C:14]1[C:15]([O:32][CH3:33])=[C:16]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([NH2:30])=[O:29])=[C:24]([F:31])[CH:23]=2)[C:17]([CH3:21])=[C:18]([Cl:20])[CH:19]=1)[CH3:13].C(N(CC)C(C)C)(C)C>C(O)(C)C>[Cl:20][C:18]1[C:17]([CH3:21])=[C:16]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([NH2:30])=[O:29])=[C:24]([F:31])[CH:23]=2)[C:15]([O:32][CH3:33])=[C:14]([CH:12]([NH:11][C:2]2[N:10]=[CH:9][N:8]=[C:7]3[C:3]=2[N:4]=[CH:5][NH:6]3)[CH3:13])[CH:19]=1
null
CCN(C(C)C)C(C)C
CC(C)O
null
90
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
245,243
NCCC(=O)O
null
null
null
ord_dataset-5eb2900a93c842ee98f26c305e657b61
1992-01-01T00:04:00
true
6-Aminocaproic acid is reacted with 3-benzyloxy-2-methyl-4-pyrone in an exactly analogous procedure to that described in Example 2 for the reaction of the latter compound with β-alanine to give 3-benzyloxy-1-(5'-carboxypentyl)-2-methylpyrid-4-one in 70% yield, this compound being obtained after recrystallisation from ethanol/acetone (1:1 v/v) as white crystals, m.p. 145°-147° C.
Cc1c(OCc2ccccc2)c(=O)ccn1CCCCCC(=O)O
null
NCCCCCC(=O)O
Cc1occc(=O)c1OCc1ccccc1
null
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([OH:9])=[O:8].[CH2:10]([O:17][C:18]1[C:23](=[O:24])[CH:22]=[CH:21]O[C:19]=1[CH3:25])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.NCCC(O)=O>>[CH2:10]([O:17][C:18]1[C:23](=[O:24])[CH:22]=[CH:21][N:1]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([OH:9])=[O:8])[C:19]=1[CH3:25])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
null
null
null
null
null
70
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,394,002
null
null
null
null
ord_dataset-12dc3bd21bcf44d09e5b4249afe15161
2014-01-01T00:02:00
true
To a solution of D-Alanine methylester (1.33 g, 12.9 mmol) in acetonitrile (15 mL was added 1,3-propane sultone (1.42 g, 11.7 mmol). The solution was stirred at reflux for 2 hours. The reaction mixture was cooled to room temperature. The solid material was filtered and washed with acetonitrile (2×15 mL). The solid was dissolved in water (30 mL). Dowex Marathon C ion exchange resin (strongly acidic) was added to the solution. The suspension was stirred for 15 minutes before the resin was removed by filtration. The filtrate was evaporated under reduced pressure and dried in vacuo, affording the title compound (1.52 g, 42%). 1H NMR (D2O, 500 MHz) δ ppm 4.07 (m, 1H), 3.72 (s, 3H), 3.14 (m, 2H), 2.89 (t, 2H, J=7.3 Hz), 2.03 (m, 2H), 1.46 (dd, 3H, J=1.95 Hz, 7.3 Hz). 13C (DMSO, 125 MHz) δ ppm 170.74, 55.62, 53.82, 47.96, 44.76, 21.53, 14.03. [α]D=+1.4° (c=0.0088 in water), ES-MS 224 (M−1).
COC(=O)[C@@H](C)NCCCS(=O)(=O)O
null
COC(=O)[C@@H](C)N
O=S1(=O)CCCO1
null
[CH3:1][O:2][C:3](=[O:7])[C@@H:4]([CH3:6])[NH2:5].[CH2:8]1[CH2:14][S:11](=[O:13])(=[O:12])[O:10][CH2:9]1>C(#N)C>[CH3:1][O:2][C:3](=[O:7])[C@H:4]([NH:5][CH2:9][CH2:8][CH2:14][S:11]([OH:13])(=[O:12])=[O:10])[CH3:6]
null
CC#N
null
null
25
57.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
705,639
null
null
null
null
ord_dataset-c408dfed796e4354b61e312e67f7143f
2006-01-01T00:04:00
true
Into a 100 mL single-neck flask, 49 mg of acetyl chloride was added dropwise to 200 mg of {2-[4-(3-aminophenyl)phenyl]-2-fluoropropyl}[(methylethyl)sulfonyl]amine (prepared in example 5) and 63 mg of triethylamine in THF (25 mL) while stirring under a nitrogen atmosphere at room temperature. The reaction was allowed to stir at this temperature for 2 h. The mixture was then poured into H2O and the desired product was extracted into ethyl acetate. The organic layer was backwashed once with H2O, dried over K2CO3, and concentrated under reduced vacuum to yield 193 mg as a foam. This material was purified via silica gel chromatography employing the Chromatotron, using a 4000 micron rotor and eluting with a solvent of hexane/ethyl acetate 1:1 to yield the title compound (121 mg, 54%) as a white foam. Ion spray M.S. 391.2 (M*−1).
CC(=O)Nc1cccc(-c2ccc(C(C)(F)CNS(=O)(=O)C(C)C)cc2)c1
null
CC(=O)Cl
CC(C)S(=O)(=O)NCC(C)(F)c1ccc(-c2cccc(N)c2)cc1
null
[C:1](Cl)(=[O:3])[CH3:2].[NH2:5][C:6]1[CH:7]=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:28])([CH3:27])[CH2:19][NH:20][S:21]([CH:24]([CH3:26])[CH3:25])(=[O:23])=[O:22])=[CH:14][CH:13]=2)[CH:9]=[CH:10][CH:11]=1.C(N(CC)CC)C.O>C1COCC1>[F:28][C:18]([C:15]1[CH:16]=[CH:17][C:12]([C:8]2[CH:7]=[C:6]([NH:5][C:1](=[O:3])[CH3:2])[CH:11]=[CH:10][CH:9]=2)=[CH:13][CH:14]=1)([CH3:27])[CH2:19][NH:20][S:21]([CH:24]([CH3:25])[CH3:26])(=[O:23])=[O:22]
null
C1CCOC1
O
CCN(CC)CC
25
null
54
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
815,398
[Li]CCCC
null
null
null
ord_dataset-50f99930fc41474db226bc80774b38df
2008-01-01T00:04:00
true
nBuLi (2.8 N, 1.01 g, 0.0157 mol) was added at −78° C. to a solution of 1-benzyl-1-(2-hydroxy-ethyl)-3-methyl-urea (3 g, 0.0143 mol, from (i) above) in 30 ml of dry TBF and stirred at same temperature for 30 min under nitrogen atmosphere. P-Toluenesulfonyl chloride (3 g, 0.0157 mol) in 20 ml of dry THF was added dropwise at −78° C. and stirred for 3 h under nitrogen atmosphere. The reaction was quenched with methanol and solvent evaporated under reduced pressure. The crude was purified by column chromatography over silica gel using 12% methanol in dichloromethane as eluent to yield 2.5 g of the title compound as a solid.
CNC(=O)N(CCOS(=O)(=O)c1ccc(C)cc1)Cc1ccccc1
null
Cc1ccc(S(=O)(=O)Cl)cc1
CNC(=O)N(CCO)Cc1ccccc1
null
[Li]CCCC.[CH2:6]([N:13]([CH2:18][CH2:19][OH:20])[C:14]([NH:16][CH3:17])=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:21][C:22]1[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1>C1COCC1>[CH2:6]([N:13]([CH2:18][CH2:19][O:20][S:28]([C:25]1[CH:26]=[CH:27][C:22]([CH3:21])=[CH:23][CH:24]=1)(=[O:30])=[O:29])[C:14]([NH:16][CH3:17])=[O:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
0.5
C1CCOC1
null
null
null
null
48.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
239,424
null
null
null
null
ord_dataset-960c6b9c4fc74afd90a3ebf713215626
1991-01-01T00:12:00
true
A solution of 1,1-dioxo-5-N-formyl-2,3,4,5-tetrahydro-[1,5]-benzothiazepin-3-one (0.410 g, 1.71 mmole) from Example 16, 2,3-dichlorobenzaldehyde (0.297 g, 1.71 mmole) and ethyl 3-aminocrotonate (0.219 g, 1.71 mmole) in 7 mL of ethanol was heated to reflux for 18 hours. The solvent was removed under reduced pressure and the residue was chromatographed (silica gel, 1:1 hexane:ethyl acetate) to obtain the product as an oil (0.75 g, 86% yield). The product was recrystallized from chloroform-ether.
CCOC(=O)C1=C(C)NC2=C(C1c1cccc(Cl)c1Cl)S(=O)(=O)c1ccccc1N(C=O)C2
null
O=Cc1cccc(Cl)c1Cl
O=CN1CC(=O)CS(=O)(=O)c2ccccc21
CCOC(=O)/C=C(/C)N
[O:1]=[S:2]1(=[O:16])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([CH:13]=[O:14])[CH2:5][C:4](=O)[CH2:3]1.[Cl:17][C:18]1[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:19]=1[CH:20]=O.[NH2:27]/[C:28](/[CH3:35])=[CH:29]\[C:30]([O:32][CH2:33][CH3:34])=[O:31]>C(O)C>[Cl:17][C:18]1[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:19]=1[CH:20]1[C:3]2[S:2](=[O:16])(=[O:1])[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[N:6]([CH:13]=[O:14])[CH2:5][C:4]=2[NH:27][C:28]([CH3:35])=[C:29]1[C:30]([O:32][CH2:33][CH3:34])=[O:31]
null
CCO
null
null
null
null
86.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,405,155
O=N[O-]
O=S(=O)(O)O
[Na+]
null
ord_dataset-7456bda2326f4bebaa874a5474d4cc0d
2014-01-01T00:03:00
true
Sodium nitrite (106.1 mg, 1.537 mmol) was dissolved at 0° C. in 1.84 ml of conc. sulfuric acid. Subsequently, [5-(5-aminopyridin-2-yl)-3,4,5,6-tetrahydro-1H-pyrrolo[3,4-c]pyrrol-2-yl](2-trifluoromethylphenyl)methanone acetate (523 mg, 1.2 mmol), dissolved in 8 ml of acetic acid, was added dropwise, the cooling bath was removed and stirring was continued for 1 h. The reaction solution was added dropwise to 50 ml of boiling water and stirred under reflux for 5 h. After cooling, the mixture was admixed with ethyl acetate and filtered off from the residue, the water phase was adjusted to pH 4 with sodium hydrogencarbonate solution, and the organic phase was removed and concentrated. Yield: 181 mg (40%), M+H+: 376.11.
O=C(c1ccccc1C(F)(F)F)N1CC2=C(C1)CN(c1ccc(O)cn1)C2
null
Nc1ccc(N2CC3=C(CN(C(=O)c4ccccc4C(F)(F)F)C3)C2)nc1
CC(=O)O
null
N([O-])=O.[Na+].C(O)(=[O:7])C.N[C:10]1[CH:11]=[CH:12][C:13]([N:16]2[CH2:20][C:19]3[CH2:21][N:22]([C:24]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[C:32]([F:35])([F:34])[F:33])=[O:25])[CH2:23][C:18]=3[CH2:17]2)=[N:14][CH:15]=1>S(=O)(=O)(O)O.C(O)(=O)C>[OH:7][C:10]1[CH:11]=[CH:12][C:13]([N:16]2[CH2:20][C:19]3[CH2:21][N:22]([C:24]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[C:32]([F:35])([F:34])[F:33])=[O:25])[CH2:23][C:18]=3[CH2:17]2)=[N:14][CH:15]=1
1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
888,114
O=C([O-])[O-]
[K+]
null
null
ord_dataset-d728a2f811c0424cbcdb5a84d02b93ae
2009-01-01T00:06:00
true
Using General Procedure A: A suspension of 3,3″-dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-cis-[2,2′;6′,2″]terpyridine (252 mg, 0.94 mmol), methanesulfonic acid 2-pyridin-2-yl-ethyl ester (approx. 4.9 mmol) and K2CO3 (1.30 g, 9.42 mmol) in DMF (5 mL) was heated at 85° C. for 2.5 d. Purification of the crude material by column chromatography on silica gel (CH2Cl2—CH3OH—NH4OH, 96:4:0 then 94:4:2) followed by radial chromatography on silica gel (1 mm plate, CH2Cl2—CH3OH—NH4OH, 25:1:1) provided 152 mg (43%) of COMPOUND 97 as a pale yellow oil. 1H NMR (CDCl3) δ 1.60-1.72 (m, 3H), 1.96-2.23 (m, 5H), 2.51 (s, 6H), 2.61-2.66 (m, 2H), 4.15 (d, 2H, J=12 Hz), 6.33-6.38 (m, 1H), 6.85 (dd, 1H, J=7.2, 5.1 Hz), 7.07 (dd, 2H, J=7.5, 4.8 Hz), 7.27 (dt, 1H, J=7.5, 1.5 Hz), 7.40 (d, 2H, J=7.5 Hz), 8.19 (d, 1H, J=4.8 hz), 8.42-8.47 (m, 2H); 13C NMR (CDCl3) δ 19.18, 25.52, 30.76, 34.77, 49.87, 63.61, 120.80, 122.22, 122.76, 131.72, 136.15, 138.83, 147.10, 149.18, 160.47, 161.42; ES-MS m/z 373 (M+H). Anal. Calcd. for C24H28N4.1.6 H2O: C, 71.83; H, 7.84; N, 13.96. Found: C, 71.84; H, 7.53; N, 13.65.
Cc1cccnc1[C@H]1CCC[C@@H](c2ncccc2C)N1CCc1ccccn1
null
CS(=O)(=O)OCCc1ccccn1
Cc1cccnc1[C@@H]1CCC[C@H](c2ncccc2C)N1
null
[CH3:1][C:2]1[C:3]([C@H:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=3)[NH:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH2:27][CH2:28]OS(C)(=O)=O.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:1][C:2]1[C:3]([C@H:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=3)[N:9]2[CH2:28][CH2:27][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][N:21]=2)=[N:4][CH:5]=[CH:6][CH:7]=1
null
CN(C)C=O
null
null
85
null
43.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
628,089
[BH4-]
[Na+]
null
null
ord_dataset-0a66204fc43e49c2922e6f9107e6b62f
2004-01-01T00:03:00
true
Treatment of 5-(benzyloxy)quinoline-6-carbaldehyde with sodium borohydride in methanol following the procedure described for Example 4, step 1 provides [5-(benzyloxy)quinolin-6-yl]methanol.
OCc1ccc2ncccc2c1OCc1ccccc1
null
O=Cc1ccc2ncccc2c1OCc1ccccc1
null
null
[CH2:1]([O:8][C:9]1[C:18]([CH:19]=[O:20])=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[CH:12][CH:13]=[N:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>CO>[CH2:1]([O:8][C:9]1[C:18]([CH2:19][OH:20])=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[CH:12][CH:13]=[N:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
null
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,025,772
null
null
null
null
ord_dataset-136cfada6ce247b4919085a57363459e
2011-01-01T00:01:00
true
4-[(3-bromophenyl)hydrazono]-4H-pyrazole-3,5-diamine was prepared using 125 mg (0.5 mmol) of 2-[(3-bromophenyl)hydrazono]malononitrile, which was derived from 3-bromoaniline (172 mg, 1.0 mmol) and malononitrile (1.5 mmol), and hydrazine hydrate. The hydrazine hydrate was added to the solution at a temperature of 75° C. despite the fact that the starting material had not fully dissolved. The solution cleared briefly and then a precipitate formed. The resulting solid was isolated by filtration, washed with ethanol, and dried to yield 93 mg (66%) of the compound as an orange solid; 1H NMR (ppm, DMSO-d6): 6.2 (br s, 4H), 7.21-7.32 (m, 2H), 7.50-7.62 (m, 1H), 7.90 (s, 1H), 10.71 (s, 1H).
NC1=NN=C(N)C1=NNc1cccc(Br)c1
null
NN
N#CC(C#N)=NNc1cccc(Br)c1
Nc1cccc(Br)c1
BrC1C=C(N[N:9]=[C:10]([C:13]#[N:14])[C:11]#[N:12])C=CC=1.[Br:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].C(#N)CC#N.O.[NH2:29][NH2:30]>>[Br:15][C:16]1[CH:17]=[C:18]([NH:19][N:9]=[C:10]2[C:11]([NH2:12])=[N:30][N:29]=[C:13]2[NH2:14])[CH:20]=[CH:21][CH:22]=1
null
O
N#CCC#N
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
106,297
null
null
null
null
ord_dataset-64bb36b111c249e0afcce8c5ad9cdbd0
1983-01-01T00:07:00
true
A mixture of 10 g of 6-chloro-7,8,9,10-tetrahydroimidazo[2,1-a]phthalazine and 20.9 g of morpholine was heated at reflux for 72 hours. The mixture was then poured into about 200 ml of ice water and a solid formed immediately. This was separated by filtration and air-dried to give 6-(4-morpholinyl)-7,8,9,10-tetrahydroimidazo[2,1-a]phthalazine melting at about 160°-161° C. This compound has the following structural formula ##STR3##
c1cn2nc(N3CCOCC3)c3c(c2n1)CCCC3
null
Clc1nn2ccnc2c2c1CCCC2
C1COCCN1
null
Cl[C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[C:5]2=[N:12][CH:13]=[CH:14][N:4]2[N:3]=1.[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1>>[N:15]1([C:2]2[C:11]3[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=3[C:5]3=[N:12][CH:13]=[CH:14][N:4]3[N:3]=2)[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1
null
null
null
null
0
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,291,609
null
null
null
null
ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c
2013-01-01T00:05:00
true
By following a procedure analogous to Example 3 starting from 2-bromo-4-methylaniline and 6-benzothiazolesulfonyl chloride, the expected product is obtained in the form of an orange solid (yield=76%).
Cc1ccc(NS(=O)(=O)c2ccc3ncsc3c2)c(Br)c1
null
Cc1ccc(N)c(Br)c1
O=S(=O)(Cl)c1ccc2ncsc2c1
null
[Br:1][C:2]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:3]=1[NH2:4].[S:10]1[C:14]2[CH:15]=[C:16]([S:19](Cl)(=[O:21])=[O:20])[CH:17]=[CH:18][C:13]=2[N:12]=[CH:11]1>>[Br:1][C:2]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:3]=1[NH:4][S:19]([C:16]1[CH:17]=[CH:18][C:13]2[N:12]=[CH:11][S:10][C:14]=2[CH:15]=1)(=[O:20])=[O:21]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,263,189
[Ti+4]
CC(C)[O-]
null
null
ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0
2013-01-01T00:02:00
true
(General Grignard addition reaction procedure): a mixture of 2-Chloro-4-(5-formyl-pyridin-3-yl)-benzonitrile (0.243 g, 1 mmol), titanium(IV) isopropoxide (0.586 mL, 2.000 mmol), ethanesulfonamide (0.109 g, 1.000 mmol) in Toluene (20 mL) was heated to reflux for 4 hr. After concentration, the residue was dissolved in THF (15 mL) and cooled to −40° C. A solution of isopropenylmagnesium bromide (1.500 mL, 3.000 mmol) was added dropwise and the resulting mixture was slowly warmed up to −20° C. and stirred at this temperature for 4 hr. After quenched by NH4Cl solution, filtration, extraction with CH2Cl2, the solution was dried over Na2SO4, and concentrated, the residue was purified by flash column (MeOH—CH2Cl2, v/v, 1%-3%) and yielded a yellow solid (90 mg). Enantiomers were separated by 40% EtOH 60% heptane on a Chiralpak IA column. First peak 14 min (enantiomer 1), second peak 20 min (enantiomer 2). ESI-MS m/z: 378.1 [M+H]+, 1H NMR (400 MHz, CDCl3): δ 0.93 (d, J=6.7 Hz, 3H), 1.06 (d, J=6.7 Hz, 3H), 1.21 (t, J=8.0 Hz, 3H), 2.04-2.11 (m, 1H), 2.76-2.91 (m, 2H), 4.36 (t, J=7.4 Hz, 1H), 4.90 (d, J=7.6 Hz, 1H), 7.58 (d, J=8.2 Hz, 1H), 7.72 (s, 1H), 7.77 (s, 1H), 7.78 (d, J=8.2 Hz, 1H), 8.61 (s, 1H), 8.77 (s, 1H).
CCS(=O)(=O)NC(c1cncc(-c2ccc(C#N)c(Cl)c2)c1)C(C)C
null
C=C(C)[Mg]Br
N#Cc1ccc(-c2cncc(C=O)c2)cc1Cl
CCS(N)(=O)=O
[Cl:1][C:2]1[CH:9]=[C:8]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([CH:16]=O)[CH:15]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[CH2:18]([S:20]([NH2:23])(=[O:22])=[O:21])[CH3:19].[C:24]([Mg]Br)([CH3:26])=[CH2:25]>C1(C)C=CC=CC=1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[Cl:1][C:2]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14]([CH:16]([NH:23][S:20]([CH2:18][CH3:19])(=[O:22])=[O:21])[CH:24]([CH3:26])[CH3:25])[CH:13]=[N:12][CH:11]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]
4
Cc1ccccc1
null
null
-40
null
23.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,193,252
null
null
null
null
ord_dataset-4e81c470cc3b429faf5e1caa50f70a98
2012-01-01T00:08:00
true
Prepared according to the procedure described in Example 6, Step 5, using the following starting materials: [3-(4-bromo-2-bromomethyl-phenoxy)-4-methoxy-phenyl]-acetic acid methyl ester and (4R,5S)-5-(3,5-difluoro-phenyl)-4-methyl-oxazolidin-2-one.
COC(=O)Cc1ccc(OC)c(Oc2ccc(Br)cc2CN2C(=O)O[C@@H](c3cc(F)cc(F)c3)[C@H]2C)c1
null
COC(=O)Cc1ccc(OC)c(Oc2ccc(Br)cc2CBr)c1
C[C@H]1NC(=O)O[C@H]1c1cc(F)cc(F)c1
null
[CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([O:13][C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][C:15]=2[CH2:21]Br)[CH:6]=1.[F:24][C:25]1[CH:26]=[C:27]([C@@H:32]2[O:36][C:35](=[O:37])[NH:34][C@@H:33]2[CH3:38])[CH:28]=[C:29]([F:31])[CH:30]=1>>[CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([O:13][C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][C:15]=2[CH2:21][N:34]2[C@H:33]([CH3:38])[C@H:32]([C:27]3[CH:26]=[C:25]([F:24])[CH:30]=[C:29]([F:31])[CH:28]=3)[O:36][C:35]2=[O:37])[CH:6]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
434,876
null
null
null
null
ord_dataset-386da077ab2340638cada986e2ef0770
1999-01-01T00:07:00
true
TFA (4 mL) was added to a CH2Cl2 solution (10 mL) of 7-3 (120 mg, 0.48 mmol) and the solution stirred under ambient conditions for 2 h and concentrated to dryness. The residue was azeotroped with toluene (3×25 mL) to provide 7-4 as a light-yellow semi-solid.
C[C@H](Cc1ccccn1)NC(=O)O
null
C[C@H](Cc1ccccn1)NC(=O)OC(C)(C)C
null
null
[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].C([O:12][C:13](=[O:24])[NH:14][C@H:15]([CH3:23])[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1)(C)(C)C>C(Cl)Cl>[F:4][C:3]([F:6])([F:5])[C:1]([OH:7])=[O:2].[CH3:23][C@@H:15]([NH:14][C:13](=[O:12])[OH:24])[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1
2
ClCCl
O=C(O)C(F)(F)F
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
226,636
CCCCCCCCCCCCCCCC[N+](C)(C)C
[Cl-]
null
null
ord_dataset-67612e25ea9d4b29966a776893a43d59
1991-01-01T00:04:00
true
Employing 3-(octadecyloxy)propanol (5 g), 1,3-dibromopropane (9.2 g) and cetyltrimethylammonium chloride (0.97 g), a reaction and aftertreatment are conducted in the same manner as those in Reference Example 4 to obtain the above-titled compound (0.53 g).
CCCCCCCCCCCCCCCCCCOCCCOCCCBr
null
CCCCCCCCCCCCCCCCCCOCCCO
BrCCCBr
null
[CH2:1]([O:19][CH2:20][CH2:21][CH2:22][OH:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[Br:24][CH2:25][CH2:26][CH2:27]Br>[Cl-].C([N+](C)(C)C)CCCCCCCCCCCCCCC>[Br:24][CH2:25][CH2:26][CH2:27][O:23][CH2:22][CH2:21][CH2:20][O:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
null
null
null
null
null
7.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
491,211
[I-]
[Na+]
null
null
ord_dataset-37b0416f244344a08cf357e851eedf2a
2001-01-01T00:01:00
true
A mixture of 1-piperidin-4-yl-1,3-dihydro-benzimidazol-2-one (0.5 g, 2.3 mmol), 2-phenyl-ethylbromid (0.34 ml, 2.5 mmol), triethylamine (0.35 ml, 2.5 mmol) and sodium iodide (0.01 g, 0.67 mmol) in dry N,N-dimethyl foramide (5 ml) was stirred at 100° C. for 3 hours. The reaction mixture was cooled to room temperature, and then poured into water (20 ml). The product precipitated upon stirring on a ice/water bath and was isolated by filtration. Yield 0.45 g (1.4 mmol, 61%). M.p. 181-185° C.
O=c1[nH]c2ccccc2n1C1CCN(CCc2ccccc2)CC1
null
BrCCc1ccccc1
O=c1[nH]c2ccccc2n1C1CCNCC1
null
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[NH:9][C:8]2=[O:16])[CH2:3][CH2:2]1.[C:17]1([CH2:23][CH2:24]Br)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(CC)CC)C.[I-].[Na+]>CN(C)C=O.O>[CH2:24]([N:1]1[CH2:2][CH2:3][CH:4]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[NH:9][C:8]2=[O:16])[CH2:5][CH2:6]1)[CH2:23][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
3
O
CCN(CC)CC
CN(C)C=O
100
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
781,872
O=C([O-])[O-]
[K+]
null
null
ord_dataset-8034115bd2ec4d3e95bd3ff7cfde0bde
2007-01-01T00:07:00
true
5,10,15,20-tetrakis-(4-Hydroxy-phenyl)-porphyrin (170 mg, 0.25 mmol) is dissolved and K2CO3 (0.65 g, mmol) is suspended in DMF (30 mL). To the vigorously stirred reaction mixture a solution of 1-bromotetradecane (0.1 mL, 0.45 mmol) in DMF (10 mL) is added dropwise at 50° C. during 30 mins and the mixture is heated for 1.5 h. After evaporation of solvent, the residue is dissolved in toluene:ethanol (1:1 by vol., ca. 5 mL) and purified by chromatography using a column (5×25 cm) of silica gel (Merck 60) which is washed with toluene. After the elution of the first 3 fractions, elution is continued using toluene:ethyl acetate (2:1 by vol.). The fifth compound eluted is collected, the solvent evaporated and the residue dried under high vacuum to afford product as violet crystals.
CCCCCCCCCCCCCCOc1ccc(-c2c3nc(c(-c4ccc(O)cc4)c4ccc([nH]4)c(-c4ccc(O)cc4)c4nc(c(-c5ccc(O)cc5)c5ccc2[nH]5)C=C4)C=C3)cc1
null
Oc1ccc(-c2c3nc(c(-c4ccc(O)cc4)c4ccc([nH]4)c(-c4ccc(O)cc4)c4nc(c(-c5ccc(O)cc5)c5ccc2[nH]5)C=C4)C=C3)cc1
CCCCCCCCCCCCCCBr
null
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[NH:13][C:12]([C:14]([C:46]4[CH:51]=[CH:50][C:49]([OH:52])=[CH:48][CH:47]=4)=[C:15]4[N:45]=[C:18]([C:19]([C:38]5[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=5)=[C:20]5[NH:37][C:23](=[C:24]([C:30]6[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=6)[C:25]6[CH:26]=[CH:27][C:28]=2[N:29]=6)[CH:22]=[CH:21]5)[CH:17]=[CH:16]4)=[CH:11][CH:10]=3)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH3:73]>CN(C=O)C>[OH:52][C:49]1[CH:48]=[CH:47][C:46]([C:14]2[C:12]3[NH:13][C:9]([C:8]([C:5]4[CH:6]=[CH:7][C:2]([O:1][CH2:73][CH2:72][CH2:71][CH2:70][CH2:69][CH2:68][CH2:67][CH2:66][CH2:65][CH2:64][CH2:63][CH2:62][CH2:61][CH3:60])=[CH:3][CH:4]=4)=[C:28]4[N:29]=[C:25]([C:24]([C:30]5[CH:31]=[CH:32][C:33]([OH:36])=[CH:34][CH:35]=5)=[C:23]5[NH:37][C:20](=[C:19]([C:38]6[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=6)[C:18]6[CH:17]=[CH:16][C:15]=2[N:45]=6)[CH:21]=[CH:22]5)[CH:26]=[CH:27]4)=[CH:10][CH:11]=3)=[CH:51][CH:50]=1
null
CN(C)C=O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
164,056
Cl
null
null
null
ord_dataset-1385ebf1988241e49636101695ad79e4
1987-01-01T00:10:00
true
To 0.09 g of 6-(2-ethoxycarbonylethenyl)-1-(4-hydroxy-2-methylphenyl)-4-oxo-1,4-dihydronicotinic acid was added 3 ml of 6N hydrochloric acid, and they were reacted at 100° C. for 1.5 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure, and to the crystals thus formed were added 3 ml of diethyl ether, and the resulting mixture was filtered to obtain 0.08 g of 6-(2-carboxyethenyl)-1-(4-hydroxy-2-methylphenyl)-4-oxo-1,4-dihydronicotinic acid having a melting point of 280° C. or more.
Cc1cc(O)ccc1-n1cc(C(=O)O)c(=O)cc1C=CC(=O)O
null
CCOC(=O)C=Cc1cc(=O)c(C(=O)O)cn1-c1ccc(O)cc1C
null
null
C([O:3][C:4]([CH:6]=[CH:7][C:8]1[N:9]([C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][C:19]=2[CH3:25])[CH:10]=[C:11]([C:15](=[O:17])[CH:16]=1)[C:12]([OH:14])=[O:13])=[O:5])C.Cl>C(OCC)C>[C:4]([CH:6]=[CH:7][C:8]1[N:9]([C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][C:19]=2[CH3:25])[CH:10]=[C:11]([C:15](=[O:17])[CH:16]=1)[C:12]([OH:14])=[O:13])([OH:5])=[O:3]
null
CCOCC
null
null
null
null
96.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
705,365
[Cl-]
null
null
null
ord_dataset-c408dfed796e4354b61e312e67f7143f
2006-01-01T00:04:00
true
The preparation was carried out in accordance with general synthesis instructions 4 from 3-pyrrol-1-yl-propionitrile and (2-methoxy-benzylidene)-dimethyl-ammonium chloride, which had been prepared in accordance with example 7.
COc1ccccc1C(c1cccn1CCC#N)N(C)C
null
N#CCCn1cccc1
COc1ccccc1C=[N+](C)C
null
[N:1]1([CH2:6][CH2:7][C:8]#[N:9])[CH:5]=[CH:4][CH:3]=[CH:2]1.[Cl-].[CH3:11][O:12][C:13]1[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=1[CH:15]=[N+:16]([CH3:18])[CH3:17]>>[CH3:18][N:16]([CH:15]([C:14]1[CH:19]=[CH:20][CH:21]=[CH:22][C:13]=1[O:12][CH3:11])[C:2]1[N:1]([CH2:6][CH2:7][C:8]#[N:9])[CH:5]=[CH:4][CH:3]=1)[CH3:17]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,437,987
null
null
null
null
ord_dataset-275a3da8f45f4536ad29727f0ef9ba66
2014-01-01T00:06:00
true
HONH2 (50% aqueous, 4 mL) was added to II (120 mg, 0.3 mmol) in MeOH (4 mL) and DMF (2 mL) at rt. The reaction mixture was stirred for 24 h, after which the solvents were evaporated under reduced pressure. The resulting residue was dissolved and co-evaporated with toluene (3×5 mL) then was purified by silica gel column chromatography eluting with CH2Cl2/MeOH (100:2 to 100:8) to furnish III as a yellow oil (28 mg, 23%).
O=C(CCCCCCN(c1ccccn1)c1cc(-c2ccccc2)ccn1)NO
null
CCOC(=O)CCCCCCN(c1ccccn1)c1cc(-c2ccccc2)ccn1
NO
null
[OH:1][NH2:2].C([O:5][C:6](=O)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]([C:20]1[CH:25]=[C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:23]=[CH:22][N:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)C>CO.CN(C=O)C>[OH:1][NH:2][C:6](=[O:5])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]([C:20]1[CH:25]=[C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:23]=[CH:22][N:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1
24
CO
CN(C)C=O
null
null
23
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
919,111
Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
[Cu]I
null
null
ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d
2009-01-01T00:11:00
true
{4-[5-Bromothiophen-2-yl]-pyrimidin-2-yl}-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine (100 mg, 0.253 mmol), PdCl2(PPh3)2 (18 mg, 0.025 mmol), 1,1-dimethyl-prop-2-ynylamine (0.03 ml, 0.253 mmol) and CuI (15 mg) were dissolved in triethylamine (25 ml) and refluxed for 1 hour. The reaction mixture was filtered, evaporated to dryness and taken up in DCM, filtered and evaporated again and the residue crystallized from ether to give the title compound as red-yellow crystals. Yield: 50 mg (50%).
CC(C)(N)C#Cc1ccc(-c2ccnc(NC3CC(C)(C)NC(C)(C)C3)n2)s1
null
CC1(C)CC(Nc2nccc(-c3ccc(Br)s3)n2)CC(C)(C)N1
C#CC(C)(C)N
null
Br[C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH:14]3[CH2:19][C:18]([CH3:21])([CH3:20])[NH:17][C:16]([CH3:23])([CH3:22])[CH2:15]3)[N:8]=2)=[CH:4][CH:3]=1.[CH3:24][C:25]([NH2:29])([CH3:28])[C:26]#[CH:27]>C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[NH2:29][C:25]([CH3:28])([CH3:24])[C:26]#[C:27][C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH:14]3[CH2:19][C:18]([CH3:21])([CH3:20])[NH:17][C:16]([CH3:23])([CH3:22])[CH2:15]3)[N:8]=2)=[CH:4][CH:3]=1
null
CCN(CC)CC
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,275,505
null
null
null
null
ord_dataset-d5c54236ecd94d61aaa071461bcfc426
2013-01-01T00:04:00
true
In a reaction vial was placed a stir bar, 1-[2-(2-dimethylamino-ethoxy)-4-methanesulfonyl-phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-ol (50 mg), POCl3 (0.5 mL) and N,N-dimethylaniline (15 μl). The reaction mixture was stirred at 100° C. for 1 hour. Upon cooling the reaction mixture to the room temperature, a white precipitate formed. The mixture was left sealed over the weekend at room temperature. After concentrated under the vacuum, the residue was washed with Et2O and filtered to give {2-[2-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-5-methanesulfonyl-phenoxy]-ethyl}-dimethyl-amine as a white solid. Exact mass calculated for C16H18ClN5O3S 395.08, found 396 (MH+).
CN(C)CCOc1cc(S(C)(=O)=O)ccc1-n1ncc2c(Cl)ncnc21
null
CN(C)CCOc1cc(S(C)(=O)=O)ccc1-n1ncc2c(O)ncnc21
O=P(Cl)(Cl)Cl
null
[CH3:1][N:2]([CH3:26])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[C:10]([S:12]([CH3:15])(=[O:14])=[O:13])[CH:9]=[CH:8][C:7]=1[N:16]1[C:20]2=[N:21][CH:22]=[N:23][C:24](O)=[C:19]2[CH:18]=[N:17]1.O=P(Cl)(Cl)[Cl:29].CN(C)C1C=CC=CC=1>>[Cl:29][C:24]1[N:23]=[CH:22][N:21]=[C:20]2[N:16]([C:7]3[CH:8]=[CH:9][C:10]([S:12]([CH3:15])(=[O:14])=[O:13])=[CH:11][C:6]=3[O:5][CH2:4][CH2:3][N:2]([CH3:26])[CH3:1])[N:17]=[CH:18][C:19]=12
1
CN(C)c1ccccc1
null
null
100
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,595,732
CCn1nnc2c(N3CCC(F)(F)C3)nc(C(C)(C)C)nc21
Cl
null
null
ord_dataset-e8c6a25568b64529b960953990e6921f
2015-01-01T00:06:00
true
In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3-ethyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 61), the title compound was prepared from 5-tert-Butyl-7-(3,3,4,4-tetrafluoro-pyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 5-(chloromethyl)-1-methyl-1H-1,2,3-triazole hydrochloride and isolated as light-yellow gum. MS(m/e): 414.3 (MH+).
Cn1nncc1Cn1nnc2c(N3CC(F)(F)C(F)(F)C3)nc(C(C)(C)C)nc21
null
Cn1nncc1CCl
CC(C)(C)c1nc(N2CC(F)(F)C(F)(F)C2)c2nn[nH]c2n1
null
C(C1N=C(N2CCC(F)(F)C2)C2N=NN(CC)C=2N=1)(C)(C)C.[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][C:39]([F:42])([F:41])[C:38]([F:44])([F:43])[CH2:37]2)[C:30]2[N:35]=[N:34][NH:33][C:31]=2[N:32]=1)([CH3:26])([CH3:25])[CH3:24].Cl.Cl[CH2:47][C:48]1[N:52]([CH3:53])[N:51]=[N:50][CH:49]=1>>[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][C:39]([F:41])([F:42])[C:38]([F:43])([F:44])[CH2:37]2)[C:30]2[N:35]=[N:34][N:33]([CH2:47][C:48]3[N:52]([CH3:53])[N:51]=[N:50][CH:49]=3)[C:31]=2[N:32]=1)([CH3:26])([CH3:24])[CH3:25]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,700,802
CCc1ccc2cc(N)c(C(=O)Nc3cnc4c(c3N3CCC[C@H](N)C3)CC[C@@H]4O)nc2c1
null
null
null
ord_dataset-54347fcace774f89850681d6dec8009f
2016-01-01T00:03:00
true
The diastereoisomers are assigned as 3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]-(7R)-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-7-ethylquinoline-2-carboxamide and 3-amino-N-{4-[(3S)-3-aminopiperidin-1-yl]-(7S)-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-7-ethylquinoline-2-carboxamide.
CCc1ccc2cc(N)c(C(=O)Nc3cnc4c(c3N3CCC[C@H](N)C3)CCC4O)nc2c1
null
CCc1ccc2cc(N)c(C(=O)Nc3cnc4c(c3N3CCC[C@H](N)C3)CC[C@H]4O)nc2c1
null
null
[NH2:1][C:2]1[C:3]([C:14]([NH:16][C:17]2[C:18]([N:27]3[CH2:32][CH2:31][CH2:30][C@H:29]([NH2:33])[CH2:28]3)=[C:19]3[CH2:25][CH2:24][C@@H:23]([OH:26])[C:20]3=[N:21][CH:22]=2)=[O:15])=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([CH2:12][CH3:13])[CH:6]=2.NC1C(C(NC2C(N3CCC[C@H](N)C3)=C3CC[C@H](O)C3=NC=2)=O)=NC2C(C=1)=CC=C(CC)C=2>>[NH2:1][C:2]1[C:3]([C:14]([NH:16][C:17]2[C:18]([N:27]3[CH2:32][CH2:31][CH2:30][C@H:29]([NH2:33])[CH2:28]3)=[C:19]3[CH2:25][CH2:24][CH:23]([OH:26])[C:20]3=[N:21][CH:22]=2)=[O:15])=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([CH2:12][CH3:13])[CH:6]=2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
233,363
[Na+]
[Na]
null
null
ord_dataset-ed79ebfb2fff4cdbbc3a609c8edeac11
1991-01-01T00:08:00
true
To a solution of sodium methoxide prepare from sodium (0.2 g) and absolute methanol (9 ml) was added 7-(3-aminomethyl-1-pyrrolidinyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (0.5 g) and the mixture in sealed tube was stirred for 86 hours at 140° to 150° C. and then concentrated. Small amount of water was added to the residue, and the solution was adjusted pH 7 with acetic acid and then concentrated. The resulting residue was purified by silica gel column chromatography eluting with chloroform-methanol-concentrated aqueous ammonia (20:6:1) and recrystallized from methanol to give the title compound (40 mg) as pale yellow prisms, mp 225°-228.5° C. (decompd.).
COc1c(N2CCC(CN)C2)c(F)cc2c(=O)c(C(=O)O)cn(C3CC3)c12
null
C[O-]
NCC1CCN(c2c(F)cc3c(=O)c(C(=O)O)cn(C4CC4)c3c2F)C1
null
[CH3:1][O-:2].[Na+].[Na].[NH2:5][CH2:6][CH:7]1[CH2:11][CH2:10][N:9]([C:12]2[C:21](F)=[C:20]3[C:15]([C:16](=[O:29])[C:17]([C:26]([OH:28])=[O:27])=[CH:18][N:19]3[CH:23]3[CH2:25][CH2:24]3)=[CH:14][C:13]=2[F:30])[CH2:8]1>CO>[NH2:5][CH2:6][CH:7]1[CH2:11][CH2:10][N:9]([C:12]2[C:21]([O:2][CH3:1])=[C:20]3[C:15]([C:16](=[O:29])[C:17]([C:26]([OH:28])=[O:27])=[CH:18][N:19]3[CH:23]3[CH2:25][CH2:24]3)=[CH:14][C:13]=2[F:30])[CH2:8]1
86
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,035,843
null
null
null
null
ord_dataset-3af92aec23dc4810b92eb0d8c60023ee
2011-01-01T00:03:00
true
2-Chloro-4-fluoro-5-nitro-phenylamine (1.4 g, 7.4 mmol) was added to a solution of 5-(chloromethyl)-N2-methoxy-N2,N4-dimethylpyridine-2,4-diamine from example A16 (1.6 g, 7.4 mmol) in pyridine (30 mL) and the mixture was stirred at 50° C. for 8 hours. The reaction mixture was concentrated under reduced pressure and the solid residue was thoroughly washed with water to give 5-((2-chloro-4-fluoro-5-nitrophenylamino)methyl)-N2-methoxy-N2,N4-dimethylpyridine-2,4-diamine (1.5 g, 56% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.01 (s, 1H), 7.76 (d, J=8.4 Hz, 1 H), 7.71 (s, 1 H), 7.34 (d, J=8 Hz, 1 H), 6.56 (m, 1 H), 5.98 (s, 1 H), 4.36 (d, J=4 Hz, 2 H), 3.71 (s, 3 H), 3.31 (s, 3 H), 2.91-2.92 (d, J=4 Hz, 3 H); MS (ESI) m/z: 369.9 [M+H]+.
CNc1cc(N(C)OC)ncc1CNc1cc([N+](=O)[O-])c(F)cc1Cl
null
CNc1cc(N(C)OC)ncc1CCl
Nc1cc([N+](=O)[O-])c(F)cc1Cl
null
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][C:3]=1[NH2:12].Cl[CH2:14][C:15]1[C:16]([NH:25][CH3:26])=[CH:17][C:18]([N:21]([O:23][CH3:24])[CH3:22])=[N:19][CH:20]=1>N1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][C:3]=1[NH:12][CH2:14][C:15]1[C:16]([NH:25][CH3:26])=[CH:17][C:18]([N:21]([O:23][CH3:24])[CH3:22])=[N:19][CH:20]=1
8
c1ccncc1
null
null
50
56
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
66,491
CCOC(=O)Cl
N
null
null
ord_dataset-8af141577c90485cb9c91079a5ef96b3
1980-01-01T00:05:00
true
An amount of 55 mg of 2-(10,11-dihydro dibenzo[b,f]thiepin-2-yl)-propionic acid was dissolved in 0.5 ml of chloroform solution containing 0.02 ml of triethylamine and the resulting mixture was added dropwise with ice-cooling over a period of 5 minutes to 0.5 ml of chloroform solution containing 0.02 ml of ethyl chlorocarbonate. The mixture was stirred for 10 minutes at the same temperature, then at room temperature for 30 minutes after introduction of ammonia gas. After the completion of the reaction, to this was added water and the resulting mixture was extracted with chloroform. The extract was washed with dilute sodium hydroxide solution, then saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The solvent was distilled off to obtain pale brown crystals, which were chromatographed over silica gel, eluted with chloroform, and there were obtained pale yellow crystals. These were recrystallized from benzene-n-hexane to give 26 mg of 2-(10,11-dihydro dibenzo[b,f]thiepin-2-yl)-propionamide as colorless crystals having a melting point of 135°-135.5° C.
CC(C(N)=O)c1ccc2c(c1)CCc1ccccc1S2
null
CC(C(=O)O)c1ccc2c(c1)CCc1ccccc1S2
CCN(CC)CC
null
[CH:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[S:6][C:5]=2[CH:4]=[CH:3][C:2]=1[CH:16]([CH3:20])[C:17](O)=[O:18].C([N:23](CC)CC)C.C(Cl)(=O)OCC.N>C(Cl)(Cl)Cl.O>[CH:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[S:6][C:5]=2[CH:4]=[CH:3][C:2]=1[CH:16]([CH3:20])[C:17]([NH2:23])=[O:18]
0.17
ClC(Cl)Cl
O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,633,823
null
null
null
null
ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d
2015-01-01T00:09:00
true
To the solution of 1-(6-chloro-9-methyl-9H-purin-2-yl)butan-1-ol (1.8 g, 7.47 mmol) in dioxane (10 ml) was added 30% w/w water solution of ammonia (20 ml). The reaction mixture was stirred overnight in an autoclave at 70° C. The solution was evaporated at atmospheric pressure at 50° C. and then under reduced pressure. The residue was purified by flash chromatography (DCM/MeOH: 95/5).
CCCC(O)c1nc(N)c2ncn(C)c2n1
null
CCCC(O)c1nc(Cl)c2ncn(C)c2n1
N
null
Cl[C:2]1[N:10]=[C:9]([CH:11]([OH:15])[CH2:12][CH2:13][CH3:14])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH3:16].O.[NH3:18]>O1CCOCC1>[NH2:18][C:2]1[N:10]=[C:9]([CH:11]([OH:15])[CH2:12][CH2:13][CH3:14])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH3:16]
8
O
C1COCCO1
null
70
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
220,022
Cl
NO
null
null
ord_dataset-6cb04513a4a244c0b612b566096f4b3d
1990-01-01T00:12:00
true
A solution of 0.1 mol of p-aminobenzaldehyde ethylene glycol acetal in 100 mL of anhydrous THF is added dropwise over 10 minutes to a solution of 0.1 mol of methyl 2-isocyanato-4-methyl-4-pentenoate and 0.35 mol pyridine in 100 mL THF at room temperature under N2. The reaction mixture is stirred at room temperature for 2 hours. After 2 hours the solvent is removed by rotary evaporator. A solution of 0.11 mmol hydroxylamine hydrochloride and 0.1 mol trimethyl orthoformate in CH3OH is added, and the reaction mixture is heated to reflux under N2 for 1 hour. The reaction mixture is reduced to about 1/4 volume by rotary evaporator, and water is added. The product, N-[4-(hydroxyiminomethyl)phenyl]-N'-[1-(1-methoxycarbonyl-3-methyl-3-butenyl]urea, is isolated by filtration and dried in vacuo.
C=C(C)CC(NC(N)=O)C(=O)OC
null
C=C(C)CC(N=C=O)C(=O)OC
c1ccncc1
null
[N:1]([CH:4]([CH2:9][C:10]([CH3:12])=[CH2:11])[C:5]([O:7][CH3:8])=[O:6])=[C:2]=[O:3].[N:13]1C=CC=CC=1.Cl.NO.C(OC)(OC)OC>C1COCC1.CO>[CH3:8][O:7][C:5]([CH:4]([NH:1][C:2]([NH2:13])=[O:3])[CH2:9][C:10]([CH3:12])=[CH2:11])=[O:6]
2
CO
COC(OC)OC
C1CCOC1
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,282,001
CCCC[N+](CCCC)(CCCC)CCCC
[F-]
null
null
ord_dataset-d5c54236ecd94d61aaa071461bcfc426
2013-01-01T00:04:00
true
To 1-Triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid methyl ester (531, 0.950 g, 2.9 mmol) in tetrahydrofuran (20.0 mL) was added tetrabutyl-ammonium fluoride, trihydrate (1.20 g, 3.8 mmol). The reaction was stirred at room temperature for 10 minutes. The reaction was concentrated and purified with silica gel column chromatography eluting with 4% methanol in methylene chloride to give the compound as a white solid (532, 300 mg, 60%). MS(ESI) [M+H+]+=177.2.
COC(=O)c1cnc2[nH]ccc2c1
null
COC(=O)c1cnc2c(ccn2[Si](C(C)C)(C(C)C)C(C)C)c1
null
null
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[CH:12][N:11]([Si](C(C)C)(C(C)C)C(C)C)[C:8]2=[N:9][CH:10]=1)=[O:4].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[CH:12][NH:11][C:8]2=[N:9][CH:10]=1)=[O:4]
0.17
C1CCOC1
null
null
25
null
58.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
210,197
CS(=O)(=O)O
null
null
null
ord_dataset-e0a818f9350b46cdb184d2ac404ede9f
1990-01-01T00:06:00
true
2.4 g (0.008 mol) of 2-methoxycarbonyl-4-phenylthiophen-3-ylsulfonamide, 2.2 g of N-(4,6-dimethoxypyrimidin-2-yl)phenylcarbamate, 1.2 g of 1,8-diazabicyclo[5.4.0]undec-7-ene and 30 ml of acetonitrile are stirred for 16 hours at room temperature. The reaction mixture is then poured into a mixture of ice and water and acidified with methanesulfonic acid. The resultant precipitate is filtered, washed with water and dried, affording 3.4 g (95%) of N-(2-methoxycarbonyl-4-phenylthiophen-3-ylsulfonyl)-N'-(4,6-dimethoxypyrimidin-2-yl)urea with a melting point of 225°-227° C.
COC(=O)c1scc(-c2ccccc2)c1S(=O)(=O)NC(=O)Nc1nc(OC)cc(OC)n1
null
COC(=O)c1scc(-c2ccccc2)c1S(N)(=O)=O
COc1cc(OC)nc(N(C(=O)[O-])c2ccccc2)n1
null
[CH3:1][O:2][C:3]([C:5]1[S:6][CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:9]=1[S:10]([NH2:13])(=[O:12])=[O:11])=[O:4].[CH3:20][O:21][C:22]1[CH:27]=[C:26]([O:28][CH3:29])[N:25]=[C:24]([N:30](C2C=CC=CC=2)[C:31](=O)[O-:32])[N:23]=1.N12CCCN=C1CCCCC2.CS(O)(=O)=O>O.C(#N)C>[CH3:1][O:2][C:3]([C:5]1[S:6][CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:9]=1[S:10]([NH:13][C:31]([NH:30][C:24]1[N:23]=[C:22]([O:21][CH3:20])[CH:27]=[C:26]([O:28][CH3:29])[N:25]=1)=[O:32])(=[O:12])=[O:11])=[O:4]
null
CC#N
O
C1CCC2=NCCCN2CC1
null
88.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
929,887
null
null
null
null
ord_dataset-d8a5dc784dde4465894ec7c69d2e3ba6
2010-01-01T00:01:00
true
The title compound was prepared from 2-(2-chloro-pyridin-4-yl)-4-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-pyrimidine (example E.6) (0.202 g, 0.5 mmol) and commercially available 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.14 g, 0.65 mmol) according to the general procedure VI. Obtained as a light yellow solid (0.18 g, 80%). MS (ISP) 462.0 [(M+H)+]; mp 226° C.
Nc1ccc(-c2cc(-c3nc(-c4ccc(C(F)(F)F)cc4)cc(C(F)(F)F)n3)ccn2)cn1
null
FC(F)(F)c1ccc(-c2cc(C(F)(F)F)nc(-c3ccnc(Cl)c3)n2)cc1
CC1(C)OB(c2ccc(N)nc2)OC1(C)C
null
Cl[C:2]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=3)[N:9]=2)[CH:5]=[CH:4][N:3]=1.[NH2:28][C:29]1[CH:34]=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][N:30]=1>>[F:15][C:14]([F:17])([F:16])[C:12]1[CH:11]=[C:10]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=2)[N:9]=[C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:32]3[CH:31]=[N:30][C:29]([NH2:28])=[CH:34][CH:33]=3)[CH:7]=2)[N:13]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,354,068
null
null
null
null
ord_dataset-6034127657614f02860ed057b62b882e
2013-01-01T00:10:00
true
The title compound was prepared from (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one and 4-bromo-2,6-dimethylpyridine-N-oxide following a procedure analogous to that described in Example 1 Step 2. LC-MS Method 2 tR=1.185, m/z=459.1; 1H NMR (CDCl3) 1.11 (s, 3H), 1.18 (s, 3H), 1.57 (d, 3H), 2.20 (s, 2H), 2.22-2.35 (m, 2H), 2.38-2.49 (m, 1H), 2.72 (s, 6H), 2.91 (m, 1H), 5.70 (m, 1H), 7.08 (d, 2H), 7.31 (m, 3H), 7.37 (m, 4H), 7.43 (s, 2H).
Cc1cc(-c2ccc([C@H](C)N3CC[C@](CC(C)(C)O)(c4ccccc4)OC3=O)cc2)cc(C)[n+]1[O-]
null
Cc1cc(Br)cc(C)[n+]1[O-]
C[C@@H](c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
null
[OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.Br[C:37]1[CH:42]=[C:41]([CH3:43])[N+:40]([O-:44])=[C:39]([CH3:45])[CH:38]=1>>[OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:37]3[CH:42]=[C:41]([CH3:43])[N+:40]([O-:44])=[C:39]([CH3:45])[CH:38]=3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,339,118
null
null
null
null
ord_dataset-08852243bba44cb28769a5833f1515fe
2013-01-01T00:09:00
true
The title compound was prepared in analogy to the procedure described in Step 14.1 but using 3-aminopyridine, 8-(2,6-dichloro-3,5-dimethoxy-phenyl)-2-(4-ethyl-piperazin-1-ylmethyl)-quinoxaline-5-carboxylic acid (Step 83.1) and stirring the reaction mixture for 2 days at rt. Title compound: ESI-MS: 581.0/583.2 [M+H]+; tR=3.04 min (System 1); TLC: Rf=0.33 (DCM/MeOH, 9:1).
CCN1CCN(Cc2cnc3c(C(=O)Nc4cccnc4)ccc(-c4c(Cl)c(OC)cc(OC)c4Cl)c3n2)CC1
null
Nc1cccnc1
CCN1CCN(Cc2cnc3c(C(=O)O)ccc(-c4c(Cl)c(OC)cc(OC)c4Cl)c3n2)CC1
null
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[Cl:8][C:9]1[C:14]([O:15][CH3:16])=[CH:13][C:12]([O:17][CH3:18])=[C:11]([Cl:19])[C:10]=1[C:20]1[C:29]2[N:28]=[C:27]([CH2:30][N:31]3[CH2:36][CH2:35][N:34]([CH2:37][CH3:38])[CH2:33][CH2:32]3)[CH:26]=[N:25][C:24]=2[C:23]([C:39](O)=[O:40])=[CH:22][CH:21]=1>C(Cl)Cl.CO>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:39]([C:23]2[C:24]3[N:25]=[CH:26][C:27]([CH2:30][N:31]4[CH2:36][CH2:35][N:34]([CH2:37][CH3:38])[CH2:33][CH2:32]4)=[N:28][C:29]=3[C:20]([C:10]3[C:9]([Cl:8])=[C:14]([O:15][CH3:16])[CH:13]=[C:12]([O:17][CH3:18])[C:11]=3[Cl:19])=[CH:21][CH:22]=2)=[O:40])[CH:3]=1
48
CO
ClCCl
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
842,654
null
null
null
null
ord_dataset-e2b35e721c2741999b0005d12691f9fe
2008-01-01T00:10:00
true
Following the procedure described above in Example 1, 4-[(3-bromo-4-methylphenyl)amino]-6-fluoro-[1,7]naphthyridine-3-carbonitrile (300 mg, 1.1 mmol, 1 eq) was reacted with 2-morpholin-4-yl-1-ethylamine (3 mL, 20 eq). The crude product was purified via preparative HPLC to obtain 67 mg product (18% yield):
Cc1ccc(Nc2c(C#N)cnc3cnc(NCCN4CCOCC4)cc23)cc1Br
null
NCCN1CCOCC1
Cc1ccc(Nc2c(C#N)cnc3cnc(F)cc23)cc1Br
null
[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][N:16]=[C:17](F)[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:21]#[N:22])[CH:5]=[CH:6][C:7]=1[CH3:8].[N:23]1([CH2:29][CH2:30][NH2:31])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1>>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][N:16]=[C:17]([NH:31][CH2:30][CH2:29][N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:21]#[N:22])[CH:5]=[CH:6][C:7]=1[CH3:8]
null
null
null
null
null
18
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
953,203
[BH4-]
[Na+]
null
null
ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8
2010-01-01T00:04:00
true
The title compound was prepared from D11 using a method similar to that described for D3 in Description 3A although the reaction was heated at 50° C. overnight prior to addition of sodium borohydride and no column chromatography was required. δH (CDCl3, 400 MHz) 7.11 (2H, d), 6.57 (2H, d), 3.69 (1H, br.s), 3.40 (6H, m), 2.83 (3H, s), 2.36 (4H, m), 1.45 (9H, s) [6 values corrected for incorrectly referenced TMS at 0.58 ppm on spectrum]. MS (ES+): 206.2, no molecular ion (MH+) observed.
CNc1ccc(CN2CCN(C(=O)OC(C)(C)C)CC2)cc1
null
CNc1ccc(CN2CCN(C(=O)OC(C)(C)C)[C@@H](C)C2)cc1
null
null
C[C@H:2]1[CH2:7][N:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][CH3:16])=[CH:11][CH:10]=2)[CH2:5][CH2:4][N:3]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].[BH4-].[Na+]>>[CH3:16][NH:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][N:6]2[CH2:7][CH2:2][N:3]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:4][CH2:5]2)=[CH:10][CH:11]=1
null
null
null
null
50
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
605,007
[Pd]
null
null
null
ord_dataset-273fda773e864aaf9b71a30a2d9f2162
2003-01-01T00:08:00
true
tert-Butyl 3-(benzyloxy)phenyl(methylsulfonyl)carbamate (2.6 g, 6.88 mmol) was dissolved in ethanol (25 mL), 10% palladium on carbon (0.75 g) and cyclohexene (1.5 mL) were added. The solution was heated to reflux for 3 hours. The solution was cooled and filtered through Celite. The solvent was removed in vacuo to yield crude title compound (1.93 g, 6.7 mmol).
CC(C)(C)OC(=O)N(c1cccc(OC[C@@H]2CO2)c1)S(C)(=O)=O
null
CCO
CC(C)(C)OC(=O)N(c1cccc(OCc2ccccc2)c1)S(C)(=O)=O
null
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([N:15]([S:23]([CH3:26])(=[O:25])=[O:24])[C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=[CH:13][CH:14]=1)[C:2]1C=CC=C[CH:3]=1.C1CCCCC=1.C([OH:35])C>[Pd]>[CH3:26][S:23]([N:15]([C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([O:8][CH2:1][C@@H:2]2[CH2:3][O:35]2)[CH:10]=1)[C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:19])[CH3:20])(=[O:25])=[O:24]
null
C1=CCCCC1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
162,455
CCOC(C)O
null
null
null
ord_dataset-f5dc3e448c204058b116bf1970695bef
1987-01-01T00:09:00
true
To a mixture of 2.66 g of 6-acetamido-8-bromo-1,7-naphthyridine and 6.51 g of 1-piperazine ethanol, 180 ml of ethoxyethanol was added. The resultant mixture was refluxed with stirring for 45 minutes. After the reaction, ethoxyethanol was distilled off under reduced pressure and chloroform was added to the residue. After thoroughly washing the chloroform solution with water, it was dried with anhydrous magnesium sulfate. Chloroform was distilled off under reduced pressure and the residue was purified by silica gel column chromatography, followed by recrystallization from a mixed solvent of ethanol and ether to obtain 2.6 g of 6-acetamido-8-[4-(2-hydroxyethyl)-1-piperazinyl]-1,7-naphthyridine (Compound No. 22) as light yellowish crystals (yield: 82.5%).
CC(=O)Nc1cc2cccnc2c(N2CCN(CCO)CC2)n1
null
CC(=O)Nc1cc2cccnc2c(Br)n1
OCCN1CCNCC1
null
[C:1]([NH:4][C:5]1[CH:6]=[C:7]2[C:12](=[C:13](Br)[N:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)(=[O:3])[CH3:2].[N:16]1([CH2:22][CH2:23][OH:24])[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1>C(OC(O)C)C>[C:1]([NH:4][C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([N:19]3[CH2:20][CH2:21][N:16]([CH2:22][CH2:23][OH:24])[CH2:17][CH2:18]3)[N:14]=1)[N:11]=[CH:10][CH:9]=[CH:8]2)(=[O:3])[CH3:2]
0.75
null
null
null
null
82.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
147,381
Cl
null
null
null
ord_dataset-2069a3db775a4d9f9310aca092ecbad8
1986-01-01T00:08:00
true
This example serves to illustrate procedure B of Scheme 2. To an ice-cooled solution of 1-(2-pyrimidinyl)piperazine (16.4 g, 0.1 mole) in 1N HCl (100 mL) was added dropwise bromine (15.98 g, 0.1 mole). After stirring at 0° for 0.5 hr, the mixture was heated to 100° until dissipation of the red color had occurred. The mixture is filtered, cooled, made alkaline with 50% NaOH and extracted with ether. The dried extract (MgSO4) was concentrated in vacuo to provide 14.5 g (62%) of product, m.p. 73°-75°.
Brc1cnc(N2CCNCC2)nc1
null
BrBr
c1cnc(N2CCNCC2)nc1
null
[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.[Br:13]Br>Cl>[Br:13][C:5]1[CH:6]=[N:1][C:2]([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[N:3][CH:4]=1
0.5
null
null
null
0
null
59.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
862,094
null
null
null
null
ord_dataset-b8b98725045d45bdbd73512048f4b47e
2009-01-01T00:02:00
true
To an ice-cooled suspension of 3-amino-1H-thieno[3,2-c]pyrazole-5-carboxylic acid methyl ester (35.5 mmol, 7.0 g) and N,N′-diisopropylethylamine (0.21 mol, 36.5 mL) in 71 mL of tetrahydrofuran were added, dropwise, 3.5 mL of ethyl chloroformate (36.6 mmol). After 1.5 hours, the cold suspension was concentrated under vacuum and diluted with dichloromethane. The organic phase was washed with buffer pH 4, sodium hydroxide 1 N, brine and dried over Na2SO4. The filtrate was evaporated to dryness and triturated with dichloromethane to give 6 g 1-ethyl 5-methyl 3-amino-1H-thieno[3,2-c]pyrazole-1,5-dicarboxylate (7)
CCOC(=O)n1nc(N)c2sc(C(=O)OC)cc21
null
COC(=O)c1cc2[nH]nc(N)c2s1
CCOC(=O)Cl
null
[CH3:1][O:2][C:3]([C:5]1[S:12][C:11]2[C:10]([NH2:13])=[N:9][NH:8][C:7]=2[CH:6]=1)=[O:4].CCN(C(C)C)C(C)C.Cl[C:24]([O:26][CH2:27][CH3:28])=[O:25]>O1CCCC1>[NH2:13][C:10]1[C:11]2[S:12][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][C:7]=2[N:8]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[N:9]=1
1.5
CCN(C(C)C)C(C)C
C1CCOC1
null
0
null
62.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
128,415
null
null
null
null
ord_dataset-d6b60b593b1c4668bc6843cd65a5d232
1985-01-01T00:04:00
true
30.4 g of 1-pentyl-4-(trans-4-pentylcyclohexyl)-cyclohexene [obtainable by reacting 4-(trans-4-pentylcyclohexyl)-cyclohexanone with pentyl-MgBr, hydrolysing the product to give 1-pentyl-4-(trans-4-pentylcyclohexyl)-cyclohexanol and dehydrating the latter], 2.7 g of liquid HCN, 0.1 g of palladium bis-[2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis-(diphenylphosphino)-butane] and 100 ml of acetonitrile are heated at 130° for 1 hour in an autoclave. The mixture is cooled, evaporated and worked up in the customary manner to give r-1-cyano-1-pentyl-cis-4-(trans-4-pentylcyclohexyl)-cyclohexane, m.p. 28°, c.p. 63°.
CCCCCC1(O)CCC([C@H]2CC[C@H](CCCCC)CC2)CC1
null
CCCCC[C@H]1CC[C@H](C2CCC(=O)CC2)CC1
CCCCCC1=CCC([C@H]2CC[C@H](CCCCC)CC2)CC1
null
[CH2:1]([C:6]1[CH2:11][CH2:10][CH:9]([C@H:12]2[CH2:17][CH2:16][C@H:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH2:14][CH2:13]2)[CH2:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5].C([C@H]1CC[C@H](C2CCC(=[O:40])CC2)CC1)CCCC>>[CH2:1]([C:6]1([OH:40])[CH2:11][CH2:10][CH:9]([C@H:12]2[CH2:17][CH2:16][C@H:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH2:14][CH2:13]2)[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
859,889
Cl
null
null
null
ord_dataset-93908aaae836460ebd48d733eccad483
2009-01-01T00:01:00
true
A solution of (3R) 3-amino-2-oxo-5-phenyl-1-(2,2,2-trifluorethyl)-2,3-dihydro-1H-1,4-benzodiazepine (Y.-J. Shi et al., Tetrahedron, 1999, 55, 909-918) (0.150 g, 0.45 mmol) and 4-nitrophenylchloroformate (0.091 g, 0.45 mmol) in dry tetrahydrofuran (2.5 mL) was cooled to 0° C. under argon. Triethylamine (0.063 mL, 0.45 mmol) was added and the reaction stirred for 1 h. A solution of 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride (0.130 g, 0.45 mmol) and triethylamine (0.190 mL) in dimethylsulfoxide (2.5 mL) was added. The reaction was allowed to come to room temperature and stirred overnight. The crude product was purified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution). The pure fractions were extracted with methylene chloride and saturated sodium bicarbonate. The organic layer was dried, filtered and evaporated. The product was taken up in methanol and treated with hydrogen chloride. The solvent was evaporated and the resulting solid was dried in vacuo, to yield the title compound (184 mg, 66% yield). MS 578.2118 (M+1) 1H NMR (500 MHz, C3OD) δ 8.02 (d, J=8 Hz, 1H), 8.00 (d, J=6 Hz, 1H), 7.80 (d, J=3 Hz, 2H), 7.60 (m, 3H), 7.50 (t, J=8 Hz, 2H), 7.45 (m, 1H), 7.39 (d, J=7 Hz, 1H), 7.34 (dd, J=6, 8 Hz, 1H), 5.55 (s, 1H), 5.26 (m, 1H), 4.61 (m, 2H), 4.35 (d, J=13 Hz, 2H), 3.08 (q, J=13 Hz, 2H), 2.40 (m, 2H), 1.91 (m, 2H).
O=C(N[C@@H]1N=C(c2ccccc2)c2ccccc2N(CC(F)(F)F)C1=O)N1CCC(n2c(=O)[nH]c3ncccc32)CC1
null
O=c1[nH]c2ncccc2n1C1CCNCC1
NC1N=C(c2ccccc2)c2ccccc2N(CC(F)(F)F)C1=O
null
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]([CH2:19][C:20]([F:23])([F:22])[F:21])[C:3]1=[O:24].C1C([N+]([O-])=O)=CC=C([Cl-][C:35]([O-])=[O:36])C=1.C(N(CC)CC)C.Cl.Cl.[O:47]=[C:48]1[NH:56][C:51]2=[N:52][CH:53]=[CH:54][CH:55]=[C:50]2[N:49]1[CH:57]1[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]1>O1CCCC1.CS(C)=O>[O:24]=[C:3]1[C@H:2]([NH:1][C:35]([N:60]2[CH2:61][CH2:62][CH:57]([N:49]3[C:50]4[C:51](=[N:52][CH:53]=[CH:54][CH:55]=4)[NH:56][C:48]3=[O:47])[CH2:58][CH2:59]2)=[O:36])[N:8]=[C:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]1[CH2:19][C:20]([F:21])([F:23])[F:22]
1
CCN(CC)CC
CS(C)=O
C1CCOC1
null
70.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
202,902
null
null
null
null
ord_dataset-19e5fc80c1554f4f8641c835e055f02b
1990-01-01T00:01:00
true
A mixture of 1.6 grams (0.004 mole) of (4-trifluoromethylsulfonyloxyphenyl)(2,3-dihydro-2,2-dimethylbenzofuran-5-yl) ketone in 75 mL of ethanol was stirred, and 0.6 mL (0.0121 mole) of hydrazine hydrate followed by 0.5 mL of acetic acid were both added via syringe. Upon completion of addition the reaction mixture was heated at reflux for 7 hours and then was allowed to cool to ambient temperature where it was stirred for 18 hours. The reaction mixture was concentrated under reduced pressure, and the residue was stirred with diethyl ether and water. The mixture was placed in a separatory funnel, and the layers were separated. The organic layer was washed with aqueous 10% sodium hydroxide solution, two portions of water, and with a saturated, aqueous solution of sodium chloride. The organic layer was concentrated under reduced pressure to yield 1.6 grams of (4-trifluoromethylsulfonyloxyphenyl)(2,3-dihydro-2,2-dimethylbenzofuran-5-yl) ketone hydrazone as an oil. The nmr spectrum was consistent with the proposed structure.
CC1(C)Cc2cc(C(=NN)c3ccc(OS(=O)(=O)C(F)(F)F)cc3)ccc2O1
null
NN
CC1(C)Cc2cc(C(=O)c3ccc(OS(=O)(=O)C(F)(F)F)cc3)ccc2O1
null
[F:1][C:2]([F:27])([F:26])[S:3]([O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([C:15]2[CH:16]=[CH:17][C:18]3[O:22][C:21]([CH3:24])([CH3:23])[CH2:20][C:19]=3[CH:25]=2)=O)=[CH:9][CH:8]=1)(=[O:5])=[O:4].O.[NH2:29][NH2:30].C(O)(=O)C>C(O)C>[F:1][C:2]([F:27])([F:26])[S:3]([O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13](=[N:29][NH2:30])[C:15]2[CH:16]=[CH:17][C:18]3[O:22][C:21]([CH3:24])([CH3:23])[CH2:20][C:19]=3[CH:25]=2)=[CH:9][CH:8]=1)(=[O:5])=[O:4]
null
CC(=O)O
CCO
O
25
null
96.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,326,429
Cc1cc(C)c(C)c(C)c1C
ClB(Cl)Cl
null
null
ord_dataset-cfad8b3f00044bcda60a96b019f09872
2013-01-01T00:08:00
true
To a solution of B4 (0.45 g, 0.1 mmol) and pentamethylbenzene (0.158 g, 1 mmol) in anhyd CH2Cl2 (30 mL) at −78° C., BCl3 (0.2 mmol) was dropwise added under N2. The reaction mixture was stirred at −78° C. and after 15-20 min the reaction was quenched with 20 mL of CHCl3/MeOH (10:1) mixture. The resulting mixture was warmed to rt. The organic solvents were evaporated under vacuum. The residues were purified by column chromatography [Silica gel 35 mm dia, 8 inch thick, EtOAc/hexanes (1:2)] to obtain B6 (0.17 g, 0.61 mmol, 61%) as brownish solid: mp 150-154° C.; TLC Rf=0.48 [EtOAc/hexanes (1:2)]; 1H NMR (CD3OD, 600 MHz) δ 7.14 (1H, d, J=8.4 Hz), 6.88 (1H, d, J=8.4 Hz), 6.53 (1H, s), 6.42 (1H, dd, J=2.4, 8.4 Hz), 6.37 (1H, d, J=2.4 Hz), 6.33 (1H, dd, J=2.4, 8.4 Hz), 6.24 (1H, d, J=1.8 Hz), 4.95 (2H, s), 3.75 (3H, s); 13C NMR (CD3OD, 150 MHz) δ 161.8, 159.1, 157.3, 155.9, 130.1, 130.0, 128.4, 121.4, 119.9, 117.6, 109.4, 106.1, 103.4, 102.4, 69.2, 55.6; Anal. (%) calcd for C16H14O4.0.1 H2O, C 70.63, H 5.26, found C 70.42, H 5.20.
COc1ccc(C2=Cc3ccc(O)cc3OC2)c(O)c1
null
COc1ccc(C2=Cc3ccc(OCc4ccccc4)cc3OC2)c(OCc2ccccc2)c1
null
null
C([O:8][C:9]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:10]=1[C:11]1[CH2:12][O:13][C:14]2[C:19]([CH:20]=1)=[CH:18][CH:17]=[C:16]([O:21]CC1C=CC=CC=1)[CH:15]=2)C1C=CC=CC=1.CC1C(C)=C(C)C(C)=C(C)C=1.B(Cl)(Cl)Cl>C(Cl)Cl>[CH3:34][O:33][C:31]1[CH:30]=[CH:29][C:10]([C:11]2[CH2:12][O:13][C:14]3[CH:15]=[C:16]([OH:21])[CH:17]=[CH:18][C:19]=3[CH:20]=2)=[C:9]([OH:8])[CH:32]=1
0.29
ClCCl
null
null
-78
null
610
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null