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
1,327,015
[K]
null
null
null
ord_dataset-cfad8b3f00044bcda60a96b019f09872
2013-01-01T00:08:00
true
Prop-2-ynyl 6-bromohexanoate (0.606 g, 2 mmol, 1 eq.) was added to a solution of phthalimide potassium salt (0.441 g, 2.4 mmol, 1.2 eq.) in 50 mL of DMF and stirred overnight under argon. CHCl3 was added to the solution flask and was transferred to a separatory funnel containing water. The aqueous layer was separated and twice extracted with CHCl3. The combined organic layers were twice extracted with water then the solvent was removed on a rotary evaporator. Remaining solvent was removed under high vacuum overnight to yield a brown oil.
C#CCOC(=O)CCCCCN1C(=O)c2ccccc2C1=O
null
C#CCOC(=O)CCCCCBr
O=C1NC(=O)c2ccccc21
null
Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9][CH2:10][C:11]#[CH:12])=[O:8].[K].[C:14]1(=[O:24])[NH:18][C:17](=[O:19])[C:16]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:15]12.C(Cl)(Cl)Cl.O>CN(C=O)C>[C:14]1(=[O:24])[N:18]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9][CH2:10][C:11]#[CH:12])=[O:8])[C:17](=[O:19])[C:16]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:15]12
8
O
ClC(Cl)Cl
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
167,208
O=P(c1ccccc1)(c1ccccc1)c1ccccc1
[Zn]
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
ord_dataset-fdef1f30cad64430bf05cf108d8004a2
1988-01-01T00:01:00
true
To a stirred mixture of triphenylphosphine (40.7 g) and zinc powder (18.5 g) in methylene chloride (250 ml) was added carbontetrabromide (45 g) at 20°-30° C. Benzhydryl 7-phenylacetamido-3-formyl-2-cephem-4-carboxylate (10 g) was added portionwise to the above reaction mixture, and the mixture was stirred for 30 minutes at room temperature. Triphenylphosphine oxide was solidified by addition of ethyl acetate to the reaction mixture and removed by filtration. The residue left by removal of the solvents was chromatographed on silica gel. The elution with chloroform containing ethyl acetate (10%) gave benzhydryl 7-phenylacetamido-3-(2,2-dibromovinyl)-2-cephem-4-carboxylate (4.4 g).
O=C(Cc1ccccc1)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)C(C=C(Br)Br)=CS[C@H]12
null
BrC(Br)(Br)Br
O=CC1=CS[C@@H]2C(NC(=O)Cc3ccccc3)C(=O)N2C1C(=O)OC(c1ccccc1)c1ccccc1
null
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([Br:24])(Br)(Br)[Br:21].[C:25]1([CH2:31][C:32]([NH:34][CH:35]2[C:60](=[O:61])[N:37]3[CH:38]([C:44]([O:46][CH:47]([C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)=[O:45])[C:39]([CH:42]=O)=[CH:40][S:41][C@H:36]23)=[O:33])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl.[Zn].C(OCC)(=O)C>[C:25]1([CH2:31][C:32]([NH:34][CH:35]2[C:60](=[O:61])[N:37]3[CH:38]([C:44]([O:46][CH:47]([C:48]4[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=4)[C:54]4[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=4)=[O:45])[C:39]([CH:42]=[C:20]([Br:24])[Br:21])=[CH:40][S:41][C@H:36]23)=[O:33])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
0.5
CCOC(C)=O
ClCCl
null
25
33.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
654,386
Cl
O=C([O-])O
[Na+]
null
ord_dataset-fe016e2f90e741a590ad77fd5933161f
2004-01-01T00:11:00
true
A mixture of (R)-3-(5-acetoxyhexyl)-1,5-dimethylpyrido[2,3-d]pyrimidine-2,4,7(1H,3H,8H)-trione (175 mg, 0.50 mmol), methanol (5 ml) and 12 M aqueous hydrochloric acid (1 ml) was stirred at room temperature for 18 hours and then treated with saturated aqueous sodium bicarbonate solution (10 ml). After concentrating under reduced pressure to remove the methanol, the aqueous mixture was extracted with ethyl acetate (20 ml). The extract was applied to a short column of silica gel and eluted with ethyl acetate to afford (R)-1,5-dimethyl-3-(5-hydroxyhexyl)pyrido[2,3-d]pyrimidine-2,4,7(1H,3H,8H)-trione (50 mg, 32% yield) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.17 (d, 3H), 1.30-1.71 (m, 6H), 2.67 (s, 3H), 3.57 (s, 3H), 3.72-3.88 (m, 1H), 3.98 (t, 2H), 6.23 (s, 1H).
Cc1cc(=O)[nH]c2c1c(=O)n(CCCC[C@@H](C)O)c(=O)n2C
null
CC(=O)O[C@H](C)CCCCn1c(=O)c2c(C)cc(=O)[nH]c2n(C)c1=O
null
null
C([O:4][C@H:5]([CH3:25])[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:15](=[O:16])[C:14]2[C:17]([CH3:22])=[CH:18][C:19](=[O:21])[NH:20][C:13]=2[N:12]([CH3:23])[C:11]1=[O:24])(=O)C.Cl.C(=O)(O)[O-].[Na+]>CO>[CH3:23][N:12]1[C:13]2[NH:20][C:19](=[O:21])[CH:18]=[C:17]([CH3:22])[C:14]=2[C:15](=[O:16])[N:10]([CH2:9][CH2:8][CH2:7][CH2:6][C@H:5]([OH:4])[CH3:25])[C:11]1=[O:24]
18
CO
null
null
25
32.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
60,950
null
null
null
null
ord_dataset-912d62c1690b4ebfbe998c0c9baf88a8
1979-01-01T00:12:00
true
From 4,5-dichloro-2-dichloromethylene-imidazole ("one-pot process"). 654 g (3 mol) of 4,5-dichloro-2-dichloromethyleneimidazole in a finely powdered form were added incrementally in the course of about one hour, to a mixture, which had been initially introduced, of 783 g (9 mol) of isopropylformamide and 162 g (9 mol) of water, while stirring and cooling slightly, whereupon the internal temperature rose to about 75° C. The reaction mixture was then heated to about 90°-110° C. for a further half hour. After cooling, the product was precipitated in water, filtered off, washed with water and dried. In this way, 566 g (85% of theory) of 4,5-dichloro-imidazole-2-carboxylic acid isopropylamide with a melting point of 150° C. were obtained.
CC(C)NC(=O)c1nc(Cl)c(Cl)[nH]1
null
ClC1=NC(=C(Cl)Cl)N=C1Cl
CC(C)NC=O
null
[Cl:1][C:2]1[C:6]([Cl:7])=[N:5][C:4](=C(Cl)Cl)[N:3]=1.[CH:11]([NH:14][CH:15]=[O:16])([CH3:13])[CH3:12].O>>[CH:11]([NH:14][C:15]([C:4]1[NH:3][C:2]([Cl:1])=[C:6]([Cl:7])[N:5]=1)=[O:16])([CH3:13])[CH3:12]
null
O
null
null
null
85
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
222,885
null
null
null
null
ord_dataset-59f453c3a3d34a89bfd97b6b8b151908
1991-01-01T00:02:00
true
Condensation between 4-benzylpiperidine (438 mg) and 2,4-dibenzyloxybenzoic acid is carried out in the same manner as in Example 4, i) to obtain 1-(2,4-dibenzyloxybenzoyl)-4-benzylpiperidine (1.0 g) in the colorless oily form.
O=C(c1ccc(OCc2ccccc2)cc1OCc1ccccc1)N1CCC(Cc2ccccc2)CC1
null
O=C(O)c1ccc(OCc2ccccc2)cc1OCc1ccccc1
c1ccc(CC2CCNCC2)cc1
null
[CH2:1]([CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:14]([O:21][C:22]1[CH:30]=[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:28]=[CH:27][C:23]=1[C:24](O)=[O:25])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[CH2:14]([O:21][C:22]1[CH:30]=[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:28]=[CH:27][C:23]=1[C:24]([N:11]1[CH2:12][CH2:13][CH:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:9][CH2:10]1)=[O:25])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=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
397,878
[K+]
[OH-]
null
null
ord_dataset-a4a191e812a64d0598ea918f047e8da7
1998-01-01T00:04:00
true
A solution of 1,8-dichloro-3, 6-dioxaoctane (40 g) and potassium hydroxide (11.8 g) in ethylene glycol (100 ml) was stirred at 100° C. for 18 h. The mixture was then cooled, filtered and the residue washed with acetone (2×35 ml). The combined filtrate was then distilled to yield the product as a clear oil (13.5 g, 30%), b.p. 120°-122° C./0.2 mm Hg; I.r. (liquid film) 3430 cm-1.
OCCOCCOCCOCCCl
null
ClCCOCCOCCCl
OCCO
null
Cl[CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][Cl:10].[OH-].[K+].[CH2:13]([OH:16])[CH2:14][OH:15]>>[Cl:10][CH2:9][CH2:8][O:7][CH2:6][CH2:5][O:4][CH2:3][CH2:2][O:15][CH2:14][CH2:13][OH:16]
null
null
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
332,283
null
null
null
null
ord_dataset-1558660634294cc8ad7e01746e9083fd
1996-01-01T00:06:00
true
More specifically, following Tetrahedron Letters, 31, 6321-6324 (1990), trifluoromethanesulfonic anhydride (4) is reacted with 1,1-bi-2-naphthol (3) to form 2,2'-bis(trifluoromethanesulfonyloxy)-1,1'-binaphthyl (5). This compound (5) is reacted with phosphine oxide (6) in the presence of a palladium catalyst to form 2-phosphinyl-2'-trifluoromethanesulfonyloxy-1,1'-binaphthyl (7). Compound (7) is then reduced in the presence of triethylamine, followed by hydrolysis of the reduction product to form 2-phosphino-2'-hydroxy-1,1'-binaphthyl (8). Further, this compound (8) is reacted with chlorophosphine (9) in the presence of triethylamine, whereby the phosphine compound (I) of the present invention is prepared.
Oc1ccc2ccccc2c1-c1c(P)ccc2ccccc12
null
O=[PH2]c1ccc2ccccc2c1-c1c(OS(=O)(=O)C(F)(F)F)ccc2ccccc12
null
null
[PH2:1]([C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]=1[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][C:14]=1[O:23]S(C(F)(F)F)(=O)=O)=O>C(N(CC)CC)C>[PH2:1][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]=1[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][C:14]=1[OH:23]
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
1,042,986
CCOC(=O)c1nc2ccccc2c(=O)[nH]1
NCc1ccnc(OCCCc2ncn(C(c3ccccc3)(c3ccccc3)c3ccccc3)n2)c1
null
null
ord_dataset-3af92aec23dc4810b92eb0d8c60023ee
2011-01-01T00:03:00
true
By a method similar to that in Example 22, and using, instead of ethyl 4-oxo-3,4-dihydro-2-quinazolinecarboxylate, ethyl 5-[3-(ethoxycarbonyl)phenyl]-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-2-carboxylate obtained in Reference Example 82 and using, instead of 1-[2-({3-[1-(triphenylmethyl)-1H-1,2,4-triazol-3-yl]propyl}oxy)pyridin-4-yl]methaneamine, 1-{3-[(2-{[1-(triphenylmethyl)-1H-1,2,4-triazol-3-yl]oxy}ethyl)oxy]phenyl}methanamine obtained in Reference Example 32, the title compound was obtained as a white powder (132.7 mg, 58%).
CCOC(=O)c1cccc(-c2csc3nc(C(=O)NCc4cccc(OCCOc5nc[nH]n5)c4)[nH]c(=O)c23)c1
null
CCOC(=O)c1cccc(-c2csc3nc(C(=O)OCC)[nH]c(=O)c23)c1
NCc1cccc(OCCOc2ncn(C(c3ccccc3)(c3ccccc3)c3ccccc3)n2)c1
null
O=C1C2C(=CC=CC=2)N=C(C(OCC)=O)N1.[CH2:17]([O:19][C:20]([C:22]1[CH:23]=[C:24]([C:28]2[C:36]3[C:35](=[O:37])[NH:34][C:33]([C:38](OCC)=[O:39])=[N:32][C:31]=3[S:30][CH:29]=2)[CH:25]=[CH:26][CH:27]=1)=[O:21])[CH3:18].C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)N2C=NC(CCCOC3C=C(CN)C=CN=3)=N2)C=CC=CC=1.C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:86]2[CH:90]=[N:89][C:88]([O:91][CH2:92][CH2:93][O:94][C:95]3[CH:96]=[C:97]([CH2:101][NH2:102])[CH:98]=[CH:99][CH:100]=3)=[N:87]2)C=CC=CC=1>>[O:37]=[C:35]1[NH:34][C:33]([C:38](=[O:39])[NH:102][CH2:101][C:97]2[CH:98]=[CH:99][CH:100]=[C:95]([O:94][CH2:93][CH2:92][O:91][C:88]3[N:89]=[CH:90][NH:86][N:87]=3)[CH:96]=2)=[N:32][C:31]2[S:30][CH:29]=[C:28]([C:24]3[CH:23]=[C:22]([CH:27]=[CH:26][CH:25]=3)[C:20]([O:19][CH2:17][CH3:18])=[O:21])[C:36]1=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
1,624,152
[Pd+2]
Cl
[OH-]
null
ord_dataset-35c51552812941cda45194a013d34bb9
2015-01-01T00:08:00
true
To a solution of (6R)-8-benzyl-6-(methoxymethyl)-N-methyl-N-(1-methylpropyl)-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepin-3-amine (297 mg) in methanol (10 mL) was added 20% Pd(OH)2/C (40 mg), and the mixture was stirred under a hydrogen atmosphere at 50° C. for 4 hr. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. To a solution of the obtained crude product in ethyl acetate (10 mL) was added a 4 N hydrogen chloride-ethyl acetate solution (220 μL), and the mixture was stirred for 1 hr. The reaction mixture was filtered, and the obtained crystals were washed with ethyl acetate to give the title compound (141 mg, 55%).
CCC(C)N(C)c1cnc2c(n1)O[C@@H](COC)CNC2
null
CCC(C)N(C)c1cnc2c(n1)O[C@@H](COC)CN(Cc1ccccc1)C2
null
null
C([N:8]1[CH2:14][C:13]2[N:15]=[CH:16][C:17]([N:19]([CH3:24])[CH:20]([CH3:23])[CH2:21][CH3:22])=[N:18][C:12]=2[O:11][C@@H:10]([CH2:25][O:26][CH3:27])[CH2:9]1)C1C=CC=CC=1.C(OCC)(=O)C.[ClH:34]>CO.[OH-].[OH-].[Pd+2]>[ClH:34].[CH3:27][O:26][CH2:25][C@H:10]1[CH2:9][NH:8][CH2:14][C:13]2[N:15]=[CH:16][C:17]([N:19]([CH3:24])[CH:20]([CH3:23])[CH2:21][CH3:22])=[N:18][C:12]=2[O:11]1
4
CO
CCOC(C)=O
null
50
null
55
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
115,567
[K+]
null
null
null
ord_dataset-d182ca8cf3f34de69c7a38343db8c930
1984-01-01T00:03:00
true
A mixture of 2-mercapto-4-(4-methoxyphenyl)-5-(4-chlorophenyl)pyrimidine* (7 g) and potassium carbonate (8 g) in 200 ml acetone was treated with methyl iodide (4.8 ml) and stirred 5 hours at room temperature. The reaction mixture was filtered and concentrated on the rotary evaporator. Chromatography on silica gel and crystallization from ethanol gave the title compound (3.4 g), m.p. 127°-130°. Infrared and H-NMR spectra were consistent with the assigned structure. MS 342 (M+).
COc1ccc(-c2nc(SC)ncc2-c2ccc(Cl)cc2)cc1
null
O=C([O-])[O-]
COc1ccc(-c2nc(S)ncc2-c2ccc(Cl)cc2)cc1
null
[SH:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[C:5]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)=[CH:4][N:3]=1.[C:23](=O)([O-])[O-].[K+].[K+].CI>CC(C)=O>[CH3:23][S:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[C:5]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)=[CH:4][N:3]=1
5
CC(C)=O
CI
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
1,324,118
C[O+](C)C
F[B-](F)(F)F
null
null
ord_dataset-cfad8b3f00044bcda60a96b019f09872
2013-01-01T00:08:00
true
4-[(3-Chloro-2-methylphenyl)carbonyl]-2-piperazinone (I131)(250 mg, 0.989 mmol) was suspended in dry Dichloromethane (DCM) (3 mL) before treating with trimethyloxonium tetrafluoroborate (185 mg, 1.187 mmol) and stirring for 16 hours at RT under argon before adding 5-methyl-1,3-thiazole-4-carbohydrazide (I123) (233 mg, 1.484 mmol) and stirring for a further 3 hours. DCM was removed by evaporation and the residue was dissolved in 1-butanol (3.00 mL) before heating at 110° C. for 4 hours then cooled to RT overnight. The reaction was worked up by diluting with DCM (50 ml) and washing with saturated sodium bicarbonate solution (50 ml). The aqueous layer was extracted with DCM (2×30 ml), the combined extracts were washed with brine (30 ml), dried (MgSO4), filtered and evaporated to afford a pale yellow cloudy gum as crude product. The product was purified on 50 g Isolera column, eluting with DCM (3CV) then 0-10% MeOH/DCM over 10CV. The desired fractions were isolated, the solvent evaporated and the residue was further purified by MDAP (formic acid method). The desired fraction was identified and the solvent evaporated to afford a white foam of desired product in 130 mg.
Cc1scnc1-c1nnc2n1CCN(C(=O)c1cccc(Cl)c1C)C2
null
Cc1c(Cl)cccc1C(=O)N1CCNC(=O)C1
Cc1scnc1C(=O)NN
null
[Cl:1][C:2]1[C:3]([CH3:17])=[C:4]([C:8]([N:10]2[CH2:15][CH2:14][NH:13][C:12](=O)[CH2:11]2)=[O:9])[CH:5]=[CH:6][CH:7]=1.F[B-](F)(F)F.C[O+](C)C.[CH3:27][C:28]1[S:32][CH:31]=[N:30][C:29]=1[C:33]([NH:35][NH2:36])=O>ClCCl>[Cl:1][C:2]1[C:3]([CH3:17])=[C:4]([C:8]([N:10]2[CH2:15][CH2:14][N:13]3[C:33]([C:29]4[N:30]=[CH:31][S:32][C:28]=4[CH3:27])=[N:35][N:36]=[C:12]3[CH2:11]2)=[O:9])[CH:5]=[CH:6][CH:7]=1
16
ClCCl
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
1,446,304
O=C([O-])O
O=C(n1ccnc1)n1ccnc1
[Na+]
null
ord_dataset-a86112d52cd54525a5e36d41f18aced2
2014-01-01T00:07:00
true
6-chloro-N2-methylpyridine-2,3-diamine (1-2) (35 g, 222 mmol) and 1,1′-Carbonyldiimidazole (63 g, 389 mmol) were added to a round bottom flask and suspended in DMF (150 mL). The solution was heated to 80° C. in an oil bath overnight. The reaction was then suspended in ethyl acetate and sodium bicarbonate. The suspension was washed with sodium bicarbonate, brine (×5), dried over sodium sulfate, filtered, and concentrated to produce the solid 5-chloro-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (1-3). MS (M+H)+: observed=184.2, calculated=184.6.
Cn1c(=O)[nH]c2ccc(Cl)nc21
null
CNc1nc(Cl)ccc1N
CN(C)C=O
null
[Cl:1][C:2]1[N:7]=C(NC)[C:5]([NH2:10])=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:23][N:24]([CH:26]=[O:27])[CH3:25]>C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[Cl:1][C:2]1[N:7]=[C:23]2[N:24]([CH3:25])[C:26](=[O:27])[NH:10][C:5]2=[CH:4][CH:3]=1
null
CCOC(C)=O
null
null
80
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
70,112
O=P(O)(O)O
null
null
null
ord_dataset-06d4002fc4d34860a0688cba690e12dc
1980-01-01T00:09:00
true
A solution of 46 grams (0.17 mol) of 3-chloro-1-methyl-7-benzoylindole in 250 ml of methoxy-ethanol and 60 ml of 70% phosphoric acid was heated at reflux under a nitrogen atmosphere for 5 hours. The solution was then cooled and diluted with 1.5 liters of water. The organic materials were extracted with methylene chloride and concentrated. The concentrated extract was chromatographed on silica gel and the product eluted with isopropyl ether. The residue obtained crystallized upon standing and was recrystallized from isopropyl alcohol to give 8.9 grams of 1-methyl-7-benzoylindolin-2-one, having a m.p. of 89°-90.5° C.
CN1C(=O)Cc2cccc(C(=O)c3ccccc3)c21
null
Cn1cc(Cl)c2cccc(C(=O)c3ccccc3)c21
COC(C)O
null
Cl[C:2]1[C:10]2[C:5](=[C:6]([C:11](=[O:18])[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:7]=[CH:8][CH:9]=2)[N:4]([CH3:19])[CH:3]=1.C[O:21]C(O)C>P(=O)(O)(O)O.O>[CH3:19][N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][C:6]=2[C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:2][C:3]1=[O:21]
null
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
1,325,376
null
null
null
null
ord_dataset-cfad8b3f00044bcda60a96b019f09872
2013-01-01T00:08:00
true
This compound was prepared from tert-butyl 3-(1H-indazol-5-yl)azetidine-1-carboxylate and 4-fluoro-3-(oxazol-4-yl)benzene-1-sulfonyl chloride by analogy to the method outlined in example 44.c, below).
CC(C)(C)OC(=O)N1CC(c2ccc3c(cnn3S(=O)(=O)c3ccc(F)c(-c4cocn4)c3)c2)C1
null
O=S(=O)(Cl)c1ccc(F)c(-c2cocn2)c1
CC(C)(C)OC(=O)N1CC(c2ccc3[nH]ncc3c2)C1
null
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]3[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11]3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][C:23]=1[C:32]1[N:33]=[CH:34][O:35][CH:36]=1>>[F:21][C:22]1[CH:27]=[CH:26][C:25]([S:28]([N:1]2[C:9]3[C:4](=[CH:5][C:6]([CH:10]4[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11]4)=[CH:7][CH:8]=3)[CH:3]=[N:2]2)(=[O:30])=[O:29])=[CH:24][C:23]=1[C:32]1[N:33]=[CH:34][O:35][CH:36]=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
1,278,481
CC(C)[Mg]Cl
null
null
null
ord_dataset-d5c54236ecd94d61aaa071461bcfc426
2013-01-01T00:04:00
true
To a solution of aminopyrazine (3.85 g, 40.5 mmol) in THF (120 mL) was added isopropylmagnesium chloride (2.0 M THF solution, 19 mL, 38 mmol) dropwise at 0° C. The resulting slurry was stirred at room temperature for 30 min. A solution of commercially available (2S,4R)-1-tert-butyl 2-methyl 4-fluoropyrrolidine-1,2-dicarboxylate (3.2 g, 12.9 mmol) in THF (10 mL) was added to the slurry. The reaction mixture was stirred at room temperature for 4 h and quenched with methanol (3 mL). After concentration in vacuo, ethyl acetate (120 mL) and 1N HCl (60 mL) were added to the residue. The organic layers were washed with 1N HCl, water, brine, and dried over Na2SO4, and filtered. Concentration gave (2S,4R)-tert-butyl 4-fluoro-2-(pyrazin-2-ylcarbamoyl)pyrrolidine-1-carboxylate 65A (4.1 g, 100%) as a colorless foam. LC/MS [M+H]+: 311; Ret time (Method F): 1.46 min.
CC(C)(C)OC(=O)N1C[C@H](F)C[C@H]1C(=O)Nc1cnccn1
null
Nc1cnccn1
COC(=O)[C@@H]1C[C@@H](F)CN1C(=O)OC(C)(C)C
null
[NH2:1][C:2]1[CH:7]=[N:6][CH:5]=[CH:4][N:3]=1.C([Mg]Cl)(C)C.[F:13][C@H:14]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C@H:16]([C:26](OC)=[O:27])[CH2:15]1>C1COCC1>[F:13][C@H:14]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[C@H:16]([C:26](=[O:27])[NH:1][C:2]2[CH:7]=[N:6][CH:5]=[CH:4][N:3]=2)[CH2:15]1
0.5
C1CCOC1
null
null
25
null
102.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
702,025
null
null
null
null
ord_dataset-bbd7e53f000345838ad4920a07a169ff
2006-01-01T00:03:00
true
Prepared from (2′-fluoro-3-{3-[3-(2-methoxymethylsulfanyl-imidazol-1-yl)-phenyl]-3-oxo-propionylamino}-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example K71) by treatment with TFA in CH2Cl2 according to the general procedure M. Obtained as a light yellow solid (100 mg).
COCSc1nccn1-c1cccc(C2=Nc3ccc(-c4ccccc4F)cc3NC(=O)C2)c1
null
COCSc1nccn1-c1cccc(C(=O)CC(=O)Nc2cc(-c3ccccc3F)ccc2NC(=O)OC(C)(C)C)c1
null
null
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])=[CH:10][C:9]=1[NH:21][C:22](=[O:41])[CH2:23][C:24]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([N:32]2[CH:36]=[CH:35][N:34]=[C:33]2[S:37][CH2:38][O:39][CH3:40])[CH:27]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[C:11]1[CH:12]=[CH:13][C:8]2[N:7]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([N:32]4[CH:36]=[CH:35][N:34]=[C:33]4[S:37][CH2:38][O:39][CH3:40])[CH:27]=3)[CH2:23][C:22](=[O:41])[NH:21][C:9]=2[CH:10]=1
null
O=C(O)C(F)(F)F
ClCCl
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
1,460,441
Cc1ccc(S(=O)(=O)O)cc1
null
null
null
ord_dataset-a86112d52cd54525a5e36d41f18aced2
2014-01-01T00:07:00
true
A mixture of 2-chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine (211 mg, 1 mmol), 6-chloro-4-methoxypyridin-3-amine (150 mg, 0.95 mmol) and para-toluenesulphonic acid (190 mg, 1 mmol) in 1,4-dioxane (2 mL) was heated at 100° C. for 1 h. The mixture was cooled and filtered, the solid was washed with dioxane and dried in vacuo to give the product as a cream coloured solid (436 mg, >100%). 1H NMR (400 MHz, DMSO): δ 9.82 (s, 1H); 8.76 (s, 1H); 8.44 (s, 2H); 7.38 (s, 1H); 4.00 (s, 3H); 2.99-2.92 (m, 3H).
CNc1nc(Nc2cnc(Cl)cc2OC)ncc1C(F)(F)F
null
COc1cc(Cl)ncc1N
CNc1nc(Cl)ncc1C(F)(F)F
null
Cl[C:2]1[N:7]=[C:6]([NH:8][CH3:9])[C:5]([C:10]([F:13])([F:12])[F:11])=[CH:4][N:3]=1.[Cl:14][C:15]1[N:20]=[CH:19][C:18]([NH2:21])=[C:17]([O:22][CH3:23])[CH:16]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[Cl:14][C:15]1[N:20]=[CH:19][C:18]([NH:21][C:2]2[N:7]=[C:6]([NH:8][CH3:9])[C:5]([C:10]([F:13])([F:12])[F:11])=[CH:4][N:3]=2)=[C:17]([O:22][CH3:23])[CH:16]=1
null
C1COCCO1
null
null
100
null
137.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
520,294
[Al+3]
[H-]
[Li+]
null
ord_dataset-262b40ea420c471da9b9244fe9b8f645
2001-01-01T00:10:00
true
Prepared according to the method described in Example 1b) from lithium aluminium hydride (41.9 ml, 1.0M solution in ether) and solution (2S)-2-(biphenyl-4-yloxy)propanoic acid, ethyl ester (11.3 g, Example 2a)) in dry tetrahydrofuran (200 ml) at 0° C. The sub-title compound obtained after work-up was used directly without further purification (9.52 g).
C[C@@H](CO)Oc1ccc(-c2ccccc2)cc1
null
CCOC(=O)[C@H](C)Oc1ccc(-c2ccccc2)cc1
null
null
[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:12]=[CH:11][C:10]([O:13][C@@H:14]([CH3:20])[C:15](OCC)=[O:16])=[CH:9][CH:8]=1>O1CCCC1>[C:7]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:8]=[CH:9][C:10]([O:13][C@@H:14]([CH3:20])[CH2:15][OH:16])=[CH:11][CH:12]=1
null
C1CCOC1
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
151,738
[H-]
[Na+]
null
null
ord_dataset-772de90433b44abbbacf9b316b845c31
1986-01-01T00:12:00
true
In a 200 ml round-bottom flask is placed a solution of 8.0 g of p-(1-imidazolylmethyl)aniline prepared as described in Reference Example 3, and 30 ml of formic acid in 80 ml of toluene. The flask was fitted with a water separator, and the solution was refluxed for 4 hours. After concentration under reduced pressure, the residual solid was recrystallized from ethanol-diethyl ether to give 6.4 g of p-(1-imidazolylmethyl)-N-formylaniline as colorless prisms. M.P.: 121°-123° C. To a suspension of 0.48 g of 50% sodium hydride in 50 ml of dry dimethylformamide was added 2.01 g of the formylaniline and mixture was heated to 100° C. A solution of 1.81 g of ethyl α-bromopropionate in 30 ml of dry dimethylformamide was added to the mixture and the reaction mixture was heated at 100° C. for 16 hours. After removal of the solvent under reduced pressure, 50 ml of dichloromethane was added to the residue, and the solution was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was chromatographed on silica gel using dichloromethane-ethanol (20:1 by volume) to give 1.58 g of N-formyl-N-[p-(1-imidazolylmethyl)phenyl]alanine ethyl ester as a pale brown oil. Then, a solution of 1.58 g of the resulting ester and 5 ml of concentrated hydrochloric acid in 50 ml of ethanol was stirred for 40 hours at room temperature. After concentration under reduced pressure, the residual solid was recrystallized from ethanol-diethyl ether to give 1.18 g of N-[p-(1-imidazolylmethyl)phenyl]alanine ethyl ester dihydrochloride as pale yellow crystals. M.P.: 154°-159° C.
CCOC(=O)[C@H](C)N(C=O)c1ccc(Cc2ncc[nH]2)cc1
null
CCOC(=O)C(C)Br
O=CNc1ccc(Cc2ncc[nH]2)cc1
null
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[C:4]1[CH2:8][C:9]1[CH:17]=[CH:16][C:12]([NH:13][CH:14]=[O:15])=[CH:11][CH:10]=1.Br[CH:19]([CH3:25])[C:20]([O:22][CH2:23][CH3:24])=[O:21]>CN(C)C=O>[CH2:23]([O:22][C:20](=[O:21])[C@H:19]([CH3:25])[N:13]([CH:14]=[O:15])[C:12]1[CH:11]=[CH:10][C:9]([CH2:8][C:4]2[NH:3][CH:7]=[CH:6][N:5]=2)=[CH:17][CH:16]=1)[CH3:24]
null
CN(C)C=O
null
null
100
52.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
92,487
O=C([O-])[O-]
[K+]
null
null
ord_dataset-dba7c8cf38834984ba5e6376158f46fe
1982-01-01T00:03:00
true
Ethyl 5-ethylthiazol-2-ylcarbamoylcarboxylate (685 mg., 3 mmoles), 1 N potassium carbonate (3 ml., 3 equivalents), water (22 ml.) and ethanol (2--3 ml.) were heated on a steam bath. After 10 minutes, dissolution was nearly complete. After an additional 15 minutes, tlc (chloroform-5% acetic acid) indicated reaction was complete. The cooled reaction mixture was filtered, and crude product (380 mg.) precipitated from the filtrate by acidification with acetic acid. Recrystallization of the crude from isopropyl alcohol gave purified 5-ethylthiazol-2-ylcarbamoylcarboxylic acid [280 mg., m.p. 206.5° C. (dec)].
CCc1cnc(NC(=O)C(=O)O)s1
null
CCOC(=O)C(=O)Nc1ncc(CC)s1
null
null
[CH2:1]([C:3]1[S:7][C:6]([NH:8][C:9]([C:11]([O:13]CC)=[O:12])=[O:10])=[N:5][CH:4]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].O.C(O)C>C(Cl)(Cl)Cl>[CH2:1]([C:3]1[S:7][C:6]([NH:8][C:9]([C:11]([OH:13])=[O:12])=[O:10])=[N:5][CH:4]=1)[CH3:2]
0.17
ClC(Cl)Cl
CCO
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
528,456
CCCC[N+](CCCC)(CCCC)CCCC
[F-]
null
null
ord_dataset-f027aa93238e424fbbf9bad1c7699adc
2001-01-01T00:12:00
true
2-Tert-butyldimethylsilyl-1-dimethylsulfamoyl imidazole (1) (4.1 g, 14.2 mmol) is taken up in 47 mL of anhydrous THF and cooled to −200° C. n-BuLi (8.9 mL, 14.2 mmol) is added dropwise to the solution of (1). The resultant solution is stirred at −20° C. for 45 min. Cyclohexylmethyl iodide (2) (3.14 g, 14 mmol) is then added dropwise to the reaction mixture. Then reaction is warmed to rt and stirred overnight. The next day the reaction is quenched with saturated ammonium chloride and diluted with water. The mixture is extracted with ethyl acetate (3×100 mL). The organic layers are combined and washed with water followed by brine. The organic phase is dried over sodium sulfate and the solvent removed under reduced pressure. Flash chromatography (4:1 ethyl acetate/hexane) affords 2.26 g (5.6 mmol) of 5-cyclohexylmethyl-2-tert-butyldimethylsilyl-1-dimethylsulfamoyl imidazole (3). (3) (2.26 g, 5.6 mmol) is taken up in 56 mL of THF and cooled to 0° C. A 1M solution of TBAF in THF (5.6 mL, 5.6 mmol) is added dropwise to the solution of (3). The reaction is warmed to rt and stirred overnight. The next day the reaction is quenched with water and then extracted with ethyl acetate. The organic layer is washed with water followed by brine. The organic phase is dried over sodium sulfate and the solvent removed under reduced pressure. Flash chromatography (1:1 ethyl acetate/hexane) affords 1.2 g (4.42 mmol) of 5-cyclohexylmethyl-1-dimethylsulfamoyl imidazole (4). (4) (1.2 g, 4.42 mmol) is taken up in 25 mL of a 1.5N HCl solution and heated at reflux for 2 h. The reaction is cool to rt and diluted with ethyl acetate. The mixture is brought to pH 13 with 2N NaOH and then extracted with chloroform (4×100 mL). The organic layers are combined and washed with water followed by brine. The organic phase is dried over sodium sulfate and the solvent removed under reduced pressure. Flash chromatography (9:1 chloroform/methanol) affords 700 mg (4.27 mmol) of 4(5)-cyclohexylmethyl-1H-imidazole (5) (J-1).
CN(C)S(=O)(=O)n1cncc1CC1CCCCC1
null
CN(C)S(=O)(=O)n1c(CC2CCCCC2)cnc1[Si](C)(C)C(C)(C)C
null
null
[CH:1]1([CH2:7][C:8]2[N:12]([S:13](=[O:18])(=[O:17])[N:14]([CH3:16])[CH3:15])[C:11]([Si](C(C)(C)C)(C)C)=[N:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(OCC)(=O)C.CCCCCC>C1COCC1>[CH:1]1([CH2:7][C:8]2[N:12]([S:13](=[O:18])(=[O:17])[N:14]([CH3:15])[CH3:16])[CH:11]=[N:10][CH:9]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
8
CCCCCC
CCOC(C)=O
C1CCOC1
0
78.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
637,204
[Pd]
O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
c1coc(P(c2ccco2)c2ccco2)c1
null
ord_dataset-a192df1b44174b5886ef2005f759d553
2004-01-01T00:05:00
true
To a stirred solution of 100 mg (0.27 mmol) (7-iodo-4-methoxy-benzothiazol-2-yl)-carbamic acid methyl ester in 3 ml dioxane were added 0.2 g (0.54 mmol) tri-n-butyl-(1-cyclohex-1-enyl)-stannane, 5.0 mg (0.009 mmol) bis(dibenzylideneacetone)palladium and 10 mg (0.043 mmol) trifurylphosphine. The mixture was heated at 100° C. for 16 h and then poured onto water and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (ethyl acetate/hexane 1:4) afforded 16 mg (7-Cyclohex-1-enyl-4-methoxy-benzothiazol-2-yl)-carbamic acid methyl ester (18%) as an off white solid; F.p.: 164-173° C.
COC(=O)Nc1nc2c(OC)ccc(C3=CCCCC3)c2s1
null
CCCC[Sn](CCCC)(CCCC)C1=CCCCC1
COC(=O)Nc1nc2c(OC)ccc(I)c2s1
null
[CH3:1][O:2][C:3](=[O:17])[NH:4][C:5]1[S:6][C:7]2[C:13](I)=[CH:12][CH:11]=[C:10]([O:15][CH3:16])[C:8]=2[N:9]=1.C([Sn](CCCC)(CCCC)[C:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]=1)CCC.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH3:1][O:2][C:3](=[O:17])[NH:4][C:5]1[S:6][C:7]2[C:13]([C:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]=3)=[CH:12][CH:11]=[C:10]([O:15][CH3:16])[C:8]=2[N:9]=1
null
C1COCCO1
null
null
100
18.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,315,454
[Fe]
[Na+]
[OH-]
null
ord_dataset-2d6edb8ffd434003bb508360153bd9bb
2013-01-01T00:07:00
true
Iron powder (0.15 g, 2.574 mmol) was added to a solution of dimethyl-(4-nitro-2-oxazol-2-yl-phenyl)-amine (200 mg, 0.86 mmol) in acetic acid (3 ml) and stirred overnight at room temperature. The reaction mixture was poured into ice water and basified with dilute sodium hydroxide solution and then filtered. The filtrate was extracted with ethyl acetate, and the organic layer was washed with water, then brine and dried. Evaporation to dryness gave N1,N1-dimethyl-2-oxazol-2-yl-benzene-1,4-diamine (150 mg, 88.2%) as oil.
CN(C)c1ccc(N)cc1-c1ncco1
null
CN(C)c1ccc([N+](=O)[O-])cc1-c1ncco1
null
null
[CH3:1][N:2]([CH3:17])[C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-])=O)=[CH:5][C:4]=1[C:12]1[O:13][CH:14]=[CH:15][N:16]=1.[OH-].[Na+]>C(O)(=O)C.[Fe]>[CH3:1][N:2]([CH3:17])[C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][C:4]=1[C:12]1[O:13][CH:14]=[CH:15][N:16]=1
8
CC(=O)O
null
null
25
85.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
198,349
null
null
null
null
ord_dataset-f6fafbb8ce5f4ef099be3a772075ec97
1989-01-01T00:10:00
true
N-Bromosuccinimide (1.3 g, 7.3 mmol) is added to a suspension of 9-(4-chlorophenyl)methylguanine (1.5 g; 5.4 mmol), Example 3, in glacial acetic acid (100 ml) and the mixture is stirred for 20 hours at room temperature. The solution is poured into water (400 ml) and the resulting precipitate is filtered, washed with water and methanol and dried. Yield: 1.0 g; mp>300° C.
Nc1nc2c(nc(Br)n2Cc2ccc(Cl)cc2)c(=O)[nH]1
null
O=C1CCC(=O)N1Br
Nc1nc2c(ncn2Cc2ccc(Cl)cc2)c(=O)[nH]1
null
[Br:1]N1C(=O)CCC1=O.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][N:17]2[CH:25]=[N:24][C:23]3[C:22](=[O:26])[NH:21][C:20]([NH2:27])=[N:19][C:18]2=3)=[CH:12][CH:11]=1.O>C(O)(=O)C>[Br:1][C:25]1[N:17]([CH2:16][C:13]2[CH:14]=[CH:15][C:10]([Cl:9])=[CH:11][CH:12]=2)[C:18]2[N:19]=[C:20]([NH2:27])[NH:21][C:22](=[O:26])[C:23]=2[N:24]=1
20
CC(=O)O
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
1,023,791
CN1CCNCC1
null
null
null
ord_dataset-136cfada6ce247b4919085a57363459e
2011-01-01T00:01:00
true
The title compound was prepared following the procedure described in the synthesis of 28a using 27d and 1-methylpiperazine. 1H-NMR (DMSO-d6) δ (ppm): 2.28 (3H, s), 2.64 (4H, brm), 3.22 (4H, brm), 7.21 (1H, m), 7.58 (1H, m), 7.79 (3H, m), 8.67 (1H, m). m/z 384.2
CN1CCN(c2cc3[nH]cc4c(=O)n(-c5ccsc5)nc-4c3cc2F)CC1
null
O=c1c2c[nH]c3cc(F)c(F)cc3c-2nn1-c1ccsc1
O=c1c2c[nH]c3cc(N4CCNCC4)c(F)cc3c-2nn1-c1ccccc1
null
FC1[C:11]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=CC2NC=C3C(=O)N(C4C=CC=CC=4)N=C3C=2C=1.F[C:29]1[C:30]([F:48])=[CH:31][C:32]2[C:33]3[C:34]([C:39](=[O:47])[N:40]([C:42]4[CH:46]=[CH:45][S:44][CH:43]=4)[N:41]=3)=[CH:35][NH:36][C:37]=2[CH:38]=1.CN1CCNCC1>>[F:48][C:30]1[C:29]([N:15]2[CH2:16][CH2:17][N:12]([CH3:11])[CH2:13][CH2:14]2)=[CH:38][C:37]2[NH:36][CH:35]=[C:34]3[C:39](=[O:47])[N:40]([C:42]4[CH:46]=[CH:45][S:44][CH:43]=4)[N:41]=[C:33]3[C:32]=2[CH:31]=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
849,553
[K+]
null
null
null
ord_dataset-171b840ae6e84e45bab43b987d09f5c7
2008-01-01T00:11:00
true
3,4-Dihydroxy-benzaldehyde (2.1 g, 0.015 mol), K2CO3 (4.0 g, 0.03 mol) and 1-iodohexane (6.4 g, 0.03 mol) were stirred in 100 ml of 1-butanol under reflux for 24 h. After cooling, the 1-butanol was removed by rotary evaporation. The residue was dissolved in 200 ml of ether, washed with water (dist.) and brine. The solution was dried over Na2SO4 and the solvent was removed to yield 3.7 g 3,4-Bis-hexyloxy-benzaldehyde (85%) as a dark solid. 1H NMR (400 MHz, CDCl3): δ 9.83 (s, 1H), 7.41 (m, 2H), 6.95 (d, 1H, J=8.5 Hz), 4.07 (m, 4H), 1.85 (m, 4H), 1.48 (m, 4H), 1.35 (m, 8H), 0.91 (m, 6H).
CCCCCCOc1ccc(C=O)cc1OCCCCCC
null
O=Cc1ccc(O)c(O)c1
CCCCCCI
O=C([O-])[O-]
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1O)[CH:5]=[O:6].[C:11]([O-:14])([O-])=O.[K+].[K+].I[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]>C(O)CCC>[CH2:18]([O:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:14][CH2:11][CH2:8][CH2:9][CH2:2][CH2:3][CH3:4])[CH:5]=[O:6])[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
null
CCCCO
null
null
null
161
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,390,937
null
null
null
null
ord_dataset-31641fb65b34430fa7435229b949b604
2014-01-01T00:01:00
true
The title compound was prepared in the same manner as described in example 21 from 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (23 mg, 0.062 mmol), ethanol (0.7 mL), and dimethylamine (0.461 mL, 0.923 mmol). The product was dried in vacuum oven at 50° C. for 5 hr and collected as 0.016 g (67%). LCMS E-S (M+H)=383.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.44 (d, J=6.57 Hz, 6H), 2.05-2.25 (m, 6H), 3.14 (s, 6H), 4.34 (d, J=4.80 Hz, 2H), 4.99 (dt, J=13.39, 6.69 Hz, 1H), 5.89 (s, 1H), 6.94 (s, 1H), 7.96 (s, 1H), 8.64 (t, J=4.93 Hz, 1H), 11.56 (br. s., 1H).
Cc1cc(C)c(CNC(=O)c2cc(N(C)C)nc3c2cnn3C(C)C)c(=O)[nH]1
null
Cc1cc(C)c(CNC(=O)c2cc(Cl)nc3c2cnn3C(C)C)c(=O)[nH]1
CNC
null
Cl[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.[CH3:27][NH:28][CH3:29]>C(O)C>[CH3:27][N:28]([CH3:29])[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1
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
256,576
BrCc1ccc(-c2ccccc2-c2nnn(C(c3ccccc3)(c3ccccc3)c3ccccc3)n2)cc1
null
null
null
ord_dataset-30ad5cf6083a45a387b45bebad1a4d65
1992-01-01T00:10:00
true
Substituting ethyl butyrylacetate for ethyl 3-oxooctanoate and 4-bromobenzyl bromide for 4-bromomethyl-2'-(2-(triphenylmethyl)tetrazol-5-yl)-biphenyl in Example 4 gave the title compound.
CCCC(=O)C(Cc1ccc(Br)cc1)C(=O)OCC
null
BrCc1ccc(Br)cc1
CCCCCC(=O)CC(=O)OCC
null
[O:1]=[C:2]([CH2:9][CH2:10][CH2:11]CC)[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[Br:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Br)=[CH:17][CH:16]=1.BrCC1C=CC(C2C=CC=CC=2C2N=NN(C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)N=2)=CC=1>>[Br:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][CH:3]([C:2](=[O:1])[CH2:9][CH2:10][CH3:11])[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:17][CH:16]=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
621,675
O=S(=O)(O)O
[Na+]
[OH-]
null
ord_dataset-c9f990dde2dc45d0948ecbe037a0d819
2004-01-01T00:01:00
true
A mixture of 5-bromo-2-(1-hydroxy-1-methylethyl) pyridine N-oxide from step 2 of example 30 (1.29 g) and 25% aqueous sulfuric acid was heated at 130° C. for 2 days. After cooling, the mixture was made slightly basic using ION aqueous sodium hydroxide and partitioned between ethyl acetate and water. The crude product from evaporation of the organic phase was used as such in step 2.
C=C(C)c1ccc(Br)c[n+]1[O-]
null
CC(C)(O)c1ccc(Br)c[n+]1[O-]
null
null
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:9](O)([CH3:11])[CH3:10])=[N+:6]([O-:8])[CH:7]=1.S(=O)(=O)(O)O.[OH-].[Na+]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([CH3:11])=[CH2:10])=[N+:6]([O-:8])[CH:7]=1
null
null
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
554,869
null
null
null
null
ord_dataset-ec9decb576c4424c9685993f6262bd9c
2002-01-01T00:07:00
true
The procedures of Example 1-(1) were followed, except for replacing the ethyl isocyanoacetate with 9.9 g (0.1 mol) of methyl isocyanoacetate, to obtain 15.4 g (0.055 mol 61.5% based on the 2-methoxy-4-nitrobenzoic acid) of the title compound.
COC(=O)c1ncoc1-c1ccc([N+](=O)[O-])cc1OC
null
COc1cc([N+](=O)[O-])ccc1C(=O)O
[C-]#[N+]CC(=O)OC
null
[N+:1]([CH2:3][C:4]([O:6][CH3:7])=[O:5])#[C-:2].[CH3:8][O:9][C:10]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:11]=1[C:12](O)=[O:13]>>[CH3:8][O:9][C:10]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:11]=1[C:12]1[O:13][CH:2]=[N:1][C:3]=1[C:4]([O:6][CH3:7])=[O: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
678,753
Cl
null
null
null
ord_dataset-50cdc205280641d2a3e264f32908e3d0
2005-01-01T00:07:00
true
2 mL of an 6 N aqueous solution of hydrochloride were added to the mixture of tert-butyl N-(3-{3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-azetanyl}-3-oxopropyl)-N-(2-hydroxyethyl)carbamate (0.040 g, 0.000070 mol). in acetone (5 mL). The mixture was stirred at 45° C. for 1.5 hours. The solvent was removed under removed pressure. Water (10 mL) was added to the residue, the mixture was lyophilized. The residue was purified by RP-HPLC (Hypersilprep HS C18, 8 μm, 250×21.1 mm; 5%-100% over 35 min with 0.1 M ammonium acetate, 21 mL/min) to yield 1-{3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-azetanyl}-3-[(2-hydroxyethyl)amino]-1-propanone (0.003 g, 0.00001 mol).
Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)nn2C1CN(C(=O)CCNCCO)C1
null
CC(C)(C)OC(=O)N(CCO)CCC(=O)N1CC(n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
null
null
Cl.[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]2[N:9]([CH:25]3[CH2:28][N:27]([C:29](=[O:43])[CH2:30][CH2:31][N:32]([CH2:40][CH2:41][OH:42])C(=O)OC(C)(C)C)[CH2:26]3)[N:10]=[C:11]([C:12]3[CH:17]=[CH:16][C:15]([O:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:14][CH:13]=3)[C:4]=12>CC(C)=O>[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]2[N:9]([CH:25]3[CH2:26][N:27]([C:29](=[O:43])[CH2:30][CH2:31][NH:32][CH2:40][CH2:41][OH:42])[CH2:28]3)[N:10]=[C:11]([C:12]3[CH:13]=[CH:14][C:15]([O:18][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[CH:16][CH:17]=3)[C:4]=12
1.5
CC(C)=O
null
null
45
null
14.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,677,953
[K+]
null
null
null
ord_dataset-3953983e052a4076aa7cc0880b79cb8b
2016-01-01T00:01:00
true
To the stirred solution of (R)-4-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (5.0 g, 26.3 mmol), K2CO3 (10.90 g, 79 mmol) and methyl iodide (6.58 ml, 105 mmol) was added in DMF (50 mL) and stirred for overnight at 25° C. Water was added (130 mL) and extracted with ethyl acetate (2×30 mL). The organic phase was washed with aq. Sodium bicarbonate solution (2×20 mL), dried over Na2SO4 and filtered. The clear organic phase was evaporated in vacuo to get title compound (4.5 g) m/z 204.09.
COC(=O)[C@H]1CC(=O)c2ccccc2C1
null
O=C([O-])[O-]
O=C1C[C@H](C(=O)O)Cc2ccccc21
null
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][C@@H:4]([C:12]([OH:14])=[O:13])[CH2:3]1.[C:15]([O-])([O-])=O.[K+].[K+].CI.O>CN(C=O)C>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][C@@H:4]([C:12]([O:14][CH3:15])=[O:13])[CH2:3]1
8
CN(C)C=O
O
CI
25
null
83.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
172,489
O=C([O-])[O-]
[K+]
null
null
ord_dataset-7860c6f563014da8948ede63b7110bde
1988-01-01T00:05:00
true
73 parts by weight of potassium 3-cresolate, 107 parts by weight of 3,4-dichlorobenzotrifluoride and 6.9 parts by weight of potassium carbonate in 500 parts by volume of dimethylsulfoxide were stirred at 140° C. for 8 hours. The reaction mixture was cooled to room temperature and was poured into 2,000 parts by volume of water. The oily residue was taken up in ether, and the organic phase was dried with magnesium sulfate, filtered, and concentrated under reduced pressure. Fractional distillation gave 120 parts by weight (84% of theory) of 3-(2'-chloro-4'-trifluoromethylphenoxy)-toluene of boiling point 91°-96° C./0.1 bar and refractive index nD25 : 1.5268.
Cc1cccc(Oc2ccc(C(F)(F)F)cc2Cl)c1
null
FC(F)(F)c1ccc(Cl)c(Cl)c1
Cc1cccc(O)c1C(=O)[O-]
null
[C:1]1(C([O-])=O)[C:2]([CH3:8])=[CH:3][CH:4]=[CH:5][C:6]=1[OH:7].[K+].[Cl:13][C:14]1[CH:15]=[C:16]([C:21]([F:24])([F:23])[F:22])[CH:17]=[CH:18][C:19]=1Cl.C(=O)([O-])[O-].[K+].[K+].CS(C)=O>CCOCC.O>[Cl:13][C:14]1[CH:15]=[C:16]([C:21]([F:22])([F:23])[F:24])[CH:17]=[CH:18][C:19]=1[O:7][C:6]1[CH:1]=[C:2]([CH3:8])[CH:3]=[CH:4][CH:5]=1
null
CS(C)=O
CCOCC
O
25
null
84
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
840,304
null
null
null
null
ord_dataset-074f86301ec5441ab3b52d902ac06949
2008-01-01T00:09:00
true
To a solution of [6-(2-cyano-vinyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-carbamic acid tert-butyl ester (2.7 g, 9.05 mmol) in DCM (40 mL) was added TFA (15 mL). The resulting mixture was stirred at RT for 1 h. Solvent was removed. The residue was redissolved in EtOAc. The organic layer was washed with sat. NaHCO3, H2O, brine, dried over MgSO4 and removed solvent. The crude product was purified by chromatography on silica gel. Elution with CH2Cl2:MeOH (2M NH3) mixture (97:3) gave final compound (1.6 g, 89%). MS m/z: 199.3 (M+H). Calc'd. for C13H14N2-198.26.
N#CC=Cc1ccc2c(c1)CCCC2N
null
CC(C)(C)OC(=O)NC1CCCc2cc(C=CC#N)ccc21
null
null
C(OC(=O)[NH:7][CH:8]1[C:17]2[C:12](=[CH:13][C:14]([CH:18]=[CH:19][C:20]#[N:21])=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][CH:8]1[CH2:9][CH2:10][CH2:11][C:12]2[CH:13]=[C:14]([CH:18]=[CH:19][C:20]#[N:21])[CH:15]=[CH:16][C:17]1=2
1
ClCCl
O=C(O)C(F)(F)F
null
25
null
89.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
28,365
O=C(n1ccnc1)n1ccnc1
null
null
null
ord_dataset-2cb52357eb5f43c2be56ad5c0662f18f
1977-01-01T00:08:00
true
To a solution of 360 mg. of 1,1'-carbonyldiimidazole in 6 ml. of dry tetrahydrofuran at 140° C. is added dropwise 500 mg. of 3-carboxy-4-oxo-4H-pyrimido[2,1-b]benzothiazole in 6 ml. of dry dimethylformamide. After heating for 3 hrs., 186 mg. of 5-aminotetrazole is added, and the heating maintained for an additional 15 min. The reaction mixture is cooled and the precipitated product filtered. Recrystallization from dimethylformamide gives 200 mg. of the desired product, m.p. 330°-332° C.
O=C(Nc1nnn[nH]1)c1cnc2sc3ccccc3n2c1=O
null
Nc1nnn[nH]1
O=C(O)c1cnc2sc3ccccc3n2c1=O
null
C(N1C=CN=C1)(N1C=CN=C1)=O.O1CCCC1.[C:18]([C:21]1[C:29](=[O:30])[N:28]2[C:24]([S:25][C:26]3[CH:34]=[CH:33][CH:32]=[CH:31][C:27]=32)=[N:23][CH:22]=1)([OH:20])=O.[NH2:35][C:36]1[NH:40][N:39]=[N:38][N:37]=1>CN(C)C=O>[NH:37]1[C:36]([NH:35][C:18]([C:21]2[C:29](=[O:30])[N:28]3[C:24]([S:25][C:26]4[CH:34]=[CH:33][CH:32]=[CH:31][C:27]=43)=[N:23][CH:22]=2)=[O:20])=[N:40][N:39]=[N:38]1
null
CN(C)C=O
C1CCOC1
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
894,998
null
null
null
null
ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded
2009-01-01T00:08:00
true
A mixture of 0.112 g (0.252 mmol) of 3-azido-N-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-4,5-dimethyl-benzamide and 0.069 mL (0.756 mmol) of methyl propiolate was stirred in 0.5 mL of DMA at 110° C. overnight. The vial was cooled to room temperature, and the contents were poured into stirring water. The precipitate was collected and chromatographed (10-60% EtOAc in hexanes). Fractions containing predominantly the major product were collected and further purified by precipitating from dichloromethane with hexanes to provide 57 mg of a white powder. The filtrate was combined with the mixed fractions from the first chromatography, and the resulting mixture was chromatographed again to provide 22 mg of the title compound as a pale yellow solid for a total yield of 79 mg (0.149 mmol; 59%), mp: 199° C. ESI MS (m/z 528, 100, M−H).
COC(=O)c1cn(-c2cc(C(=O)Nc3cc(C(C)(C)C)cc(NS(C)(=O)=O)c3OC)cc(C)c2C)nn1
null
C#CC(=O)OC
COc1c(NC(=O)c2cc(C)c(C)c(N=[N+]=[N-])c2)cc(C(C)(C)C)cc1NS(C)(=O)=O
null
[N:1]([C:4]1[CH:5]=[C:6]([CH:27]=[C:28]([CH3:31])[C:29]=1[CH3:30])[C:7]([NH:9][C:10]1[CH:15]=[C:14]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:13]=[C:12]([NH:20][S:21]([CH3:24])(=[O:23])=[O:22])[C:11]=1[O:25][CH3:26])=[O:8])=[N+:2]=[N-:3].[C:32]([O:36][CH3:37])(=[O:35])[C:33]#[CH:34].O>CC(N(C)C)=O>[CH3:37][O:36][C:32]([C:33]1[N:3]=[N:2][N:1]([C:4]2[CH:5]=[C:6]([C:7](=[O:8])[NH:9][C:10]3[CH:15]=[C:14]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:13]=[C:12]([NH:20][S:21]([CH3:24])(=[O:22])=[O:23])[C:11]=3[O:25][CH3:26])[CH:27]=[C:28]([CH3:31])[C:29]=2[CH3:30])[CH:34]=1)=[O:35]
null
O
CC(=O)N(C)C
null
25
42.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,545,951
null
null
null
null
ord_dataset-cac8df8aff894288876df4e093c9877f
2015-01-01T00:02:00
true
To a suspension of 6-((1H-benzo[d]imidazol-1-yl)methyl)-2-bromobenzo[d]thiazole from Step 1 of Example 1 (34.4 mg, 0.1 mmol) in DMA (3 mL) were added DIEA (15 mg, 0.12 mmol) and (1R,2R)-2-aminocyclohexanol (13.8 mg, 0.12 mmol) at rt. The reaction mixture was stirred in a sealed tube at 120° C. overnight. After cooling to rt, the mixture was concentrated under reduced pressure. The crude product was purified by preparative HPLC using a mixture of water (containing 5% CH3CN, 0.05% HCOOH) and CH3CN (containing 0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C-18 column as the stationary phase to afford (1R,2R)-2-((6-((1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (22 mg, 58%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.40 (s, 1H), 7.99 (d, J=7.3 Hz, 1H), 7.60-7.72 (m, 2H), 7.55 (dd, J=2.6, 6.0 Hz, 1H), 7.26-7.34 (m, 1H), 7.12-7.25 (m, 3H), 5.47 (s, 2H), 4.76 (br s, 1H), 3.26-3.39 (m, 2H), 2.03 (d, J=10.0 Hz, 1H), 1.87 (d, J=9.4 Hz, 1H), 1.62 (d, J=4.7 Hz, 2H), 1.03-1.39 (m, 4H). LCMS (ESI) m/z 379 (M+H)+.
O[C@@H]1CCCC[C@H]1Nc1nc2ccc(Cn3cnc4ccccc43)cc2s1
null
N[C@@H]1CCCC[C@H]1O
Brc1nc2ccc(Cn3cnc4ccccc43)cc2s1
null
[N:1]1([CH2:10][C:11]2[CH:20]=[CH:19][C:14]3[N:15]=[C:16](Br)[S:17][C:13]=3[CH:12]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.CCN(C(C)C)C(C)C.[NH2:30][C@@H:31]1[CH2:36][CH2:35][CH2:34][CH2:33][C@H:32]1[OH:37]>CC(N(C)C)=O>[N:1]1([CH2:10][C:11]2[CH:20]=[CH:19][C:14]3[N:15]=[C:16]([NH:30][C@@H:31]4[CH2:36][CH2:35][CH2:34][CH2:33][C@H:32]4[OH:37])[S:17][C:13]=3[CH:12]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1
8
CCN(C(C)C)C(C)C
CC(=O)N(C)C
null
120
null
58.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,658,040
O=C([O-])[O-]
[K+]
null
null
ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0
2015-01-01T00:11:00
true
A solution of 3-fluoro-4-hydroxy-5-methoxy-benzaldehyde (250 mg, 1.5 mmol) in DMF (2.5 mL) was treated with potassium carbonate (812 mg, 5.9 mmol) and stirred for 30 minutes. 2-Iodopropane (500 mg, 2.9 mmol) was added over 10 minutes and reaction mixture was stirred for 20 hours. The reaction mixture was partitioned between EtOAc and saturated aqueous sodium chloride solution. The organic layer was washed with saturated sodium bicarbonate solution. The organic layer was separated and dried over sodium sulfate, filtered and concentrated in vacuo to give 3-fluoro-4-isopropoxy-5-methoxybenzaldehyde. To the aldehyde was added tert-butanol (6.7 mL) and 2-methylbut-2-ene (4 mL, 38.2 mmol) and the reaction mixture was cooled to 0° C. A solution of chlorite (345 mg, 3.8 mmol) and sodium dihydrogen phosphate hydrate (527 mg, 3.8 mmol) in water (6.7 mL) was added dropwise over 5 minutes, and the reaction mixture was stirred 30 minutes. The reaction mixture was warmed to room temperature and stirred for 12 hours. The reaction mixture was basified with 1 N NaOH solution and extracted with ethyl acetate (2×50 mL). The aqueous layer was acidified with 1 N HCl solution and extracted with EtOAc (4×50 mL). The combined organics were dried (Na2SO4), filtered, and concentrated in vacuo to afford 3-fluoro-4-isopropoxy-5-methoxy-benzoic acid (190 mg, 56%) as a white solid. ESI-MS m/z calc. 228.0. found 229.3 (M−1)+; Retention time: 1.57 minutes (3 min run).
COc1cc(C=O)cc(F)c1OC(C)C
null
CC(C)I
COc1cc(C=O)cc(F)c1O
null
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:11][CH3:12])[C:9]=1[OH:10])[CH:5]=[O:6].C(=O)([O-])[O-].[K+].[K+].I[CH:20]([CH3:22])[CH3:21]>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:11][CH3:12])[C:9]=1[O:10][CH:20]([CH3:22])[CH3:21])[CH:5]=[O:6]
0.5
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
896,868
null
null
null
null
ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded
2009-01-01T00:08:00
true
Similar procedure as described in example 273 was used, starting from (1-chloro-5,6-dimethoxy-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine and 4-amino-benzonitrile to give 4-[3-(5-methyl-1H-pyrazol-3-ylamino)-5,6-dimethoxy-isoquinolin-1-ylamino]-benzonitrile. LC-MS m/e 401(MH+).
COc1ccc2c(Nc3ccc(C#N)cc3)nc(Nc3cc(C)[nH]n3)cc2c1OC
null
N#Cc1ccc(N)cc1
COc1ccc2c(Cl)nc(Nc3cc(C)[nH]n3)cc2c1OC
null
Cl[C:2]1[C:11]2[C:6](=[C:7]([O:14][CH3:15])[C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH:16][C:17]2[CH:21]=[C:20]([CH3:22])[NH:19][N:18]=2)[N:3]=1.[NH2:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=1>>[CH3:22][C:20]1[NH:19][N:18]=[C:17]([NH:16][C:4]2[N:3]=[C:2]([NH:23][C:24]3[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=3)[C:11]3[C:6]([CH:5]=2)=[C:7]([O:14][CH3:15])[C:8]([O:12][CH3:13])=[CH:9][CH:10]=3)[CH:21]=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
1,438,508
Cl
null
null
null
ord_dataset-275a3da8f45f4536ad29727f0ef9ba66
2014-01-01T00:06:00
true
Methyl 2-(3-fluorophenyl)-2-(piperidin-1-yl)acetate (224 mg, 0.89 mmol) and 37% HCl (813 μl, 26.7 mmol) were dissolved in dioxane (3 ml) and stirred under microwave irradiation at 100° C. for 6 hours. The solvents were evaporated and the residue was triturated with Et2O and sonicated. The solid was collected by suction filtration, washed with Et2O and dried under vacuum overnight to collect 2-(3-fluorophenyl)-2-(piperidin-1-yl)acetic acid hydrochloride (230 mg, 94% yield).
O=C(O)C(c1cccc(F)c1)N1CCCCC1
null
COC(=O)C(c1cccc(F)c1)N1CCCCC1
null
null
[F:1][C:2]1[CH:3]=[C:4]([CH:8]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[C:9]([O:11]C)=[O:10])[CH:5]=[CH:6][CH:7]=1.[ClH:19]>O1CCOCC1>[ClH:19].[F:1][C:2]1[CH:3]=[C:4]([CH:8]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[C:9]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=1
6
C1COCCO1
null
null
100
null
94.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
493,534
[H-]
[Na+]
null
null
ord_dataset-3f9174c7efcb4f31becbd3516cde9572
2001-01-01T00:02:00
true
Sodium hydride (60% suspension in oil, 1.2 g, 30.15 mmol) was washed with hexane, dried under nitrogen and resuspended in dry dimethylformamide (110 mL). Neat 3-methylpyrazole (2.47 g, 30.15 mmol) was added dropwise at 0° C. After the gas evolution subsided the cooling bath was removed and stirring was continued at room temperature. The [2-bromo-4-fluorophenyl]-(5,11-dihydro-pyrido [2,3-b][1,5]benzodiazepin-6-yl)-methanone of Step B (6 g, 18.07 mmol) was added in one portion to the clear solution. The mixture was placed in an oil bath (preheated at 130° C.) for 40 minutes, cooled and partitioned between water and ethyl acetate. The organic extracts were dried over magnesium sulfate and evaporated to dryness. The crude material was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with a hexane-ethyl acetate gradient (from 95:5 to 75:25) provided the less polar title compound (3.87 g) along with a mixture of 3- and 5-methylpyrazole regioisomers (0.860 g). The title compound (3.5 g, 51%) crystallized by sonication from hexane-ethanol, m.p. 208-209° C. (dec).
Cc1ccn(-c2ccc(C(=O)N3Cc4cccnc4Nc4ccccc43)c(Br)c2)n1
null
O=C(c1ccc(F)cc1Br)N1Cc2cccnc2Nc2ccccc21
Cc1cc[nH]n1
null
[H-].[Na+].[CH3:3][C:4]1[CH:8]=[CH:7][NH:6][N:5]=1.[Br:9][C:10]1[CH:15]=[C:14](F)[CH:13]=[CH:12][C:11]=1[C:17]([N:19]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[NH:23][C:22]2[N:30]=[CH:31][CH:32]=[CH:33][C:21]=2[CH2:20]1)=[O:18]>CCCCCC>[Br:9][C:10]1[CH:15]=[C:14]([N:6]2[CH:7]=[CH:8][C:4]([CH3:3])=[N:5]2)[CH:13]=[CH:12][C:11]=1[C:17]([N:19]1[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[NH:23][C:22]2[N:30]=[CH:31][CH:32]=[CH:33][C:21]=2[CH2:20]1)=[O:18]
0.67
CCCCCC
null
null
null
null
46.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,599,506
Cl[Pd]Cl
null
null
null
ord_dataset-e8c6a25568b64529b960953990e6921f
2015-01-01T00:06:00
true
Into a 100-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 7-(benzyloxy)-4-bromo-2,3-dihydro-1H-inden-1-one (520 mg, 1.64 mmol, 1.00 equiv), ethyl prop-2-enoate (825 mg, 8.24 mmol, 5.03 equiv), PdCl2 (58 mg, 0.33 mmol, 0.200 equiv), DIEA (1.06 g, 8.20 mmol, 5.00 equiv), (o-Tol)3P (201 mg, 0.66 mmol, 0.400 equiv), N,N-dimethylformamide (15 mL). The resulting solution was stirred for overnight at 90° C. in an oil bath. The reaction progress was monitored by TLC (ethyl acetate/petroleum ether=1:2). The resulting solution was diluted with 20 mL of H2O. The resulting solution was extracted with 3×15 mL of ethyl acetate and the organic extracts were combined. The resulting mixture was washed with 1×15 mL of water and 1×15 mL of aqueous saturated sodium chloride solution. The mixture was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was applied to a silica gel column, eluting with ethyl acetate/petroleum ether (1:4). This resulted in 500 mg (86%) of ethyl (2E)-3-[7-(benzyloxy)-1-oxo-2,3-dihydro-1H-inden-4-yl]prop-2-enoate as a red solid.
CCOC(=O)/C=C/c1ccc(OCc2ccccc2)c2c1CCC2=O
null
O=C1CCc2c(Br)ccc(OCc3ccccc3)c21
C=CC(=O)OCC
null
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12](Br)=[C:13]2[C:17]=1[C:16](=[O:18])[CH2:15][CH2:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]([O:24][CH2:25][CH3:26])(=[O:23])[CH:21]=[CH2:22].CCN(C(C)C)C(C)C.CN(C)C=O>O.Cl[Pd]Cl>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12](/[CH:22]=[CH:21]/[C:20]([O:24][CH2:25][CH3:26])=[O:23])=[C:13]2[C:17]=1[C:16](=[O:18])[CH2:15][CH2:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
8
O
CCN(C(C)C)C(C)C
CN(C)C=O
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
420,109
null
null
null
null
ord_dataset-94e21e9990034c729ea727e7d2ab0eb0
1998-01-01T00:12:00
true
3-[4-[N,N-Bis(2-chloroethyl)amino]phenyl]propionic acid (0.24 g; 0.83 mmol) was dissolved in 5 ml of 1,2-dichloroethane, followed by the dropwise addition of 0.22 ml (2.58 mmol; 3.1 equivalents) of oxalyl chloride (with ice-cooling from an intermediary time point due to violent exotherm). After completion of the dropwise addition, the temperature of the resultant mixture was allowed to rise again to room temperature, at which the mixture was stirred for 3 hours and then allowed to stand overnight. The mixture was thereafter concentrated under reduced pressure, whereby the title compound was obtained in a crude form. The crude compound was provided for use in the next reaction without purification.
O=C(Cl)CCc1ccc(N(CCCl)CCCl)cc1
null
O=C(Cl)C(=O)Cl
O=C(O)CCc1ccc(N(CCCl)CCCl)cc1
null
[Cl:1][CH2:2][CH2:3][N:4]([C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]([OH:18])=O)=[CH:10][CH:9]=1)[CH2:5][CH2:6][Cl:7].C(Cl)(=O)C([Cl:22])=O>ClCCCl>[Cl:1][CH2:2][CH2:3][N:4]([C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]([Cl:22])=[O:18])=[CH:10][CH:9]=1)[CH2:5][CH2:6][Cl:7]
3
ClCCCl
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
378,584
[Li]CCCC
null
null
null
ord_dataset-846d411edee44814931e062174d7ef12
1997-01-01T00:09:00
true
To a stirred solution of 4-(2-propyl)-oxazolidine-2-one in anhydrous tetrahydrofuran (250 ml) under a nitrogen atmosphere at -78° C. was added in a dropwise fashion a solution of n-butyllithium in hexane (50 ml, 77.4 mmol) over 5 to 10 min. After stirring an additional 20 min at -78° C., 4-methylpentanoyl chloride (85.2 mmol) was added neat. The reaction was warmed to room temperature and stirred 1 to 2 h at the temperature. The reaction was quenched by adding 100 ml of saturated aqueous ammonium chloride and the volatiles were removed by rotary evaporation. The resulting aqueous residue was extracted three times with ether and the combined organic phases were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. Recrystallization from hexanes/ethyl acetate provided the desired compound.
CC(C)CCC(=O)N1C(=O)OC[C@@H]1C(C)C
null
CC(C)C1COC(=O)N1
CC(C)CCC(=O)Cl
null
[CH3:1][CH:2]([CH:4]1[CH2:8][O:7][C:6](=[O:9])[NH:5]1)[CH3:3].C([Li])CCC.CCCCCC.[CH3:21][CH:22]([CH3:28])[CH2:23][CH2:24][C:25](Cl)=[O:26]>O1CCCC1>[CH3:21][CH:22]([CH3:28])[CH2:23][CH2:24][C:25]([N:5]1[C@@H:4]([CH:2]([CH3:3])[CH3:1])[CH2:8][O:7][C:6]1=[O:9])=[O:26]
0.33
C1CCOC1
CCCCCC
null
-78
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,199,753
null
null
null
null
ord_dataset-fb72428f30234761b4216139dc228d0c
2012-01-01T00:09:00
true
The title compound was prepared following procedure described for intermediate B1, but starting from 5-(3-furyl)[1,2,4]triazolo[1,5-a]pyridin-2-amine ((A2), 660 mg; 0.30 mmol; 1.0 eq.) and methoxyacetyl chloride (65 mg, 0.60 mmol; 2.0 eq.) as a white powder (59 mg, 72%). HPLC, Rt: 2.21 min. (purity 98.2%). LC/MS, M+(ESI): 273.4, M−(ESI): 271.4.
COCC(=O)Nc1nc2cccc(-c3ccoc3)n2n1
null
COCC(=O)Cl
Nc1nc2cccc(-c3ccoc3)n2n1
null
[O:1]1[CH:5]=[CH:4][C:3]([C:6]2[N:11]3[N:12]=[C:13]([NH2:15])[N:14]=[C:10]3[CH:9]=[CH:8][CH:7]=2)=[CH:2]1.[CH3:16][O:17][CH2:18][C:19](Cl)=[O:20]>>[O:1]1[CH:5]=[CH:4][C:3]([C:6]2[N:11]3[N:12]=[C:13]([NH:15][C:19](=[O:20])[CH2:18][O:17][CH3:16])[N:14]=[C:10]3[CH:9]=[CH:8][CH:7]=2)=[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
229,627
null
null
null
null
ord_dataset-9adbd9cd2fd941f7af27fb31c9bf3bac
1991-01-01T00:06:00
true
A mixture of 1.44 g of 8-(p-chlorophenylsulfonamido-4-[3-(3-pyridyl)-propyl]-octanamide and 0.52 mL pyridine in 5.8 mL dioxane is cooled to 0° C. and 0.51 mL trifluoroacetic anhydride is added over a period of 1 hour. The mixture is then stirred at room temperature for 3 hours. The reaction is quenched by the addition of saturated aqueous sodium bicarbonate solution and extracted with methylene chloride (2×20 mL). The combined organic extracts are dried, filtered and evaporated to give 8-(p-chlorophenyl- sulfonamido)-4-[3-(3-pyridyl)propyl]octanenitrile.
N#CCCC(CCCCNS(=O)(=O)c1ccc(Cl)cc1)CCCc1cccnc1
null
CCCCC(CCCc1cccnc1)CC(NS(=O)(=O)c1ccc(Cl)cc1)C(N)=O
c1ccncc1
O=C(OC(=O)C(F)(F)F)C(F)(F)F
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH:12]([CH2:16][CH:17]([CH2:22][CH2:23][CH2:24][C:25]2[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=2)CCCC)C(N)=O)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[N:31]1C=C[CH:34]=[CH:33][CH:32]=1.F[C:38](F)(F)[C:39](OC(=O)C(F)(F)F)=O>O1CCOCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH:11][CH2:12][CH2:16][CH2:17][CH2:22][CH:23]([CH2:24][CH2:25][CH2:30][C:29]2[CH:28]=[N:27][CH:26]=[CH:38][CH:39]=2)[CH2:34][CH2:33][C:32]#[N:31])(=[O:9])=[O:10])=[CH:6][CH:7]=1
3
C1COCCO1
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
1,043,228
CC(C)Oc1ccccc1O
O=C([O-])[O-]
[K+]
null
ord_dataset-3af92aec23dc4810b92eb0d8c60023ee
2011-01-01T00:03:00
true
2-[3-(2-Isopropoxy-phenoxy)-propyl]-isoindole-1,3-dione. To a solution of 2-isopropoxy-phenol (0.50 g, 3.3 mmol) in DMF (5 mL) was added K2CO3 (2.3 g, 17 mmol), and the resulting suspension was stirred at 25° C. for 15 min. A solution of 2-(3-bromo-propyl)-isoindole-1,3-dione (0.97 g, 3.6 mmol) in DMF (2 mL) was added, and the reaction mixture was heated to 80° C. for 18 h. The mixture was filtered, and the filtrate was diluted with 1:1 Et2O/EtOAc (100 mL), washed with H2O (2×20 mL) then brine (20 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography (5-20% EtOAc/hexanes) to provide the desired product (0.956 g, 87%). 1H NMR (400 MHz, CDCl3): 7.87-7.82 (m, 2H), 7.73-7.69 (m, 2H), 6.93-6.86 (m, 4H), 4.46 (hept, J=6.1 Hz, 1H), 4.06 (t, J=6.2 Hz, 2H), 3.92 (t, J=7.1 Hz, 2H), 2.20 (quint, J=6.4 Hz, 2H), 1.33 (d, J=6.1 Hz, 6H).
CC(C)Oc1ccccc1OCCCNCc1cccc(C(=O)N2CCCCC2)c1
null
CC(C)Oc1ccccc1OCCCN1C(=O)c2ccccc2C1=O
O=C1c2ccccc2C(=O)N1CCCBr
null
[CH:1]([O:4][C:5]1[CH:25]=[CH:24][CH:23]=[CH:22][C:6]=1[O:7][CH2:8][CH2:9][CH2:10][N:11]1[C:19](=O)[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)C1=O)([CH3:3])[CH3:2].C(OC1C=CC=CC=1O)(C)C.C([O-])([O-])=O.[K+].[K+].BrCCC[N:47]1[C:55](=[O:56])C2[C:49](=[CH:50][CH:51]=[CH:52]C=2)[C:48]1=O>CN(C=O)C>[CH:1]([O:4][C:5]1[CH:25]=[CH:24][CH:23]=[CH:22][C:6]=1[O:7][CH2:8][CH2:9][CH2:10][NH:11][CH2:19][C:18]1[CH:17]=[C:16]([C:55]([N:47]2[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]2)=[O:56])[CH:15]=[CH:14][CH:13]=1)([CH3:2])[CH3:3]
0.25
CN(C)C=O
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
919,209
O=[Pt]=O
null
null
null
ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d
2009-01-01T00:11:00
true
The title compound was prepared from {4-[4-(2-azido-propyl)-phenyl]-pyrimidin-2-yl}-(2,2,6,6-tetramethyl-piperidin-4-yl)-amine by hydrogenation using PtO2 in MeOH. Yield: 38 mg (81%).
CC(N)Cc1ccc(-c2ccnc(NC3CC(C)(C)NC(C)(C)C3)n2)cc1
null
CC(Cc1ccc(-c2ccnc(NC3CC(C)(C)NC(C)(C)C3)n2)cc1)N=[N+]=[N-]
null
null
[N:1]([CH:4]([CH3:29])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][CH:19]3[CH2:24][C:23]([CH3:26])([CH3:25])[NH:22][C:21]([CH3:28])([CH3:27])[CH2:20]3)[N:13]=2)=[CH:8][CH:7]=1)=[N+]=[N-]>CO.O=[Pt]=O>[NH2:1][CH:4]([CH3:29])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][CH:19]3[CH2:24][C:23]([CH3:26])([CH3:25])[NH:22][C:21]([CH3:28])([CH3:27])[CH2:20]3)[N:13]=2)=[CH:8][CH:7]=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
1,457,248
[Na+]
null
null
null
ord_dataset-a86112d52cd54525a5e36d41f18aced2
2014-01-01T00:07:00
true
Crude (R)-benzyl 2-(6-chloro-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3,3-dimethylbutanoate was dissolved in MeOH/THF (50%, 5 mL). Aqueous NaOH (1N, 2 mL) was added. The reaction mixture was stirred at 50° C. for 16 h and was purified via preparative mass trigger LC-MS (AcCN/H2O, 20-50%). The fractions were collected, concentrated, and dried in vacuo to afford the title compound as a yellow oil (34 mg, 38.9% from Step A starting material). 1H NMR (400 MHz, CD3OD) δ 1.22-1.32 (m, 9 H) 4.92 (br. s., 1 H) 5.18 (d, J=18.95 Hz, 1 H) 5.33 (d, J=18.95 Hz, 1 H) 7.88 (s, 1 H) 8.29 (s, 1 H). [M+H] calc'd for C15H16ClN3O3, 322; found, 322.5.
Cc1ccc(S(=O)(=O)n2cc(C(=O)O)c3c(CN[C@@H](C(=O)OCc4ccccc4)C(C)(C)C)c(Cl)cnc32)cc1
null
[OH-]
Cc1ccc(S(=O)(=O)n2cc3c4c(c(Cl)cnc42)CN([C@@H](C(=O)OCc2ccccc2)C(C)(C)C)C3=O)cc1
null
[Cl:1][C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([C:23]([CH3:26])([CH3:25])[CH3:24])[C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:14])[C:8](=[O:27])[C:7]3=[CH:28][N:29]([S:30]([C:33]4[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=4)(=[O:32])=[O:31])[C:5]([C:6]=23)=[N:4][CH:3]=1.[OH-:40].[Na+]>CO.C1COCC1>[CH2:16]([O:15][C:13](=[O:14])[C@H:12]([NH:9][CH2:10][C:11]1[C:2]([Cl:1])=[CH:3][N:4]=[C:5]2[N:29]([S:30]([C:33]3[CH:34]=[CH:35][C:36]([CH3:37])=[CH:38][CH:39]=3)(=[O:32])=[O:31])[CH:28]=[C:7]([C:8]([OH:40])=[O:27])[C:6]=12)[C:23]([CH3:26])([CH3:25])[CH3:24])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
16
C1CCOC1
CO
null
50
null
38.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,457,936
Cl
[Li+]
[O-2]
null
ord_dataset-a86112d52cd54525a5e36d41f18aced2
2014-01-01T00:07:00
true
To a solution of methyl 2-(2,6-dimethyl-4-p-tolylthieno[2,3-b]pyridin-5-yl)acetate (0.080 g; 0.246 mmol) in dioxane (4 mL) and water (1.5 mL) was added a 1N lithium oxide solution (1.5 mL; 1.50 mmol). The reaction mixture was heated at 60° C. for 4 h. After cooling to room temperature, the reaction mixture was acidified with 1N HCl (pH˜2) and partially concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was crystallized from a mixture of ethyl acetate/heptane to afford 0.037 g (48%) of the title compound as a beige solid.
Cc1ccc(-c2c(CC(=O)O)c(C)nc3sc(C)cc23)cc1
null
COC(=O)Cc1c(C)nc2sc(C)cc2c1-c1ccc(C)cc1
null
null
[CH3:1][C:2]1[S:23][C:5]2=[N:6][C:7]([CH3:22])=[C:8]([CH2:17][C:18]([O:20]C)=[O:19])[C:9]([C:10]3[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=3)=[C:4]2[CH:3]=1.[O-2].[Li+].[Li+].Cl>O1CCOCC1.O>[CH3:1][C:2]1[S:23][C:5]2=[N:6][C:7]([CH3:22])=[C:8]([CH2:17][C:18]([OH:20])=[O:19])[C:9]([C:10]3[CH:11]=[CH:12][C:13]([CH3:16])=[CH:14][CH:15]=3)=[C:4]2[CH:3]=1
null
C1COCCO1
O
null
60
null
48.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
503,422
Cl
null
null
null
ord_dataset-d673d02cdac14dba9ff59f12845a4f37
2001-01-01T00:05:00
true
To a solution of 0.7716 g (1.8 mM) of N-methyl-N-(1-tert-butoxycarbonylpiperidin-4-ylmethyl)-5-thia-1,8b-diazaacenaphthylene-4-carboxamide in ethanol (5 ml) was added 0.8 ml (9.6 mM) of 12N-hydrochloric acid at room temperature and the mixture was stirred for 18 hours. The solvent was then distilled off under reduced pressure, and 2 ml (24 mM) of 12N-hydrochloric acid was added to the residue. The mixture was stirred for 5 minutes, after which ethanol was added and the solvent was distilled off under reduced pressure. To the residue was further added ethanol and the ethanol, was distilled off under reduced pressure. The resulting crystals were collected by filtration and rinsed serially with ethanol, acetone, and diethyl ether to provide the title compound.
CN(CC1CCNCC1)C(=O)C1=Cc2cnc3cccc(n23)S1
null
CN(CC1CCN(C(=O)OC(C)(C)C)CC1)C(=O)C1=Cc2cnc3cccc(n23)S1
null
null
[CH3:1][N:2]([CH2:17][CH:18]1[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]1)[C:3]([C:5]1[S:15][C:14]2[N:16]3[C:7](=[CH:8][N:9]=[C:10]3[CH:11]=[CH:12][CH:13]=2)[CH:6]=1)=[O:4].[ClH:31]>C(O)C>[ClH:31].[ClH:31].[CH3:1][N:2]([CH2:17][CH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)[C:3]([C:5]1[S:15][C:14]2[N:16]3[C:7](=[CH:8][N:9]=[C:10]3[CH:11]=[CH:12][CH:13]=2)[CH:6]=1)=[O:4]
18
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
613,944
Cl
null
null
null
ord_dataset-5c4ee54447b84205a10f9c0473172972
2003-01-01T00:10:00
true
{3-[5-Methyl-3-(2-morpholinylsulfonylphenylsulfonyloxy)phenoxy]propoxy}guanidine hydrochloride: The title compound was prepared in 95% yield from 3-[5-methyl-[3-(2-morpholinylsulfonyl)phenylsulfonyloxy]phenoxy]propoxyamine, as prepared in the preceding step, in a manner analogous to step f of Example 1. 1H-NMR (300 MHz, DMSO-d6) δ 8.21 (t, J=8.0 Hz, 2H), 8.04 (t, J=7.8 Hz, 1H), 7.92 (t, J=7.8 Hz, 1H), 7.71 (br s, 4H), 6.75 (s, 1H), 6.53 (s, 1H), 6.49 (s, 1H), 3.99 (t, J=6.3 Hz, 2H), 3.90 (t, J=6.4 Hz, 2H), 3.62 (t, J=4.7 Hz, 4H), 3.25 (t, J=4.7 Hz, 4H), 2.22 (s, 3H), 2.02 (t, J=6.3 Hz, 2H). Mass spectrum (MALDI-TOF, α-cyano-4-hydroxycinnamic acid matrix) calcd. for C21H28N4O8S2: 529.1 (M+H), 551.1 (M+Na). Found: 528.9, 550.8.
CCOC(=O)C1CCN(S(=O)(=O)c2ccccc2S(=O)(=O)Oc2cc(C)cc(OCCCONC(=N)N)c2)CC1
null
Cc1cc(OCCCONC(=N)N)cc(OS(=O)(=O)c2ccccc2S(=O)(=O)N2CCOCC2)c1
N#CC(=Cc1ccc(O)cc1)C(=O)O
Cc1ccc(OS(=O)(=O)c2cccc(S(=O)(=O)C3CNCCO3)c2)c(OCCCON)c1
[ClH:1].[CH3:2][C:3]1[CH:4]=[C:5]([O:18][S:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[S:28]([N:31]2[CH2:36]COCC2)(=[O:30])=[O:29])(=[O:21])=[O:20])[CH:6]=[C:7]([CH:17]=1)[O:8][CH2:9][CH2:10][CH2:11][O:12][NH:13][C:14]([NH2:16])=[NH:15].[CH3:37][C:38]1C=CC(OS(C2C=CC=C(S(C3OCCNC3)(=O)=O)C=2)(=O)=O)=C(C=1)OCCCON.[C:69]([C:71](=[CH:75][C:76]1C=CC(O)=CC=1)[C:72]([OH:74])=[O:73])#N>>[ClH:1].[CH3:2][C:3]1[CH:4]=[C:5]([O:18][S:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[S:28]([N:31]2[CH2:76][CH2:75][CH:71]([C:72]([O:74][CH2:37][CH3:38])=[O:73])[CH2:69][CH2:36]2)(=[O:30])=[O:29])(=[O:21])=[O:20])[CH:6]=[C:7]([CH:17]=1)[O:8][CH2:9][CH2:10][CH2:11][O:12][NH:13][C:14]([NH2:16])=[NH:15]
null
null
null
null
null
95
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,548,126
CS(=O)(=O)Cl
[Na+]
null
null
ord_dataset-cac8df8aff894288876df4e093c9877f
2015-01-01T00:02:00
true
Under N2 atmosphere, 1-(4-(4-fluorophenoxy)pyrimidin-2-yl)ethanol (140 mg, 0.598 mmol) was dissolved in 3 mL anhydrous DCM. Triethylamine (0.175 mL, 1.26 mmol) was added, and the mixture was cooled to 0° C. MsCl (0.070 mL, 0.897 mmol) was added, and the mixture was stirred 15 minutes. Maintaining 0° C., DCM solvent was removed under N2 stream. Residue was taken up in 2 mL dry DMF. NaN3 (78 mg, 1.19 mmol) added, and the reaction was stirred at rt for 24 h. Mixture was poured into 20 mL water, and extracted with 20 mL EtOAc. Organic layer was washed with 20 mL brine and dried over Na2SO4. Filtered and concentrated to give 120 mg (77%) 2-(1-azidoethyl)-4-(4-fluorophenoxy)pyrimidine as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.49 (d, J=5.7 Hz, 1H), 7.16-6.90 (m, 4H), 6.70 (d, J=5.7 Hz, 1H), 4.34 (q, J=6.9 Hz, 1H), 1.55-1.46 (m, 3H).
CC(N=[N+]=[N-])c1nccc(Oc2ccc(F)cc2)n1
null
CC(O)c1nccc(Oc2ccc(F)cc2)n1
[N-]=[N+]=[N-]
null
[F:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([CH:13](O)[CH3:14])[N:8]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[N-:30]=[N+:31]=[N-:32].[Na+]>C(Cl)Cl.O>[N:30]([CH:13]([C:9]1[N:8]=[C:7]([O:6][C:5]2[CH:16]=[CH:17][C:2]([F:1])=[CH:3][CH:4]=2)[CH:12]=[CH:11][N:10]=1)[CH3:14])=[N+:31]=[N-:32]
0.25
ClCCl
CCN(CC)CC
O
0
null
77.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
605,602
CCCC[N+](CCCC)(CCCC)CCCC
[F-]
c1c[nH]cn1
null
ord_dataset-273fda773e864aaf9b71a30a2d9f2162
2003-01-01T00:08:00
true
To a solution of 4-[1-(trimethylsilyloxy)ethyl]-2-pyridinecarbonitrile (39.04 g, 0.1624 mol) in THF (200 ml) was added a solution of tetrabutylammonium fluoride in THF (1M, 178.6 ml, 0.1786 mol) at room temperature. After stirring for 0.5 h, the mixture was concentrated. The residue was diluted with ethyl acetate (300 ml) and washed with water (200 ml). The aqueous layer was then extracted with dichloromethane (200 ml×2). The combined organic layers were dried (MgSO4) and concentrated. The residual oil was dissolved in DMF (200 ml). To the solution was added tert-butyldimethylsilylchloride (36.72 g, 0.2436 mol) and imidazole (22.11 g, 0.3248 mol) at room temperture. After stirring for 19 h, diethyl ether (500 ml) and water (200 ml) were added to the mixture and the organic layer was separated. The organic layer was washed with water (100 ml×2), dried (MgSO4) and concentrated. The residue was purified by flash column chromatography eluting with ethyl acetate/hexane (1:20) to give 39.23 g (92%) of the title compound as an oil.
CC(O[Si](C)(C)C(C)(C)C)c1ccnc(C#N)c1
null
CC(O[Si](C)(C)C)c1ccnc(C#N)c1
CC(C)(C)[Si](C)(C)Cl
null
C[Si](C)(C)[O:3][CH:4]([C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]#[N:13])[CH:7]=1)[CH3:5].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si:34](Cl)([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35].N1C=CN=C1>C1COCC1.O.C(OCC)C>[Si:34]([O:3][CH:4]([C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]#[N:13])[CH:7]=1)[CH3:5])([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35]
0.5
O
C1CCOC1
CCOCC
null
null
92.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
377,146
O=C([O-])[O-]
[Cs+]
null
null
ord_dataset-846d411edee44814931e062174d7ef12
1997-01-01T00:09:00
true
4-Phenylphenol (1.70 g, 10 mmol) and cesium carbonate (3.91 g (12 mmol) were stirred at room temperature under a nitrogen atmosphere in 20 mL of dimethylformamide until it appeared that no more solid was dissolving. At that point, 1.42 mL (12 mmol) of bromoacetaldehyde dimethyl acetal (2.03 g, 12 mmol) were added to the mixture via syringe and the resulting brown suspension was stirred at room temperature overnight. The mixture was then heated under reflux for two hours and then stirred at room temperature overnight. At the end of this period, 100 mL of water and 200 mL of diethyl ether were added; the organics were extracted into the ether layer, which was separated, dried over anhydrous sodium sulfate and evaporated to yield 2.10 g (81% yield) of dimethoxy-2-(4-biphenyloxy)ethane.
COC(C)(OC)Oc1ccc(-c2ccccc2)cc1
null
Oc1ccc(-c2ccccc2)cc1
COC(CBr)OC
null
[C:1]1([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:20][O:21][CH:22]([O:25][CH3:26])[CH2:23]Br.O>CN(C)C=O.C(OCC)C>[CH3:20][O:21][C:22]([O:25][CH3:26])([O:13][C:10]1[CH:9]=[CH:8][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:12][CH:11]=1)[CH3:23]
8
CCOCC
O
CN(C)C=O
25
null
81.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
215,762
null
null
null
null
ord_dataset-5ebf3d05077a4f7fb91a1cd9bdc504d2
1990-01-01T00:09:00
true
6.9 g of 4-(2,3-dihydro-2,2-dimethyl-6-benzofuranylmethyloxy)aniline was dissolved into 70 ml of N,N-dimethylformamide, and 2.8 g of triethylamine was added thereto. 3.8 g of N-methoxy-N-methylcarbamoyl chloride was slowly added dropwise thereto. After the mixture was stirred at room temperature, the reaction mixture was poured into water and extracted with ethyl acetate. After the organic layer was washed with water, it was dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off and the residue was subjected to silica gel column chromatography using ethyl acetate/n-hexane (1/2) as a developer to obtain 6.0 g of Compound No. 4 shown in Table 1.
CON(C)C(=O)Nc1ccc(OCc2ccc3c(c2)OC(C)(C)C3)cc1
null
CON(C)C(=O)Cl
CC1(C)Cc2ccc(COc3ccc(N)cc3)cc2O1
null
[CH3:1][C:2]1([CH3:20])[CH2:6][C:5]2[CH:7]=[CH:8][C:9]([CH2:11][O:12][C:13]3[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=3)=[CH:10][C:4]=2[O:3]1.CN(C)C=O.C(N(CC)CC)C.[CH3:33][O:34][N:35]([CH3:39])[C:36](Cl)=[O:37]>O>[CH3:1][C:2]1([CH3:20])[CH2:6][C:5]2[CH:7]=[CH:8][C:9]([CH2:11][O:12][C:13]3[CH:19]=[CH:18][C:16]([NH:17][C:36]([N:35]([O:34][CH3:33])[CH3:39])=[O:37])=[CH:15][CH:14]=3)=[CH:10][C:4]=2[O:3]1
null
CN(C)C=O
CCN(CC)CC
O
25
65.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
667,490
CCCC[N+](CCCC)(CCCC)CCCC
[F-]
null
null
ord_dataset-c5ee194443334d3e92aff17e46e33bd1
2005-01-01T00:04:00
true
To a stirred solution of (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl-(1S,2R)-3-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-1-[4-(2-{[tert-butyl(dimethyl)silyl]oxy}ethoxy)benzyl]-2-hydroxypropylcarbamate (160 mg, 0.21 mmol) in tetrahydrofuran (3 mL) at 5° C. was added a mixture of tetrabutylammonium fluoride (0.3 mL, 1M in tetrahydrofuran) and glacial acetic acid (0.3 mL) over 2 minutes. The reaction was allowed to warm to ambient temperature and stirred for 18 hours. The mixture was diluted with ethyl acetate (50 mL), washed with water (25 mL) followed by saturated sodium bicarbonate (20 mL) and then brine (20 mL), dried (magnesium sulfate) and concentrated in vacuo to afford the title compound (135 mg, quant.) as a white solid. 1H NMR (DMSO-d6): δ 0.78 (6H, dd), 1.17-1.42 (2H, m), 1.92 (1H, m), 2.33 (1H, t), 2.64-2.78 (3H, m), 2.89-3.02 (2H, m), 3.24-3.29 (1H, m), 3.52-3.73 (7H, m), 3.78-3.82 (1H, m), 3.86 (2H, t), 4.78-4.82 (2H, m), 4.99 (1H, d), 5.46 (1H, d), 6.12 (2H, s), 6.73 (2H, d), 7.02-7.28 (6H, m); MS: 637 (MH+)
CC(C)CN(C[C@@H](O)[C@H](Cc1ccc(OCCO)cc1)NC(=O)O[C@H]1CO[C@H]2OCC[C@H]21)S(=O)(=O)c1ccc2c(c1)OCO2
null
CC(C)CN(C[C@@H](O)[C@H](Cc1ccc(OCCO[Si](C)(C)C(C)(C)C)cc1)NC(=O)O[C@H]1CO[C@H]2OCC[C@H]21)S(=O)(=O)c1ccc2c(c1)OCO2
null
null
[O:1]1[C@H:5]2[O:6][CH2:7][CH2:8][C@H:4]2[C@@H:3]([O:9][C:10](=[O:51])[NH:11][C@@H:12]([CH2:33][C:34]2[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH2:42][O:43][Si](C(C)(C)C)(C)C)=[CH:36][CH:35]=2)[C@H:13]([OH:32])[CH2:14][N:15]([S:20]([C:23]2[CH:31]=[CH:30][C:26]3[O:27][CH2:28][O:29][C:25]=3[CH:24]=2)(=[O:22])=[O:21])[CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:2]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(O)(=O)C>O1CCCC1.C(OCC)(=O)C>[O:27]1[C:26]2[CH:30]=[CH:31][C:23]([S:20]([N:15]([CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:14][C@@H:13]([OH:32])[C@@H:12]([NH:11][C:10](=[O:51])[O:9][C@@H:3]3[C@H:4]4[C@H:5]([O:6][CH2:7][CH2:8]4)[O:1][CH2:2]3)[CH2:33][C:34]3[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH2:42][OH:43])=[CH:36][CH:35]=3)(=[O:22])=[O:21])=[CH:24][C:25]=2[O:29][CH2:28]1
18
CCOC(C)=O
C1CCOC1
CC(=O)O
25
101
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
875,529
Cl
O=C([O-])[O-]
[K+]
null
ord_dataset-e1c3af9b105b4af09a5171403bbfc06f
2009-01-01T00:04:00
true
In a tube is combined (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine [200 mg, 0.6 mmol, Intermediate (44)], nipecotic acid (194 mg, 1.5 mmol), K2CO3 (249 mg, 1.8 mmol) and 1-methyl-2-pyrrolidinone (2.5 mL). The tube is sealed and heated to 140° C. and stirred for 5 hours. The mixture is allowed to cool to ambient temperature, stand for 12 hours, diluted with water (20 mL) and acidified using 3M HCl. A precipitate forms and is collected by filtration and dried under high vacuum to afford 1-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-piperidine-3-carboxylic acid [121 mg, 47%, Example 73] as a solid. LCMS RT=2.15 minutes, MS: 425 (M+H). IC50=0.8 nM
COc1nc(NCCc2ccc(Cl)cc2Cl)cc(N2CCCC(C(=O)O)C2)n1
null
O=C(O)C1CCCNC1
COc1nc(Cl)cc(NCCc2ccc(Cl)cc2Cl)n1
null
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[Cl:20])[CH:3]=1.[NH:21]1[CH2:29][CH2:28][CH2:27][CH:23]([C:24]([OH:26])=[O:25])[CH2:22]1.C([O-])([O-])=O.[K+].[K+].Cl>O.CN1CCCC1=O>[Cl:20][C:14]1[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=1[CH2:12][CH2:11][NH:10][C:4]1[N:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([N:21]2[CH2:29][CH2:28][CH2:27][CH:23]([C:24]([OH:26])=[O:25])[CH2:22]2)[CH:3]=1
5
CN1CCCC1=O
O
null
140
null
47.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,683,719
O=C([O-])[O-]
[K+]
null
null
ord_dataset-3953983e052a4076aa7cc0880b79cb8b
2016-01-01T00:01:00
true
A flask is charged with N-[5-(6-chloro-1H-indol-2-yl)-pyridin-3-ylmethyl]-methanesulfonamide (670 mg, 1.49 mmol), DMF (10 mL), dimethyl carbonate (403 mg, 4.47 mmol) and potassium carbonate (319 mg, 2.31 mmol), and the mixture is stirred at 150° C. for 5 h. The mixture is cooled to room temperature and purified using Xbridge C18 eluting with a 1:9 to 9:1 acetonitrile-water gradient to give N-[5-(6-chloro-1H-indol-2-yl)-pyridin-3-ylmethyl]-N-methyl-methanesulfonamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.74 (s, 3H), 3.02 (s, 3H), 4.35 (s, 2H), 7.04 (dd, J=8.5, 1.9 Hz, 1H), 7.09 (d, J=1.5 Hz, 1H), 7.43 (d, J=1.8 Hz, 1H), 7.59 (d, J=8.6 Hz, 1H), 8.14 (t, J=2.1 Hz, 1H), 8.47 (d, J=2.0 Hz, 1H), 9.05 (d, J=2.3 Hz, 1H), 11.92 (s, 1H). HRMS (ESI) m/z 350.0738 [(M+H)+ Calcd for C16H17ClN3O2S: 350.0730].
CN(Cc1cncc(-c2cc3ccc(Cl)cc3[nH]2)c1)S(C)(=O)=O
null
CS(=O)(=O)NCc1cncc(-c2cc3ccc(Cl)cc3[nH]2)c1
COC(=O)OC
null
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]3[CH:12]=[C:13]([CH2:17][NH:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH:14]=[N:15][CH:16]=3)[NH:8]2)=[CH:4][CH:3]=1.[C:23](=O)(OC)OC.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]3[CH:12]=[C:13]([CH2:17][N:18]([CH3:23])[S:19]([CH3:22])(=[O:20])=[O:21])[CH:14]=[N:15][CH:16]=3)[NH:8]2)=[CH:4][CH:3]=1
5
CN(C)C=O
null
null
150
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,186,866
[Pd]
null
null
null
ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff
2012-01-01T00:07:00
true
A suspension of 5-nitro-m-xylene (1.51 g) and 10% Pd/C (80 mg) in MeOH (50 mL) was stirred at room temperature under H2 balloon for 16 h. The reaction mixture was filtered through a Celite pad, washed with EtOAc, concentrated under reduced pressure. The crude product was purified by column chromatography (SiO2, EtOAc:Hexane=5:95 to 40:60) to give 3,5-dimethyl-phenylamine as a yellow oil: MS (m/z) 122 (M+1); 1H NMR (CDCl3, 400 MHz) δ 6.41 (s, 1H), 6.33 (s, 2H), 3.52 (s, 2H), 2.22 (s, 6H).
Cc1cc(C)cc(N)c1
null
Cc1cc(C)cc([N+](=O)[O-])c1
null
null
[N+:1]([C:4]1[CH:5]=[C:6]([CH3:11])[CH:7]=[C:8]([CH3:10])[CH:9]=1)([O-])=O>CO.[Pd]>[CH3:10][C:8]1[CH:9]=[C:4]([NH2:1])[CH:5]=[C:6]([CH3:11])[CH:7]=1
16
CO
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
1,629,552
O=C([O-])[O-]
[K+]
null
null
ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d
2015-01-01T00:09:00
true
A mixture of 4-chloro-1-[4-hydroxy-2-((S)-3-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carbonyl)-phenyl]-5-methyl-1H-pyrazole-3-carboxylic acid dibutylamide (intermediate D, 170 mg, 0.31 mmol), ethyl 2-iodoacetate (99 mg, 0.46 mmol), potassium carbonate (13 mg, 0.092 mmol), and triethylamime (0.085 mL, 0.62 mmol) was stirred in acetonitrile (3 mL) at ambient temperature for 12 hours. The solvent was removed in vacuo. The crude material was purified by eluting through a silica gel column with a 10 to 100% ethyl acetate/heptane gradient to afford the title compound (15 mg, 7.6% yield). MS (ESI) [m/e, (M+H)+]=639.3. 1H NMR (400 MHz, chloroform-d) δ ppm 6.73-7.39 (m, 7H), 2.51-5.41 (m, 17H), 2.16-2.41 (m, 3H), 0.68-1.70 (m, 16H).
CCCCN(CCCC)C(=O)c1nn(-c2ccc(OCC(=O)OCC)cc2C(=O)N2Cc3ccccc3C[C@H]2CO)c(C)c1Cl
null
CCCCN(CCCC)C(=O)c1nn(-c2ccc(O)cc2C(=O)N2Cc3ccccc3C[C@H]2CO)c(C)c1Cl
CCOC(=O)CI
null
[CH2:1]([N:5]([CH2:36][CH2:37][CH2:38][CH3:39])[C:6]([C:8]1[C:12]([Cl:13])=[C:11]([CH3:14])[N:10]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:16]=2[C:22]([N:24]2[C@H:33]([CH2:34][OH:35])[CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH2:25]2)=[O:23])[N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4].I[CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:45]([O:44][C:42](=[O:43])[CH2:41][O:21][C:18]1[CH:19]=[CH:20][C:15]([N:10]2[C:11]([CH3:14])=[C:12]([Cl:13])[C:8]([C:6](=[O:7])[N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:36][CH2:37][CH2:38][CH3:39])=[N:9]2)=[C:16]([C:22]([N:24]2[C@H:33]([CH2:34][OH:35])[CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH2:25]2)=[O:23])[CH:17]=1)[CH3:46]
null
CC#N
null
null
null
null
7.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
522,000
COc1ccc([C@@H](Sc2ccccc2[N+](=O)[O-])[C@H](O)C(=O)O)cc1
null
null
null
ord_dataset-262b40ea420c471da9b9244fe9b8f645
2001-01-01T00:10:00
true
By treating (±)-4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidine and (2R,3R)-2-hydroxy-3-(4-methoxy-phenyl)-3-(2-nitrophenylthio)propionic acid in the same manner as in Example 4-(1), (2) and (3) to afford (S)-4-[(4-chlorophenyl) (2-pyridyl)methoxy]piperidine.
Clc1ccc([C@H](OC2CCNCC2)c2ccccn2)cc1
null
Clc1ccc(C(OC2CCNCC2)c2ccccn2)cc1
null
null
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[O:9][CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.O[C@@H]([C@@H](C1C=CC(OC)=CC=1)SC1C=CC=CC=1[N+]([O-])=O)C(O)=O>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[O:9][CH:10]2[CH2:11][CH2:12][NH:13][CH2:14][CH2:15]2)=[CH:4][CH:3]=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
1,593,105
null
null
null
null
ord_dataset-e8c6a25568b64529b960953990e6921f
2015-01-01T00:06:00
true
3-((5-chloro-1-(4-fluorobutyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)methyl)-1-cyclopropyl-1H-imidazo[4,5-c]pyridin-2(3H)-one P11 was synthesized following the procedure reported for the synthesis of 3-((3-bromo-1-(3-(methylsulfonyl)propyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)methyl)-1-cyclopropyl-1H-imidazo[4,5-c]pyridin-2(3H)-one P17, using (5-chloro-1-(4-fluorobutyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)methanol 10 instead of (3-bromo-1-(3-(methylsulfonyl)propyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)methanol 12. 1H NMR (360 MHz, DMSO-d6) δ ppm 0.87-0.97 (m, 2H), 1.02-1.13 (m, 2H), 1.57-1.78 (m, 4H), 2.99 (tt, J=6.9, 3.6 Hz, 1H), 4.30-4.43 (m, 3H), 4.49 (m, J=5.7, 5.7 Hz, 1H), 5.35 (s, 2H), 6.53 (s, 1H), 7.29 (d, J=5.5 Hz, 1H), 7.56 (s, 1H), 8.26 (d, J=5.1 Hz, 1H), 8.37 (s, 1H), 8.70 (s, 1H); m/z=414 (M+H)+.
O=c1n(Cc2cc3cc(Cl)ncc3n2CCCCF)c2cnccc2n1C1CC1
null
CS(=O)(=O)CCCn1c(Cn2c(=O)n(C3CC3)c3ccncc32)c(Br)c2cnccc21
OCc1cc2cc(Cl)ncc2n1CCCCF
null
BrC1C2C=NC=CC=2N(CCCS(C)(=O)=O)C=1C[N:19]1[C:23]2[CH:24]=[N:25][CH:26]=[CH:27][C:22]=2[N:21]([CH:28]2[CH2:30][CH2:29]2)[C:20]1=[O:31].[Cl:32][C:33]1[CH:34]=[C:35]2[CH:41]=[C:40]([CH2:42]O)[N:39]([CH2:44][CH2:45][CH2:46][CH2:47][F:48])[C:36]2=[CH:37][N:38]=1>>[Cl:32][C:33]1[CH:34]=[C:35]2[CH:41]=[C:40]([CH2:42][N:19]3[C:23]4[CH:24]=[N:25][CH:26]=[CH:27][C:22]=4[N:21]([CH:28]4[CH2:29][CH2:30]4)[C:20]3=[O:31])[N:39]([CH2:44][CH2:45][CH2:46][CH2:47][F:48])[C:36]2=[CH:37][N:38]=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
1,391,160
[F-]
[K+]
null
null
ord_dataset-31641fb65b34430fa7435229b949b604
2014-01-01T00:01:00
true
To a suspension of 2-(4-(8-bromo-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile (Intermediate 1, 0.050 g, 0.12 mmol) and potassium fluoride (0.010 g, 0.18 mmol) in dry benzene (6 ml) was added 1-bromo-2-isocyanatobenzene (0.036 g, 0.12 mmol) at RT. The reaction was stirred at reflux temperature for 6 hours. The reaction mixture was cooled and poured into cold water, extracted with ethyl acetate (2×20 ml). Organic layer was washed with water dried over sodium sulfate and concentrated. The crude product was crystallized in ethyl acetate\pet ether to obtain the title compound. Yield: 0.017 g (22%); 1H NMR (DMSO-d6, 300 MHz): δ 11.82 (s, 1H), 8.78 (s, 1H), 7.90 (d, 1H, J=9 Hz), 7.81 (d, 2H, J=8.1 Hz), 7.61-7.65 (m, 3H), 7.28 (d, 1H, J=8.1 Hz), 6.95-7.05 (m, 2H), 6.74 (d, 1H, 7.8 Hz), 6.41 (t, 1H, 7.2 Hz), 1.79 (s, 6H); MS: m/z 606 (M+).
CC(C)(C#N)c1ccc(-n2c(=O)n(C(=O)Nc3ccccc3Br)c3cnc4ccc(Br)cc4c32)cc1
null
O=C=Nc1ccccc1Br
CC(C)(C#N)c1ccc(-n2c(=O)[nH]c3cnc4ccc(Br)cc4c32)cc1
null
[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[NH:12][C:13](=[O:26])[N:14]([C:15]4[CH:20]=[CH:19][C:18]([C:21]([CH3:25])([CH3:24])[C:22]#[N:23])=[CH:17][CH:16]=4)[C:5]=3[C:4]=2[CH:3]=1.[F-].[K+].[Br:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[N:36]=[C:37]=[O:38].O>C1C=CC=CC=1>[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([C:37]([NH:36][C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=4[Br:29])=[O:38])[C:13](=[O:26])[N:14]([C:15]4[CH:20]=[CH:19][C:18]([C:21]([C:22]#[N:23])([CH3:24])[CH3:25])=[CH:17][CH:16]=4)[C:5]=3[C:4]=2[CH:3]=1
null
c1ccccc1
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
462,247
O=C([O-])[O-]
[K+]
null
null
ord_dataset-5ca9db262dd24c5a9315cdc8ef055b7e
2000-01-01T00:04:00
true
A mixture of 2-fluoro-4-hydroxybenzonitrile (S. M. Kelly, Helv.Chim.Acta. 1984, Volume 67, P.1572-1579) (30 g), potassium carbonate (45.36 g) and 3,4-methylenedioxybenzyl chloride (42.65 g) in dimethylformamide (500 ml) was stirred at 90° C. for 2 hours. The reaction mixture was filtered and the filtrate evaporated. The residue was stirred with ethyl acetate (500 ml) and filtered affording the title compound (32.1 g) as a cream coloured solid, m.p. 139-140° C.
N#Cc1ccc(OCc2ccc3c(c2)OCO3)cc1F
null
N#Cc1ccc(O)cc1F
ClCc1ccc2c(c1)OCO2
null
[F:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C(=O)([O-])[O-].[K+].[K+].[CH2:17]1[O:27][C:26]2[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][C:19]=2[O:18]1>CN(C)C=O>[O:27]1[C:26]2[CH:25]=[CH:24][C:21]([CH2:22][O:10][C:8]3[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=3)=[CH:20][C:19]=2[O:18][CH2:17]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
147,965
NCCNc1cccc2[nH]ncc12
c1ccc(COc2ccc(OCC3CO3)cc2)cc1
null
null
ord_dataset-2069a3db775a4d9f9310aca092ecbad8
1986-01-01T00:08:00
true
The 1-(4-benzyloxyphenoxy)-3-[2-(indazol-4-ylamino)-ethylamino]-propan-2-ol used as starting material can be obtained in the following manner: 5.1 g. 4-benzyloxyphenyl glycidyl ether and 7.0 g. 4-(2-aminoethylamino)-indazole are dissolved in 10 ml. dimethylformamide and left to stand for 2 days at ambient temperature. The reaction mixture is then digested by the addition of 20 ml. methanol, filtered off with suction and then washed with methanol. There are obtained 5.0 g. (58% of theory) of the desired product in the form of colorless crystals; m.p. 151°-153° C.
Oc1ccc(OCC(O)CNCCNc2cccc3[nH]ncc23)cc1
null
OC(CNCCNc1cccc2[nH]ncc12)COc1ccc(OCc2ccccc2)cc1
null
null
C([O:8][C:9]1[CH:32]=[CH:31][C:12]([O:13][CH2:14][CH:15]([OH:30])[CH2:16][NH:17][CH2:18][CH2:19][NH:20][C:21]2[CH:29]=[CH:28][CH:27]=[C:26]3[C:22]=2[CH:23]=[N:24][NH:25]3)=[CH:11][CH:10]=1)C1C=CC=CC=1.C(OC1C=CC(OCC2C=CC=CC=2)=CC=1)C1OC1.NCCNC1C=CC=C2C=1C=NN2>CN(C)C=O>[OH:8][C:9]1[CH:10]=[CH:11][C:12]([O:13][CH2:14][CH:15]([OH:30])[CH2:16][NH:17][CH2:18][CH2:19][NH:20][C:21]2[CH:29]=[CH:28][CH:27]=[C:26]3[C:22]=2[CH:23]=[N:24][NH:25]3)=[CH:31][CH:32]=1
48
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
1,681,114
CC[O-]
O=C([O-])O
[Na+]
null
ord_dataset-3953983e052a4076aa7cc0880b79cb8b
2016-01-01T00:01:00
true
A solution of 6-bromoquinoline-5-carbonitrile (16b) (300 mg, 1.29 mmol), ethyl mercaptoacetate (212 μL, 1.93 mmol) and sodium ethoxide (122.6 mg, 1.80 mmol) in dimethylformamide (10 mL) was stirred at room temperature for 15 hours. A saturated aqueous solution of sodium bicarbonate was added to the mixture. It was extracted twice with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The intermediate ethyl 2-[(5-cyanoquinolin-6-yl)sulfanyl]acetate obtained was reacted with sodium ethoxide (122.6 mg, 1.80 mmol) in dimethylformamide (8 mL) by stirring at 90° C. for 3 hours. The reaction was cooled to room temperature and water was added (10 mL). The resulting precipitate was filtered and washed with water twice and dried under vacuum with phosphorus pentoxide to afford the desired product (16c) as a solid (299 mg, 1.10 mmol, 85%).
CCOC(=O)CSc1ccc2ncccc2c1C#N
null
CCOC(=O)CS
N#Cc1c(Br)ccc2ncccc12
null
Br[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][CH:6]=[CH:5][C:4]=2[C:3]=1[C:12]#[N:13].[SH:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17].[O-]CC.[Na+].C(=O)(O)[O-].[Na+]>CN(C)C=O>[C:12]([C:3]1[C:2]([S:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[N:8]2)#[N:13]
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
228,937
null
null
null
null
ord_dataset-9adbd9cd2fd941f7af27fb31c9bf3bac
1991-01-01T00:06:00
true
A solution of 0.5 g of (S,S)-2,4-dibenzylglutaric anhydride and 0.82 g of O-benzyl-(L)-serine 1,2:5,6-di-O-isopropylidene-D-glucofuranos-3-yl ester in 10 ml of methylene chloride is stirred at room temperature overnight. The solution is diluted with ether, washed with 1N hydrochloric acid, water, dried (Na2S04), filtered and concentrated to give N-[(S,S)-2,4-dibenzyl-4-carboxybutyryl]-O-benzyl-(L)-serine 1,2:5,6-di-O-isopropylidene-D-glucofuranos-3-yl ester melting at 55°-58°; [α]D =+2.2°.
O=C(O)[C@H](Cc1ccccc1)C[C@@H](Cc1ccccc1)C(=O)N[C@@H](COCc1ccccc1)C(=O)O
null
N[C@@H](COCc1ccccc1)C(=O)O
O=C1OC(=O)[C@H](Cc2ccccc2)C[C@H]1Cc1ccccc1
null
[CH2:1]([C@@H:8]1[CH2:14][C@@H:13]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:12](=[O:22])[O:11][C:9]1=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:23]([O:30][CH2:31][C@@H:32]([C:34]([OH:36])=[O:35])[NH2:33])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(Cl)Cl.CCOCC>[CH2:15]([C@H:13]([CH2:14][C@@H:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:9]([OH:11])=[O:10])[C:12]([NH:33][C@H:32]([C:34]([OH:36])=[O:35])[CH2:31][O:30][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:22])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
null
CCOCC
ClCCl
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
1,741,605
BrB(Br)Br
N
null
null
ord_dataset-eacfee6d16d8455a93348409f1b37be4
2016-01-01T00:06:00
true
5-bromo-1-cyclopropyl-7-methoxy-1H-benzo[d]imidazole (0.54 g, 2.01 mmol) was dissolved in dichloromethane (12 mL) under N2. A 1M BBr3 solution in DCM (12 mL, 12 mmol) was added dropwise over 1 min. The resulting stirred suspension was heated to 35° C. After 5 h, the reaction mixture was cooled in an ice water bath. A 7M ammonia in MeOH solution (7.5 mL, 53 mmol) was then added over 2 min via syringe. The mixture was stirred 5 min and was removed from the ice bath. After an additional 10 min, the mixture was concentrated in vacuo, and the crude product was dissolved in MeOH (30 mL) and was concentrated in vacuo. The resulting crude solids were suspended in 20% MeOH in DCM (30 mL) and were filter through a short pad of silica, eluting with 20% MeOH in DCM. Filtrate was concentrated in vacuo, and the crude product was adsorbed onto silica gel. Purification by silica gel chromatography (0-20% MeOH in DCM) gave 5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-ol (2.73). LCMS-ES r (m/z): [m+H]+ calcd for C10H10BrN2O: 253.00; found: 253.14.
Oc1cc(Br)cc2ncn(C3CC3)c12
null
COc1cc(Br)cc2ncn(C3CC3)c12
null
null
[Br:1][C:2]1[CH:13]=[C:12]([O:14]C)[C:5]2[N:6]([CH:9]3[CH2:11][CH2:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1.B(Br)(Br)Br.N.CO>ClCCl>[Br:1][C:2]1[CH:13]=[C:12]([OH:14])[C:5]2[N:6]([CH:9]3[CH2:11][CH2:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1
5
CO
ClCCl
null
35
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,342,345
O=S(=O)(O)O
null
null
null
ord_dataset-08852243bba44cb28769a5833f1515fe
2013-01-01T00:09:00
true
4-Hydroxy-3-iodobenzonitrile was prepared by the method analogous to Preparation 341 above using N-iodosuccinimide, acetic acid, sulfuric acid and 4-Hydroxybenzonitrile. Purified by ISCO™ (80 g SiO2) eluting with ethyl acetate:heptane (gradient 0:1 to 3:7, by volume) to yield the title compound.
N#Cc1ccc(O)c(I)c1
null
O=C1CCC(=O)N1I
N#Cc1ccc(O)cc1
null
[I:1]N1C(=O)CCC1=O.S(=O)(=O)(O)O.[OH:14][C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][CH:16]=1>C(O)(=O)C>[OH:14][C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][C:16]=1[I:1]
null
CC(=O)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
1,241,437
CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC
On1nnc2ccccc21
null
null
ord_dataset-c544c0c663f54dbea4ddb52ddde7934e
2013-01-01T00:01:00
true
3-[(4-Methoxybenzyl)oxy]benzoic acid (9.26 g, 35.9 mmol), acethydrazide (3.98 g, 53.8 mmol), HOBT (6.59 g, 43 mmol) and EDC (10.3 g, 53.8 mmol) were weighed into a 200 mL RB flask. DMF (60 mL) was added. The mixture was stirred vigorously at room temperature. The solid dissolved within 5 min. LC-MS showed complete consumption of the acid after 30 min. DMF was removed at 60° C. under vacuum. The residue was treated with 100 mL EtOAc/water (1/1) and was allowed to stand overnight. The solid was collected via filtration and washed with EtOAc. The crude N′-acetyl-3-[(4-methoxybenzyl)oxy]benzohydrazide (8 g) was suspended in 100 mL THF and was heated under reflux in the presence of Burgess' reagent (12.8 g, 53.8 mmol) for 1 hour. The solution was cooled and directly passed through a plug of silica gel (300 gram) which was washed thoroughly with 20% acetone/hexanes. The eluent was concentrated to give the crude product as white solid.
COc1ccc(COc2cccc(-c3nnc(C)o3)c2)cc1
null
CC(=O)NN
COc1ccc(COc2cccc(C(=O)O)c2)cc1
null
[CH3:1][O:2][C:3]1[CH:19]=[CH:18][C:6]([CH2:7][O:8][C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=2)[C:12]([OH:14])=O)=[CH:5][CH:4]=1.[C:20]([NH:23][NH2:24])(=O)[CH3:21].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][O:8][C:9]2[CH:10]=[C:11]([C:12]3[O:14][C:20]([CH3:21])=[N:23][N:24]=3)[CH:15]=[CH:16][CH:17]=2)=[CH:18][CH:19]=1
8
ClCCCl
CN(C)C=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
1,292,207
null
null
null
null
ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c
2013-01-01T00:05:00
true
This compound was prepared by using procedures analogous to those described for the synthesis of Example 30 starting from 4-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine and 1-acetylpiperazine (Aldrich Cat. No. 359513). LCMS (M+H)+: m/z=451.2.
CC(=O)N1CCN(c2ccc3c(c2)CN(c2cc(N4CCN(C)CC4)nc(N)n2)CC3)CC1
null
CC(=O)N1CCNCC1
CN1CCN(c2cc(N3CCc4ccc(Br)cc4C3)nc(N)n2)CC1
null
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:12]3[CH:17]=[C:16]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[N:15]=[C:14]([NH2:25])[N:13]=3)[CH2:9]2)=[CH:4][CH:3]=1.[C:26]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)(=[O:28])[CH3:27]>>[C:26]([N:29]1[CH2:34][CH2:33][N:32]([C:2]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][N:8]([C:12]4[CH:17]=[C:16]([N:18]5[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]5)[N:15]=[C:14]([NH2:25])[N:13]=4)[CH2:9]3)=[CH:4][CH:3]=2)[CH2:31][CH2:30]1)(=[O:28])[CH3:27]
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
620,662
Cl
null
null
null
ord_dataset-c9f990dde2dc45d0948ecbe037a0d819
2004-01-01T00:01:00
true
In analogy to the procedure described in example 20b, 4-chloro-2,6-bis-(2-hydroxy-ethylamino)-pyrimidine-5-carbonitrile was treated with 4-phenyl-1,2,3,6-tetrahydro-pyridine hydrochloride in ethanol in the presence of N-ethyl-diisopropylamine at 80° C. to yield 2,4-bis-(2-hydroxy-ethylamino)-6-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)-pyrimidine-5-carbonitrile as an amorphous, brown solid; MS: [M+H]+=381.
N#Cc1c(NCCO)nc(NCCO)nc1N1CC=C(c2ccccc2)CC1
null
N#Cc1c(Cl)nc(NCCO)nc1NCCO
C1=C(c2ccccc2)CCNC1
null
Cl[C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][CH2:11][CH2:12][OH:13])[N:5]=[C:4]([NH:14][CH2:15][CH2:16][OH:17])[N:3]=1.Cl.[C:19]1([C:25]2[CH2:26][CH2:27][NH:28][CH2:29][CH:30]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(N(C(C)C)C(C)C)C>C(O)C>[OH:17][CH2:16][CH2:15][NH:14][C:4]1[N:5]=[C:6]([NH:10][CH2:11][CH2:12][OH:13])[C:7]([C:8]#[N:9])=[C:2]([N:28]2[CH2:27][CH:26]=[C:25]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:30][CH2:29]2)[N:3]=1
null
CCO
CCN(C(C)C)C(C)C
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
604,216
[Na+]
[OH-]
null
null
ord_dataset-273fda773e864aaf9b71a30a2d9f2162
2003-01-01T00:08:00
true
Using General Procedure I; a solution of ethyl 4-{4-[1-(benzylmethylamino)-cyclopropyl]-phenylethynyl}-benzoate (Compound 115, 65.0 mg, 0.16 mmol) in ethanol (3 mL) and tetrahydrofuran (3 mL) was treated with NaOH (80.0 mg, 2.0 mmols, 2.0 mL of a 1N aqueous solution) and stirred overnight at room temperature. Work-up afforded 45.0 mg (75%) of the title compound as a solid.
O=C(O)c1ccc(C#Cc2ccc(C3(NCCc4ccccc4)CC3)cc2)cc1
null
CCOC(=O)c1ccc(C#Cc2ccc(C3(NCCc4ccccc4)CC3)cc2)cc1
null
null
[CH2:1]([CH2:8][NH:9][C:10]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][C:21]3[CH:31]=[CH:30][C:24]([C:25]([O:27]CC)=[O:26])=[CH:23][CH:22]=3)=[CH:15][CH:14]=2)[CH2:12][CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>C(O)C.O1CCCC1>[CH2:1]([CH2:8][NH:9][C:10]1([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][C:21]3[CH:31]=[CH:30][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=3)=[CH:15][CH:14]=2)[CH2:11][CH2:12]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
8
C1CCOC1
CCO
null
25
null
73.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
377,789
null
null
null
null
ord_dataset-846d411edee44814931e062174d7ef12
1997-01-01T00:09:00
true
A 100 mL one-neck round-bottom flask equipped for magnetic stirring was charged with 2-bromo-2-(4-methylthiophenyl)-1(4-methylphenyl)ethanone from Step 3 (0.300 g, 0.895 mmol) and acetonitrile (20 mL). 2-Chlorothiobenzamide (0.154 g, 0.895 mmol) was added, and the suspension was heated and held at reflux for three hours. The reaction was cooled to room temperature, diluted with ethyl acetate (50 mL) and poured into water(50 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (2×30 mL). The combined organic solution was dried over MgSO4, filtered and evaporated in vacuo. The residue was purified via flash chromatography (silica gel; 5% ethyl acetate in hexane) to yield 2-(2-chlorophenyl)-4-(4-methylphenyl)-5-(4-methylthiophenyl)thiazole (0.284 g, 78%) as a white solid: mp 125°-126° C. 1H NMR (CDCl3) 300 MHz 8.40(m, 1H), 7.62-7.11(m, 11H), 2.50 (s, 3H), 3.36(s, 3H). Mass spectrum: MH+ =407.
CSc1ccc(-c2sc(-c3ccccc3Cl)nc2-c2ccc(C)cc2)cc1
null
NC(=S)c1ccccc1Cl
CSc1ccc(C(Br)C(=O)c2ccc(C)cc2)cc1
null
Br[CH:2]([C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=1)=O.C(#N)C.[Cl:23][C:24]1[CH:32]=[CH:31][CH:30]=[CH:29][C:25]=1[C:26]([NH2:28])=[S:27].O>C(OCC)(=O)C>[Cl:23][C:24]1[CH:32]=[CH:31][CH:30]=[CH:29][C:25]=1[C:26]1[S:27][C:2]([C:12]2[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=2)=[C:3]([C:5]2[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=2)[N:28]=1
null
CCOC(C)=O
CC#N
O
25
null
77.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,362,030
[Na+]
[OH-]
null
null
ord_dataset-d932d1d683704a8bad3d064bcb197acc
2013-01-01T00:11:00
true
To a solution of 2-ethyl-4-[5-(2-ethyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenol (89 mg, 0.276 mmol) in 3 N aq. NaOH (1 mL) and isopropanol (4 mL), (R)-epichlorohydrine (142 mg, 1.53 mmol) is added. The mixture is stirred at rt for 24 h before another portion of (R)-epichlorohydrine (142 mg; 1.53 mmol) is added. Stirring is continued for another 24 h at rt. The mixture is diluted with EA (50 mL) and washed with 1M aq. NaOH (10 mL) and brine (10 mL). The org. phase is dried over MgSO4, filtered and evaporated to give crude (S)-2-ethyl-4-[3-(3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-6-methyl-pyridine; LC-MS*: tR=1.11* min; [M+1]+=380.24.
CCc1cc(-c2nc(-c3cc(C)c(OC[C@@H]4CO4)c(CC)c3)no2)cc(C)n1
null
CCc1cc(-c2nc(-c3cc(C)c(O)c(CC)c3)no2)cc(C)n1
ClC[C@H]1CO1
null
[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[N:17]=[C:16]([CH2:21][CH3:22])[CH:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:23])[C:4]=1[OH:24])[CH3:2].[CH2:25]([C@@H:27]1[O:29][CH2:28]1)Cl>[OH-].[Na+].C(O)(C)C.CC(=O)OCC>[CH2:21]([C:16]1[CH:15]=[C:14]([C:12]2[O:11][N:10]=[C:9]([C:7]3[CH:6]=[C:5]([CH3:23])[C:4]([O:24][CH2:25][C@@H:27]4[CH2:28][O:29]4)=[C:3]([CH2:1][CH3:2])[CH:8]=3)[N:13]=2)[CH:19]=[C:18]([CH3:20])[N:17]=1)[CH3:22]
24
CCOC(C)=O
CC(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
55,198
null
null
null
null
ord_dataset-159c363342e44b539e7a5975c873e30d
1979-01-01T00:05:00
true
This titled benzamide was prepared according to the general acid chloride method described above on a 0.01 mol scale by reacting the trans-2-[N-(2-furylmethyl)methylamino]cyclohexylamine, prepared as described in part (a) above with 3,4-dichlorobenzoyl chloride. The reaction product mixture was extracted with methylene dichloride to extract the benzamide product therefrom. The crude product was chromatographed on 380 g. of silica gel using a 1 percent methanol-in-chloroform eluant. Fraction 1 (1000 m.) and fractions 2 to 17 (25 ml. each) gave no material. Fractions 18 to 54 (25 ml. each) gave a solid which was crystallized from ether giving colorless needles, 1.91 g., (50% yield) of the named benzamide product, melting point 149°-150° C. The Ultraviolet, Infrared, and Nuclear Magnetic Resonance spectral analyses were consistent for the named benzamide.
CN(Cc1ccco1)[C@@H]1CCCC[C@H]1NC(=O)c1ccc(Cl)c(Cl)c1
null
CN(Cc1ccco1)[C@@H]1CCCC[C@H]1N
O=C(Cl)c1ccc(Cl)c(Cl)c1
null
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]([CH3:15])[C@@H:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[NH2:14].[Cl:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=1[Cl:26])[C:20](Cl)=[O:21]>>[Cl:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=1[Cl:26])[C:20]([NH:14][C@@H:9]1[CH2:10][CH2:11][CH2:12][CH2:13][C@H:8]1[N:7]([CH2:6][C:2]1[O:1][CH:5]=[CH:4][CH:3]=1)[CH3:15])=[O:21]
null
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
602,441
Cc1ccc(S(=O)(=O)O)cc1
O=C([O-])O
[Na+]
null
ord_dataset-82e842e611ef4a05b6e7f9ea0a46d52d
2003-01-01T00:07:00
true
100 μl of hydrazine hydrate and 3 mg of paratoluenesulphonic acid are added to 300 mg of the product obtained in Example 73 in 3 cm3 of methanol. Agitation is carried out for 16 hours at ambient temperature, 50 cm3 of an aqueous solution of sodium bicarbonate is added, extraction is carried out with methylene chloride, the solvent is evaporated off, the residue is chromatographed on silica (eluant: ethyl acetate) and 190 mg of expected product is obtained.
C[C@]12C[C@H](c3ccc(OCCCCCS(=O)(=O)CCCC(F)(F)C(F)(F)F)cc3)[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1CCC2=NN
null
NN
C[C@]12C[C@H](c3ccc(OCCCCCS(=O)(=O)CCCC(F)(F)C(F)(F)F)cc3)[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1CCC2=O
null
O.[NH2:2][NH2:3].C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH:15][C:16]1[CH:33]=[CH:32][C:31]2[C@@H:30]3[C@H:21]([C@H:22]4[C@@:26]([CH2:28][C@@H:29]3[C:34]3[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][S:46]([CH2:49][CH2:50][CH2:51][C:52]([F:58])([F:57])[C:53]([F:56])([F:55])[F:54])(=[O:48])=[O:47])=[CH:36][CH:35]=3)([CH3:27])[C:25](=O)[CH2:24][CH2:23]4)[CH2:20][CH2:19][C:18]=2[CH:17]=1.C(=O)(O)[O-].[Na+]>CO>[OH:15][C:16]1[CH:33]=[CH:32][C:31]2[C@@H:30]3[C@H:21]([C@H:22]4[C@@:26]([CH2:28][C@@H:29]3[C:34]3[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][S:46]([CH2:49][CH2:50][CH2:51][C:52]([F:58])([F:57])[C:53]([F:56])([F:55])[F:54])(=[O:48])=[O:47])=[CH:36][CH:35]=3)([CH3:27])[C:25](=[N:2][NH2:3])[CH2:24][CH2:23]4)[CH2:20][CH2:19][C:18]=2[CH:17]=1
16
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
1,474,632
null
null
null
null
ord_dataset-c3c1091f873b4f40827973a6f1f9b685
2014-01-01T00:09:00
true
The mixture of 5-[3-Amino-2-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-1-methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-1H-pyridin-2-one (0.2 g, 0.36 mmol), 4-bromo-2-(2-bromo-ethyl)-benzenesulfonyl chloride (0.4 g, 1.08 mmol) and DIPEA (1 mL) in dichloroethane (10 mL) was microwaved at 120° C. for 30 min, then added 4-bromo-2-(2-bromo-ethyl)-benzenesulfonyl chloride (0.4 g, 1.08 mmol) and DIPEA (1 mL) and microwaved at 120° C. for 30 min. After repeating this process three times, the mixture was concentrated to afford a dark residue. Purification by silica gel chromatography (methylene chloride/acetone) afforded 0.15 g of 5-[3-(6-Bromo-1,1-dioxo-3,4-dihydro-1H-1lambda*6*-benzo[e][1,2]thiazin-2-yl)-2-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-1H-pyridin-2-one as a pale solid MS (ESI) 796.2 (M+H)+.
CC(C)(C)[SiH2]OC(C)(C)c1c(-c2c[nH]c(=O)c(Nc3ccc(C(=O)N4CCOCC4)cn3)c2)cccc1N1CCc2cc(Br)ccc2S1(=O)=O
null
O=S(=O)(Cl)c1ccc(Br)cc1CCBr
Cn1cc(-c2cccc(N)c2C(C)(C)O[SiH2]C(C)(C)C)cc(Nc2ccc(C(=O)N3CCOCC3)cn2)c1=O
null
[NH2:1][C:2]1[C:3]([C:31]([CH3:39])([CH3:38])[O:32][SiH2:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[C:4]([C:8]2[CH:9]=[C:10]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[O:24])=[CH:19][N:18]=3)[C:11](=[O:15])[N:12](C)[CH:13]=2)[CH:5]=[CH:6][CH:7]=1.[Br:40][C:41]1[CH:46]=[CH:45][C:44]([S:47](Cl)(=[O:49])=[O:48])=[C:43]([CH2:51][CH2:52]Br)[CH:42]=1.CCN(C(C)C)C(C)C>ClC(Cl)C>[Br:40][C:41]1[CH:46]=[CH:45][C:44]2[S:47](=[O:49])(=[O:48])[N:1]([C:2]3[C:3]([C:31]([CH3:39])([CH3:38])[O:32][SiH2:33][C:34]([CH3:36])([CH3:35])[CH3:37])=[C:4]([C:8]4[CH:9]=[C:10]([NH:16][C:17]5[CH:22]=[CH:21][C:20]([C:23]([N:25]6[CH2:26][CH2:27][O:28][CH2:29][CH2:30]6)=[O:24])=[CH:19][N:18]=5)[C:11](=[O:15])[NH:12][CH:13]=4)[CH:5]=[CH:6][CH:7]=3)[CH2:52][CH2:51][C:43]=2[CH:42]=1
null
CCN(C(C)C)C(C)C
CC(Cl)Cl
null
null
null
53.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
309,877
Cl
null
null
null
ord_dataset-081613ef79bd4110aacc146b4465f086
1995-01-01T00:05:00
true
To 5 ml of a methylene chloride solution of 149 mg of 2-[(1R,2S)-2-{(S)-2-cyclohexylmethoxycarbonylamino-4-methylvalerylamino}-1-hydroxy-3-methylbutyl]-3-phenylcyclopropenone obtained in Example 2 were added 81 mg of acetyl chloride and 102 mg of triethylamine. The resultant mixture was stirred at room temperature for 3 hours, mixed with diluted hydrochloric acid and shaken with methylene chloride. The organic layer was washed with water, saturated aqueous sodium bicarbonate and saturated brine in that order, dried over magnesium sulfate and filtered. The filtrate was concentrated and chromatographed on a column of silica gel, eluting with hexane:ethyl acetate (1:1) to give 73 mg of the titled product.
CC(=O)O[C@H](c1c(-c2ccccc2)c1=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)OCC1CCCCC1)C(C)C
null
CC(C)C[C@H](NC(=O)OCC1CCCCC1)C(=O)N[C@@H](C(C)C)[C@H](O)c1c(-c2ccccc2)c1=O
CC(=O)Cl
null
[CH:1]1([CH2:7][O:8][C:9]([NH:11][C@@H:12]([CH2:32][CH:33]([CH3:35])[CH3:34])[C:13]([NH:15][C@@H:16]([CH:29]([CH3:31])[CH3:30])[C@@H:17]([C:19]2[C:20](=[O:28])[C:21]=2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[OH:18])=[O:14])=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:36](Cl)(=[O:38])[CH3:37].Cl>C(Cl)Cl.C(N(CC)CC)C>[C:36]([O:18][C@H:17]([C:19]1[C:20](=[O:28])[C:21]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C@@H:16]([NH:15][C:13](=[O:14])[C@@H:12]([NH:11][C:9]([O:8][CH2:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:10])[CH2:32][CH:33]([CH3:35])[CH3:34])[CH:29]([CH3:30])[CH3:31])(=[O:38])[CH3:37]
null
ClCCl
CCN(CC)CC
null
null
45.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
747,806
[Na+]
[OH-]
null
null
ord_dataset-4b705442211b4a3988e26d5f65098160
2006-01-01T00:12:00
true
8.26 g (19.5 mmol) of the benzyl ester from example 1 were dissolved in 100 ml THF and stirred overnight with 20 ml 2 M aqueous NaOH. The solvent was removed after filtration, water was added, and the solution extracted with diethyl ether. The aqueous phase was freeze dried and sufficiently pure for further derivatization.
N=C(N)c1ccc(NC(=O)C(C(=O)[O-])c2ccccc2)cc1
null
N=C(N)c1ccc(NC(=O)C(C(=O)OCc2ccccc2)c2ccccc2)cc1
null
null
C([O:8][C:9](=[O:29])[CH:10]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:11]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([C:20](=[NH:22])[NH2:21])=[CH:16][CH:15]=1)=[O:12])C1C=CC=CC=1.[OH-].[Na+:31]>C1COCC1>[Na+:31].[C:20]([C:17]1[CH:16]=[CH:15][C:14]([NH:13][C:11](=[O:12])[CH:10]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:9]([O-:29])=[O:8])=[CH:19][CH:18]=1)(=[NH:21])[NH2:22]
null
C1CCOC1
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
454,956
Cl
[Na+]
[OH-]
null
ord_dataset-4a5b4fffffb34daa876fff1f127a4135
2000-01-01T00:01:00
true
A mixture of Compound B (200 mg, 0.63 mmol), dichloromethane (5 mL), and aqueous sodium hydroxide (1 ml, 1N) was combined and cooled to 0° C. Acetyl chloride (66 mL, 0.94 mmol) was added to the mixture, and after stirring for 2 hour at 0° C. aqueous sodium hydroxide (20 ml, 1N) and dichloromethane (50 mL) were added, followed by extraction with dichloromethane (50 mL). The organic portions were combined, dried (Na2SO4), and concentrated to a crude oil (230 mg, 100%).
CC(=O)N1Cc2cc(Br)ccc2NCC1Cc1ccccc1
null
CC(=O)Cl
O=C(c1cccc2ccccc12)N1CCN(Cc2c[nH]cn2)c2ccc(Br)cc2C1
null
Cl.[Br:2][C:3]1[CH:4]=[CH:5][C:6]2[N:12]([CH2:13]C3N=CNC=3)[CH2:11][CH2:10][N:9]([C:19]([C:21]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)C=CC=3)=O)[CH2:8][C:7]=2[CH:31]=1.[OH-].[Na+].C(Cl)(=[O:36])C>ClCCl>[C:10]([N:9]1[CH2:8][C:7]2[CH:31]=[C:3]([Br:2])[CH:4]=[CH:5][C:6]=2[NH:12][CH2:13][CH:19]1[CH2:21][C:30]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)(=[O:36])[CH3:11]
null
ClCCl
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
80,381
[K+]
[Na+]
[OH-]
null
ord_dataset-2d589ad46f82417ab9ddc07f7655411c
1981-01-01T00:04:00
true
4-Methylphenacyl bromide (XVI: X=Br) (63 g, 0.296 mole), 4-nitrophenol (XI) (42.4 g, 0.305 mole) and potassium hydroxide (22.5 g, 0.4 mole) were added to methanol (300 ml), and the mixture was heated under reflux for 4 hours. Thereafter, the reaction mixture was treated in the same manner as in Example 29 to obtain 50.0 g of 4-methyl-α-(4-nitrophenoxy)acetophenone (XII) (yield, 62.3%).
CC1([N+](=O)[O-])C=CC(OCC(=O)c2ccccc2)=CC1
null
Cc1ccc(C(=O)CBr)cc1
O=[N+]([O-])c1ccc([O-])cc1
CO
C[C:2]1[CH:11]=[CH:10][C:5]([C:6](=[O:9])[CH2:7]Br)=[CH:4][CH:3]=1.O.O.[N+:14]([C:17]1[CH:22]=[CH:21][C:20]([O-:23])=[CH:19][CH:18]=1)([O-:16])=[O:15].[Na+].[OH-].[K+].[CH3:27]O>>[CH3:27][C:17]1([N+:14]([O-:16])=[O:15])[CH:22]=[CH:21][C:20]([O:23][CH2:7][C:6]([C:5]2[CH:4]=[CH:3][CH:2]=[CH:11][CH:10]=2)=[O:9])=[CH:19][CH2:18]1
null
O
null
null
null
62.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
845,204
[Na+]
null
null
null
ord_dataset-e2b35e721c2741999b0005d12691f9fe
2008-01-01T00:10:00
true
Treatment of (±)-[7-(4-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (1.01 g, 2.56 mmol) with sodium azide (0.664 g, 10.24 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2-(azidomethyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzofuran. Treatment of the azide with palladium on carbon (0.03 g, 10 wt. %) generally according to the procedure described for Example 1 provided 0.528 g (75%) of (±)-1-[7-(4-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt. mp 231-232° C.; Anal. calcd. for C16H17NOHCl: C, 69.69; H, 6.58; N, 5.08. Found: C, 66.26; H, 7.0; N, 4.73.
Cc1ccc(-c2cccc3c2OC(CN=[N+]=[N-])C3)cc1
null
Cc1ccc(-c2cccc3c2OC(COS(=O)(=O)c2ccc(C)cc2)C3)cc1
[N-]=[N+]=[N-]
null
CC1C=CC(S(O[CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21]([C:22]4[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=4)[C:15]=3[O:14]2)(=O)=O)=CC=1.[N-:29]=[N+:30]=[N-:31].[Na+]>>[N:29]([CH2:12][CH:13]1[CH2:17][C:16]2[CH:18]=[CH:19][CH:20]=[C:21]([C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=3)[C:15]=2[O:14]1)=[N+:30]=[N-:31]
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
1,215,314
[Li+]
null
null
null
ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777
2012-01-01T00:10:00
true
Following general procedure Z3 followed by C, starting from 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-ylmethyl]-1H-pyrazol-4-ylamine and 5-(6-methyl-pyridin-2-yl)-oxazole-4-carboxylic acid lithium salt. LC-MS-conditions 02: tR=0.75 min; [M+H]+=392.31.
CC(=O)c1ccc(Cn2cc(NC(=O)c3ncoc3-c3cccc(C)n3)cn2)o1
null
Cc1cccc(-c2ocnc2C(=O)[O-])n1
CC1(c2ccc(Cn3cc(N)cn3)o2)OCCO1
null
[CH3:1][C:2]1([C:7]2[O:11][C:10]([CH2:12][N:13]3[CH:17]=[C:16]([NH2:18])[CH:15]=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[Li+].[CH3:20][C:21]1[N:26]=[C:25]([C:27]2[O:31][CH:30]=[N:29][C:28]=2[C:32]([O-])=[O:33])[CH:24]=[CH:23][CH:22]=1>>[C:2]([C:7]1[O:11][C:10]([CH2:12][N:13]2[CH:17]=[C:16]([NH:18][C:32]([C:28]3[N:29]=[CH:30][O:31][C:27]=3[C:25]3[CH:24]=[CH:23][CH:22]=[C:21]([CH3:20])[N:26]=3)=[O:33])[CH:15]=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[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
1,708,537
CCCC[N+](CCCC)(CCCC)CCCC
[F-]
[Li+]
null
ord_dataset-54347fcace774f89850681d6dec8009f
2016-01-01T00:03:00
true
(5R,6S)-1-((S)-1-(Tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-ethylpiperidin-2-one (421 mg, 0.639 mmol; Example 202, Step A) was azeotroped with toluene (3×). THF (1.6 mL) was added. The mixture was sparged with argon for 5 minutes and then cooled to 0° C. 1.0 M lithium diisopropylamide solution in THF (1.246 mL, 1.246 mmol) was added dropwise. After 25 minutes, allyl bromide (0.166 mL, 1.917 mmol) was added dropwise. After 20 minutes, the mixture was quenched with sat. aq. NH4Cl solution. The mixture was extracted with ethyl acetate. The organic layer was washed with sat. aq. NaCl solution, dried over Na2SO4, and concentrated. The residue was dissolved in THF (3 mL) and 1.0M tetrabutylammonium fluoride solution in THF (2.335 mL, 2.335 mmol) was added. After stirring overnight, the mixture was partitioned between 5% aq. HCl and ethyl acetate. The organic layer was washed with sat. aq. NaCl solution, dried over Na2SO4, and concentrated. The residue was purified by flash chromatography on silica gel (eluent: 20 to 50% ethyl acetate/hexanes) to afford the title compound as the more polar major diastereomer.
C=CCC1(CC)C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)N([C@@H](CC)CO)C1=O
null
CC(C)[N-]C(C)C
CCC1C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)N([C@@H](CC)CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)C1=O
null
[Si]([O:18][CH2:19][C@@H:20]([N:23]1[C@H:28]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)[C@@H:27]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=2)[CH2:26][CH:25]([CH2:43][CH3:44])[C:24]1=[O:45])[CH2:21][CH3:22])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[CH:46]([N-]C(C)C)([CH3:48])[CH3:47].[Li+].C(Br)C=C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.C1(C)C=CC=CC=1>[CH2:48]([C:25]1([CH2:43][CH3:44])[CH2:26][C@H:27]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=2)[C@@H:28]([C:29]2[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=2)[N:23]([C@@H:20]([CH2:21][CH3:22])[CH2:19][OH:18])[C:24]1=[O:45])[CH:46]=[CH2:47]
0.42
C1CCOC1
Cc1ccccc1
C=CCBr
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
535,384
[BH3-]C#N
[Na+]
null
null
ord_dataset-1884c7bf3d544afdb8d17b5d41b90a27
2002-01-01T00:03:00
true
To a solution of 2-amino-5-chloro-α-(3-tert-butoxycarbonylaminomethylphenyl)benzyl alcohol (0.7 g) in methanol (7 ml) were added benzaldehyde (229 mg) and acetic acid (130 mg). The mixture was stirred for 10 minutes at room temperature, to which was added sodium cyano-borohydride (135 mg). The mixture was stirred for 30 minutes at room temperature, to which was added ethyl acetate ester (50 ml). The mixture was washed with water and dried over anhydrous MgSO4, followed by distilling off the solvent. The residue was purified by means of a silica gel column chromatography to give the object 2-benzylamino-5-chloro-α-(3-tert-butoxycarbonylaminomethylphenyl)benzyl alcohol (0.91 g) as a colorless oily compound.
CC(C)(C)OC(=O)NCc1cccc(C(O)c2cc(Cl)ccc2NCc2ccccc2)c1
null
CC(C)(C)OC(=O)NCc1cccc(C(O)c2cc(Cl)ccc2N)c1
O=Cc1ccccc1
null
[NH2:1][C:2]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:3]=1[CH:4]([OH:20])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:6]=1.[CH:26](=O)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO.C(OCC)(=O)C>[CH2:26]([NH:1][C:2]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:3]=1[CH:4]([OH:20])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][NH:12][C:13]([O:15][C:16]([CH3:18])([CH3:19])[CH3:17])=[O:14])[CH:6]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
0.17
CO
CCOC(C)=O
CC(=O)O
25
null
104.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,567,731
CN(C)C(On1nnc2ccccc21)=[N+](C)C
F[P-](F)(F)(F)(F)F
null
null
ord_dataset-9741bb5fd93044078df2a45f45733054
2015-01-01T00:04:00
true
To a mixture of tert-butyl piperazine-1-carboxylate (1.81 g, 9.7 mmol), 3-fluoro-4-methylbenzoic acid (1.50 g, 9.7 mmol), and triethylamine (6.8 mL, 49 mmol) in acetnitrile (30 mL), HBTU (4.06 g, 10.7 mmol) was added. After stirring at rt for 1 h, the mixture was poured onto water (150 mL), and the mixture was extracted with EtOAc (twice). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with hexane/EtOAc (4:1-2:1) to give 3.14 g (quant) of the title compound as a white solid.
Cc1ccc(C(=O)N2CCN(C(=O)OC(C)(C)C)CC2)cc1F
null
Cc1ccc(C(=O)O)cc1F
CC(C)(C)OC(=O)N1CCNCC1
null
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[F:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[CH3:24])[C:18](O)=[O:19].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(#N)C>[F:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[CH3:24])[C:18]([N:4]1[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]1)=[O:19]
1
CC#N
CCN(CC)CC
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
1,225,838
null
null
null
null
ord_dataset-cde802cdb7434a5f82a22981ccaefc4e
2012-01-01T00:11:00
true
To 4-[4-(tert-butyldimethylsilanyloxy)butyl]-1-trityl-1H-imidazole (3.95 g, 7.95 mmol) is added acetonitrile (300 mL). To this solution is added 3-bromo-4-bromomethylbenzonitrile (2.14 g, 7.78 mmol). The solution is stirred at 40° C. for 18 h. The solvent is then removed in vacuo and methanol (300 ml) is added. The solution is heated to 55° C. and stirred for 1.5 h. Saturated sodium bicarbonate is then added and stirred for 10 min. The organic solvent is removed in vacuo, and the crude product extracted into ethyl acetate and washed with water. The organic solvent is removed in vacuo to give the crude product. Chromatography (silica gel, 1:0 to 1:1 to 0:1 hexanes:ethyl acetate) gives the pure product. MS (ESI) m/z 448, 450 (M+H).
CC(C)(C)[Si](C)(C)OCCCCc1cn(Cc2ccc(C#N)cc2Br)cn1
null
CC(C)(C)[Si](C)(C)OCCCCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
N#Cc1ccc(CBr)c(Br)c1
null
[Si:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]1[N:14]=[CH:15][N:16](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:17]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(#N)C.[Br:40][C:41]1[CH:42]=[C:43]([CH:46]=[CH:47][C:48]=1[CH2:49]Br)[C:44]#[N:45]>C(OCC)(=O)C>[Br:40][C:41]1[CH:42]=[C:43]([CH:46]=[CH:47][C:48]=1[CH2:49][N:16]1[CH:17]=[C:13]([CH2:12][CH2:11][CH2:10][CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[N:14]=[CH:15]1)[C:44]#[N:45]
18
CCOC(C)=O
CC#N
null
40
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
493,560
null
null
null
null
ord_dataset-3f9174c7efcb4f31becbd3516cde9572
2001-01-01T00:02:00
true
In an analogous manner to that described in Example 5, from 7-chloro-5-methyl-2-methylsulphanyl-3-(toluene-4-sulphonyl) -pyrazolo[1,5-a]pyrimidine and dimethylamine in EtOH there was obtained dimethyl-[5-methyl-2-methylsulphanyl-3-(toluene-4-sulphonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-amine as colorless crystals, m.p. >230°.
CSc1nn2c(N(C)C)cc(C)nc2c1S(=O)(=O)c1ccc(C)cc1
null
CSc1nn2c(Cl)cc(C)nc2c1S(=O)(=O)c1ccc(C)cc1
CNC
null
Cl[C:2]1[N:7]2[N:8]=[C:9]([S:21][CH3:22])[C:10]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])=[C:6]2[N:5]=[C:4]([CH3:23])[CH:3]=1.[CH3:24][NH:25][CH3:26]>CCO>[CH3:24][N:25]([CH3:26])[C:2]1[N:7]2[N:8]=[C:9]([S:21][CH3:22])[C:10]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])=[C:6]2[N:5]=[C:4]([CH3:23])[CH:3]=1
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
419,878
On1nnc2ccccc21
null
null
null
ord_dataset-94e21e9990034c729ea727e7d2ab0eb0
1998-01-01T00:12:00
true
With the exclusion of air, 270 mg (1.43 mmol) of N-methoxycarbonyl-(L)-iso-leucine, 513 mg (2.67 mmol) of EDC and 241 mg (1.78 mmol) of HOBT are dissolved in 7.8 ml of DMF. After stirring for 15 min, 0.75 ml (5.4 mmol) of TEA and 510 mg (0.89 mmol) of 1-{4-[2-(1-methyl -1-phenyl-ethyl)-2H-tetrazol-5-yl]-phenyl}-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexane (Example 25f) in 3.7 ml of DMF are added. After 20 hours, the mixture is worked up analogously to Example 25g to yield the title compound: HPLC20-100 : tRet =18.5; FAB MS (M+H)+ =743.
CC[C@H](C)[C@H](NC(=O)OC)C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)CN(Cc1ccc(-c2nnn(C(C)(C)c3ccccc3)n2)cc1)NC(=O)OC(C)(C)C
null
CC[C@H](C)[C@H](NC(=O)OC)C(=O)O
CC(C)(C)OC(=O)NN(Cc1ccc(-c2nnn(C(C)(C)c3ccccc3)n2)cc1)C[C@H](O)[C@@H](N)Cc1ccccc1
null
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:11]([OH:13])=O)[C@H:7]([CH2:9][CH3:10])[CH3:8])=[O:4].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:28][C:29]([N:37]1[N:41]=[N:40][C:39]([C:42]2[CH:47]=[CH:46][C:45]([CH2:48][N:49]([NH:62][C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[CH2:50][C@H:51]([OH:61])[C@@H:52]([NH2:60])[CH2:53][C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[CH:44][CH:43]=2)=[N:38]1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:30]>CN(C=O)C>[CH3:30][C:29]([N:37]1[N:41]=[N:40][C:39]([C:42]2[CH:47]=[CH:46][C:45]([CH2:48][N:49]([NH:62][C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[CH2:50][C@H:51]([OH:61])[C@@H:52]([NH:60][C:11](=[O:13])[C@H:6]([C@H:7]([CH2:9][CH3:10])[CH3:8])[NH:5][C:3]([O:2][CH3:1])=[O:4])[CH2:53][C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[CH:44][CH:43]=2)=[N:38]1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:28]
0.25
ClCCCl
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
914,550
CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C
CN(C1CCCCC1)C1CCCCC1
null
null
ord_dataset-c663259b80f947e2a8923796fb0e9a6b
2009-01-01T00:10:00
true
A solution of 10.0 g (51.0 mmol) of 4-bromo-2-methylbenzonitrile in 80 mL of 1,4-dioxane was treated with 7.19 g (56.1 mmol) of tert-butyl acrylate, 10.96 g (56.1 mol) of N-methyldicyclohexylamine, 228 mg (0.76 mol) of 2-(di-tert-butylphosphino) biphenyl, and 396 mg (0.38 mol) of tris(dibenzylideneacetone)dipalladium(0)-chloroforin adduct. The resulting mixture was heated at 70° C. for 16 h and cooled to rt. The reaction mixture was filtered though a filter paper, and the filtrate was concentrated. The crude product was partitioned into four portions. Chromatography on four Biotage 40M cartridges using 19:1 v/v hexanes/EtOAc as the eluant followed by pooling of product fractions afforded 10.0 g of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.55 (s, 9H), 2.58 (s, 3H), 6.44 (d, J=16.0, 1H), 7.41 (d, J=8.0, 1H), 7.45 (s, 1H), 7.53 (d, J=16.0, 1H), 7.61 (d, J=8.0, 1H).
Cc1cc(C=CC(=O)OC(C)(C)C)ccc1C#N
null
C=CC(=O)OC(C)(C)C
Cc1cc(Br)ccc1C#N
null
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([CH3:10])[CH:3]=1.[C:11]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])(=[O:14])[CH:12]=[CH2:13].CN(C1CCCCC1)C1CCCCC1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>O1CCOCC1>[CH3:10][C:4]1[CH:3]=[C:2]([CH:13]=[CH:12][C:11]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:9]=[CH:8][C:5]=1[C:6]#[N:7]
null
C1COCCO1
null
null
70
null
80.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,696,816
null
null
null
null
ord_dataset-54347fcace774f89850681d6dec8009f
2016-01-01T00:03:00
true
The title compound or its salt was prepared by a procedure similar to that described for E59 starting from (2,3-difluorophenyl)methanamine and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.
CN1CCCn2c1cc(NCc1cccc(F)c1F)nc2=O
null
CN1CCCn2c1cc(Cl)nc2=O
NCc1cccc(F)c1F
null
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][NH2:10].Cl[C:12]1[CH:22]=[C:16]2[N:17]([CH3:21])[CH2:18][CH2:19][CH2:20][N:15]2[C:14](=[O:23])[N:13]=1>>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][NH:10][C:12]1[CH:22]=[C:16]2[N:17]([CH3:21])[CH2:18][CH2:19][CH2:20][N:15]2[C:14](=[O:23])[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
107,824
null
null
null
null
ord_dataset-29d79fca4cec4a43b773d0ba25b27651
1983-01-01T00:08:00
true
To a solution of benzhydryl 7-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-imidazolyl)carbonyloxymethyl-3-cephem-4-carboxylate (syn isomer) (13.5 g) in tetrahydrofuran (200 ml) was added m-chloroperbenzoic acid (5.8 g) with stirring under ice-cooling, followed by stirring for an hour at 5° C. The reaction mixture was evaporated and the residue was pulverized in diethyl ether, collected by filtration, washed with ethyl acetate and diethyl ether and then dried to give benzhydryl 7-[2-methoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-imidazolyl)carbonyloxymethyl-3-cephem-4-carboxylate-1-oxide (syn isomer) (11.0 g).
CON=C(C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(COC(=O)n3ccnc3)CS(=O)[C@H]12)c1csc(NC=O)n1
null
O=C(OO)c1cccc(Cl)c1
CON=C(C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(COC(=O)n3ccnc3)CS[C@H]12)c1csc(NC=O)n1
null
[CH3:1][O:2][N:3]=[C:4]([C:42]1[N:43]=[C:44]([NH:47][CH:48]=[O:49])[S:45][CH:46]=1)[C:5]([NH:7][CH:8]1[C:40](=[O:41])[N:10]2[C:11]([C:24]([O:26][CH:27]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])=[C:12]([CH2:15][O:16][C:17]([N:19]3[CH:23]=[CH:22][N:21]=[CH:20]3)=[O:18])[CH2:13][S:14][C@H:9]12)=[O:6].ClC1C=CC=C(C(OO)=[O:58])C=1>O1CCCC1>[CH3:1][O:2][N:3]=[C:4]([C:42]1[N:43]=[C:44]([NH:47][CH:48]=[O:49])[S:45][CH:46]=1)[C:5]([NH:7][CH:8]1[C:40](=[O:41])[N:10]2[C:11]([C:24]([O:26][CH:27]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])=[C:12]([CH2:15][O:16][C:17]([N:19]3[CH:23]=[CH:22][N:21]=[CH:20]3)=[O:18])[CH2:13][S:14](=[O:58])[C@H:9]12)=[O:6]
null
C1CCOC1
null
null
null
79.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
296,717
CCCC[N+](CCCC)(CCCC)CCCC
Cl
[F-]
null
ord_dataset-ec7cb3d5a8704f64b01d401ea555974f
1994-01-01T00:09:00
true
The 1-[3-[(1,1-dimethylethyl)dimethylsiloxy]phenyl]-2-[(dimethylamino)methylene]-2-(4,5-diphenyl-2-oxazolyl)ethanone (19) (10.3 g, 19.6 mmol) was dissolved in THF (100 mL) and tetra-n-butyl ammonium fluoride (17.5 mL of 1M in THF) was added dropwise. The reaction mixture was stirred for about 1/4 hour and poured onto an ether (180 mL)/1N HCl(20 mL) solution, and the organic phase separated and dried (MgSO4). Chromatography (elution with 75% ethyl acetate/hexanes) gave the phenol 7.7 g (96%). IR (KBr, cm-1) 3170, 3060, 2920, 1735, 1635, 1600, 1447, 1375, 1310, 1210, 1010, 965, 870, 765, 695. 1H NMR (300 MHz, CDCl3) δ 2.6 to 3.1 (6H, Series of Br. s) 6.84 (1H, Br.s), 6.95 (1H, Br. s), 7.04 to 7.24 (10H, m), 7.32 to 7.60 (5H, m). m/e 411 (MH+)
CN(C)C=C(C(=O)c1cccc(O)c1)c1nc(-c2ccccc2)c(-c2ccccc2)o1
null
CN(C)C=C(C(=O)c1cccc(O[Si](C)(C)C(C)(C)C)c1)c1nc(-c2ccccc2)c(-c2ccccc2)o1
null
null
CC([Si](C)(C)[O:6][C:7]1[CH:8]=[C:9]([C:13](=[O:36])[C:14](=[CH:32][N:33]([CH3:35])[CH3:34])[C:15]2[O:16][C:17]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:19]=2)[CH:10]=[CH:11][CH:12]=1)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOCC.Cl>C1COCC1>[OH:6][C:7]1[CH:8]=[C:9]([C:13](=[O:36])[C:14](=[CH:32][N:33]([CH3:35])[CH3:34])[C:15]2[O:16][C:17]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:19]=2)[CH:10]=[CH:11][CH:12]=1
null
C1CCOC1
CCOCC
null
null
null
95.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,003,677
[Pd+2]
[OH-]
null
null
ord_dataset-70899a0178cc441482746c093624afa0
2010-01-01T00:10:00
true
A mixture of 4-benzyloxycarbonyl-1-(4-fluorobenzyl)-3,4-dihydro-pyrazin-2(1H)-one (0.5 g, 1.45 mmol) and Pearlman's catalyst (26 mg; 20% palladium hydroxide on carbon) in methanol (25 mL) was stirred under an atmosphere of hydrogen (1 atm) at room temperature overnight. The product mixture was filtered through a pad of Celite, and concentrated under vacuum to provide 1-(4-fluorobenzyl)piperazin-2-one. 1H NMR (400 MHz, d6 DMSO) δ 7.29 (dd, J=8.4, 5.7 Hz, 2H), 7.16 (t, J=9.0 Hz, 2H), 4.48 (s, 2H), 3.28 (s, 2H), 3.14 (t, J=5.3 Hz, 2H) 2.84 (t, J=5.3 Hz, 2H); ES MS (M+1)=209.
O=C1CNCCN1Cc1ccc(F)cc1
null
O=C1CN(C(=O)OCc2ccccc2)C=CN1Cc1ccc(F)cc1
null
null
C(OC([N:11]1[CH:16]=[CH:15][N:14]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[C:13](=[O:25])[CH2:12]1)=O)C1C=CC=CC=1>[OH-].[OH-].[Pd+2].CO>[F:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][N:14]2[CH2:15][CH2:16][NH:11][CH2:12][C:13]2=[O:25])=[CH:19][CH:20]=1
8
CO
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
533,508
CCCC[N+](CCCC)(CCCC)CCCC
O=S(=O)([O-])O
[K+]
null
ord_dataset-b1a34bc8c1204d51a772ed27396c794e
2002-01-01T00:02:00
true
A solution of potassium peroxymonosulfate (4.1 g) in water (21 ml) was added dropwise to a mixture of ethyl 2,3-dihydro-7-methylthio-1-benzoxepin-4-carboxylate (0.8 g) and tetrabutylammonium hydrogen sulfate (0.2 g) in ethyl acetate (8 ml) and water (4 ml) at ambient temperature and the mixture was stirred at the same temperature for 3 hours. The separated organic layer was washed with 10% aqueous sodium thiosulfate. The organic layer was washed with water, dried over magnesium sulfate and evaporated in vacuo to give ethyl 2,3-dihydro-7-methanesulfonyl-1-benzoxepin-4-carboxylate (0.77 g).
CCOC(=O)C1=Cc2cc(S(C)(=O)=O)ccc2OCC1
null
O=S(=O)([O-])O[O-]
O
CCOC(=O)C1=Cc2cc(SC)ccc2OCC1
S([O-])(O[O-])(=O)=[O:2].[K+].[K+].[CH3:9][S:10][C:11]1[CH:12]=[CH:13][C:14]2[O:20][CH2:19][CH2:18][C:17]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:16][C:15]=2[CH:26]=1.[OH2:27]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[CH3:9][S:10]([C:11]1[CH:12]=[CH:13][C:14]2[O:20][CH2:19][CH2:18][C:17]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:16][C:15]=2[CH:26]=1)(=[O:2])=[O:27]
3
CCOC(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
245,973
Cl
null
null
null
ord_dataset-5eb2900a93c842ee98f26c305e657b61
1992-01-01T00:04:00
true
To a dispersion of 1.51 g of 2-mercaptoimidazo[4,5-b]pyridine in 25 ml of ethanol was added at once 1.92 g of 2-(methylamino)benzyl chloride hydrochloride at room temperature under stirring. The resulting mixture was further stirred for 3.5 hours. The precipitated crystals were collected by filtration and washed with ethanol. The obtained crystals were added portionwise to a mixture of 100 ml of chloroform and 100 ml of 1N NaOH solution for neutralization. The aqueous NaOH phase was separated, and to this phase were successively added 200 ml of chloroform and a saturated ammonium chloride solution until the aqueous phase showed no turbidity upon addition of the solution. The chloroform phase was separated, washed with a saturated aqueous sodium chloride solution, and dried over sodium sulfate. The solvent was then distilled off under reduced pressure and the residue was crystallized by addition of diethyl ether. The crystalline product was collected by filtration and dried to give 1.84 g (yield: 68.1%) of 2-[2-(methylamino)benzylthio]imidazo[4,5-b]pyridine as a white crystalline powder.
CNc1ccccc1CSc1nc2ncccc2[nH]1
null
CNc1ccccc1CCl
Sc1nc2ncccc2[nH]1
null
[SH:1][C:2]1[NH:3][C:4]2[C:5]([N:10]=1)=[N:6][CH:7]=[CH:8][CH:9]=2.Cl.[CH3:12][NH:13][C:14]1[CH:21]=[CH:20][CH:19]=[CH:18][C:15]=1[CH2:16]Cl>C(O)C>[CH3:12][NH:13][C:14]1[CH:21]=[CH:20][CH:19]=[CH:18][C:15]=1[CH2:16][S:1][C:2]1[NH:3][C:4]2[C:5]([N:10]=1)=[N:6][CH:7]=[CH:8][CH:9]=2
null
CCO
null
null
null
68.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,092,854
null
null
null
null
ord_dataset-52a37d876ddb453e86de0c15fa233d29
2011-01-01T00:09:00
true
Ethoxycarbonyl isothiocyanate (0.5 ml, 4.18 mmol) was added to a solution of 4-[(quinolin-4-ylmethyl)amino]-1H-imidazole-4-carboxamide (0.93 g, crude material from Example 24(a)) dissolved in anhydrous dichloromethane (10 mL) and methanol (5 mL) mixture. After o.n. (over night) at r.t., the solution was concentrated in vacuo and the residue was dissolved in 1N NaOH solution (30 mL) and refluxed for 3.5 h. After cooling to r.t., the pH was adjusted to ˜6.5 with 2 N HCl. The solid that formed was collected by filtration and dried generating 0.35 g of crude material. A portion of the solid (150 mg) was purified by preparative HPLC, and the solid obtained was washed with dichloromethane and ether, generating 25.9 mg (9% yield over two steps) of the title compound.
O=c1[nH]c(=S)n(Cc2ccnc3ccccc23)c2nc[nH]c12
null
CCOC(=O)N=C=S
NC(=O)C1(NCc2ccnc3ccccc23)CNC=N1
null
C(O[C:4]([N:6]=[C:7]=[S:8])=[O:5])C.[N:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([CH2:19][NH:20][C:21]2(C(N)=O)[CH2:25][NH:24][CH:23]=[N:22]2)=[CH:11][CH:10]=1.CO>ClCCl>[N:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([CH2:19][N:20]2[C:21]3[N:22]=[CH:23][NH:24][C:25]=3[C:4](=[O:5])[NH:6][C:7]2=[S:8])=[CH:11][CH:10]=1
null
CO
ClCCl
null
25
9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,496,232
null
null
null
null
ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2
2014-01-01T00:10:00
true
The title compound was prepared by a procedure similar to that described for E1 starting from 2-{[4-chloro-3-(trifluoromethyl)phenyl]oxy}-5-{[(2-oxo-2,3-dihydro-4-pyrimidinyl)oxy]methyl}benzonitrile and bromoethane. LC-MS (ESI): m/z 450 [M+H]+; 4.11 min (ret time).
CCn1ccc(OCc2ccc(Oc3ccc(Cl)c(C(F)(F)F)c3)c(C#N)c2)nc1=O
null
CCBr
N#Cc1cc(COc2ccnc(=O)[nH]2)ccc1Oc1ccc(Cl)c(C(F)(F)F)c1
null
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:16]=[CH:15][C:14]([CH2:17][O:18][C:19]3[NH:20][C:21](=[O:25])[N:22]=[CH:23][CH:24]=3)=[CH:13][C:10]=2[C:11]#[N:12])=[CH:4][C:3]=1[C:26]([F:29])([F:28])[F:27].Br[CH2:31][CH3:32]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:16]=[CH:15][C:14]([CH2:17][O:18][C:19]3[CH:24]=[CH:23][N:22]([CH2:31][CH3:32])[C:21](=[O:25])[N:20]=3)=[CH:13][C:10]=2[C:11]#[N:12])=[CH:4][C:3]=1[C:26]([F:27])([F:29])[F:28]
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