Datasets:
Azzindani
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Open_Reaction_Data

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original_index
int64
2
1.77M
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489 values
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1976-01-01 00:01:00
2016-01-01 00:09:00
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bool
1 class
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8
24.5k
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solvent_000
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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
1,170,350
null
null
null
null
ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880
2012-01-01T00:05:00
true
In Scheme 2, Step A, the phthalimide group of the tetrahydrocyclopenta[b]indole of formula (2) is cleaved with methylamine to provide an aminotetrahydrocyclopenta[b]indole of formula (3). Preferred conditions use a solvent such as ethanol at a temperature of about 0 to 35° C., for 3 to 24 hours. The resulting by-product is removed by making the pH alkaline and filtering the resultant precipitate. The product is isolated from the filtrate by precipitation with water and 10% NaOH.
NC1CCC2N=c3ccccc3=C12
null
CN
c1ccc2c(c1)=NC1CCCC=21
null
[CH2:1]1[C:12]2[CH:4]([N:5]=[C:6]3[C:11]=2[CH:10]=[CH:9][CH:8]=[CH:7]3)[CH2:3][CH2:2]1.C[NH2:14]>>[NH2:14][CH:1]1[C:12]2[CH:4]([N:5]=[C:6]3[C:11]=2[CH:10]=[CH:9][CH:8]=[CH:7]3)[CH2:3][CH2:2]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
448,238
C[O-]
[N-]=[N+]=NC(=Cc1ccccc1)C(=O)[O-]
[Na+]
null
ord_dataset-a4f0b79f6b9847168861270b79f84afa
1999-01-01T00:11:00
true
A solution of t-butyl 4-formylbenzoate (8.52 g, 41 mmol) and methyl azidoacetate [M. S. Allen, L. K. Hamaker, A. J. La Loggia, J. M. Cook, Synth. Commun., 1992, 22, 2077-2102] (28.5 g, 248 mmol) in dry MeOH (200 mL) was added dropwise over 1 h to a solution of NaOMe (60 mL of a 3.3M solution in MeOH, 197 mmol) under nitrogen with cooling in an ice-salt bath. The yellow suspension was stirred for a further 1 h at 0° C., allowed to stand at 4° C. for 15 h, then diluted with water and the solid filtered off and dried in the dark. A solution of this crude azidocinnamate (8.76 g, 29 mmol) in dry xylene (400 mL) was added dropwise over 2 h to xylene (100 mL) at ref lux under nitrogen, the solution stirred at reflux for a further 1 h, then cooled and evaporated. Recrystallisation from MeOH gave t-butyl 2-(methoxycarbonyl)indole-6-carboxylate as a white solid (4.72 g, 42%), mp 189-190.5° C. 1H NMR [(CD3)2SO] δ12.26 (s, 1H, NH), 8.08 (s, 1H, H-3 or H-7), 7.73 (d, J=8.4 Hz, 1H, H-4), 7.61 (dd, J=8.4, 1.3 Hz, 1H, H-5), 7.21 (d, J=1.3 Hz, 1H, H-3 or H-7), 3.89 (s, 3H, CO2Me), 1.56 (s, 9H, CO2 tBu); 13C NMR δ165.5 (Co2 tBu), 161.4 (CO2Me), 136.5, 130.0, 129.9, 127.3 (C-2,6,8,9), 121.9, 120.3, 114.4, 107.5 (C-3,4,5,7), 80.4 (OCMe3), 52.1 (OCH3), 27.8 (tBu). Anal. (C15H17NO4) C,H,N.
COC(=O)c1cc2ccc(C(=O)OC(C)(C)C)cc2[nH]1
null
CC(C)(C)OC(=O)c1ccc(C=O)cc1
COC(=O)CN=[N+]=[N-]
null
[CH:1]([C:3]1[CH:15]=[CH:14][C:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[CH:5][CH:4]=1)=O.[N:16]([CH2:19][C:20]([O:22][CH3:23])=[O:21])=[N+]=[N-].C[O-].[Na+].N(C(=CC1C=CC=CC=1)C([O-])=O)=[N+]=[N-]>CO.O.C1(C)C(C)=CC=CC=1>[CH3:23][O:22][C:20]([C:19]1[NH:16][C:15]2[C:3]([CH:1]=1)=[CH:4][CH:5]=[C:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH:14]=2)=[O:21]
1
O
Cc1ccccc1C
CO
0
42
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,292,460
[BH3-]C#N
[Na+]
null
null
ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c
2013-01-01T00:05:00
true
6.55 g of (1S,2S)-6-fluoro-1-isopropyl-2-(2-methylamino-ethyl)-1,2,3,4-tetrahydro-naphthalen-2-ol were dissolved in DCM (138 mL)/AcOH (15 mL). 5.36 g of 3-methoxy-2-methoxymethyl-2-methyl-N-(3-oxo-propyl)-propionamide and 6.39 g of sodium cyanoborohydride were added. The reaction mixture was stirred for 2 h at room temperature, quenched with sat.-NaHCO3 and extracted with DCM. The organic phase was washed with brine, dried over anh. Na2SO4 and concentrated in vacuo. The resulting crude material was purified by CC using DCM/MeOH/NEt3 from 100/0/1 to 40/1/0.4 as eluant to yield 10.57 g of N-(3-{[2-((1S,2S)-6-Fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-ethyl]-methyl-amino}-propyl)-3-methoxy-2-methoxymethyl-2-methyl-propionamide as amber resin.
COCC(C)(COC)C(=O)NCCCN(C)CC[C@@]1(O)CCc2cc(F)ccc2[C@@H]1C(C)C
null
CNCC[C@@]1(O)CCc2cc(F)ccc2[C@@H]1C(C)C
COCC(C)(COC)C(=O)NCCC=O
null
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([CH:12]([CH3:14])[CH3:13])[C@:7]([CH2:16][CH2:17][NH:18][CH3:19])([OH:15])[CH2:6][CH2:5]2.[CH3:20][O:21][CH2:22][C:23]([CH2:32][O:33][CH3:34])([CH3:31])[C:24]([NH:26][CH2:27][CH2:28][CH:29]=O)=[O:25].C([BH3-])#N.[Na+]>C(Cl)Cl.CC(O)=O>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([CH:12]([CH3:13])[CH3:14])[C@:7]([CH2:16][CH2:17][N:18]([CH3:19])[CH2:29][CH2:28][CH2:27][NH:26][C:24](=[O:25])[C:23]([CH2:32][O:33][CH3:34])([CH3:31])[CH2:22][O:21][CH3:20])([OH:15])[CH2:6][CH2:5]2
2
CC(=O)O
ClCCl
null
25
91.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,750,046
null
null
null
null
ord_dataset-60a3e71da3174666a50a61dcfa611a9f
2016-01-01T00:07:00
true
The title compound was synthesized according to the procedure described in example 1 using 2,6-dichloro-quinoline-5-carboxylic acid (1-hydroxy-3methyl-cyclohexylmethyl)-amide, DIPEA and (R)-3-fluoropyrrolidine. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.75 (1H), 7.85 (m, 1H), 7.58 (2H), 7.05 (1H), 5.43-5.56 (1H), 4.16 (s, 1H), 3.89 (m, 2H), 3.70 (m, 1H), 3.55 (m, 1H), 3.26 (m, 2H), 2.44 (m, 2H), 2.06 (m, 2H), 1.85 (m, 2H), 1.74-1.76 (m, 5H), 1.27-1.32 (m, 1H), 0.83 (d, 3H). m/z: 420 [M+H]
CC1CCCC(O)(CNC(=O)c2c(Cl)ccc3nc(N4CC[C@H](F)C4)ccc23)C1
null
CC1CCCC(O)(CNC(=O)c2c(Cl)ccc3nc(Cl)ccc23)C1
F[C@@H]1CCNC1
null
[OH:1][C:2]1([CH2:9][NH:10][C:11]([C:13]2[C:14]3[CH:15]=[CH:16][C:17](Cl)=[N:18][C:19]=3[CH:20]=[CH:21][C:22]=2[Cl:23])=[O:12])[CH2:7][CH2:6][CH2:5][CH:4]([CH3:8])[CH2:3]1.CCN(C(C)C)C(C)C.[F:34][C@@H:35]1[CH2:39][CH2:38][NH:37][CH2:36]1>>[OH:1][C:2]1([CH2:9][NH:10][C:11]([C:13]2[C:14]3[CH:15]=[CH:16][C:17]([N:37]4[CH2:38][CH2:39][C@H:35]([F:34])[CH2:36]4)=[N:18][C:19]=3[CH:20]=[CH:21][C:22]=2[Cl:23])=[O:12])[CH2:7][CH2:6][CH2:5][CH:4]([CH3:8])[CH2:3]1
null
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
null
239,405
[Pd]
null
null
null
ord_dataset-960c6b9c4fc74afd90a3ebf713215626
1991-01-01T00:12:00
true
A solution of 11 (30 mg) in 2 mL of methanol was hydrogenated in the presence of 5% Pd/C (10 mg) for 24 hours. The reaction was monitored by TLC. The suspension was filtered and, after complete evaporation of the solvent and chromatography, pure methyl 1-O-(11-methoxycarbonylundecyl)-2, 4-di-O-acetyl-β-D-glucopyranosuronate (12) was obtained. The 1H NMR data confirmed the complete debenzylation.
COC(=O)CCCCCCCCCCCO[C@@H]1O[C@H](C(=O)OC)[C@@H](OC(C)=O)[C@H](O)[C@H]1OC(C)=O
null
COC(=O)CCCCCCCCCCCO[C@@H]1O[C@H](C(=O)OC)[C@@H](OC(C)=O)[C@H](OCc2ccccc2)[C@H]1OC(C)=O
null
null
[CH3:1][O:2][C:3]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][C@@H:17]1[O:38][C@H:37]([C:39]([O:41][CH3:42])=[O:40])[C@@H:32]([O:33][C:34](=[O:36])[CH3:35])[C@H:23]([O:24]CC2C=CC=CC=2)[C@H:18]1[O:19][C:20](=[O:22])[CH3:21])=[O:4]>CO.[Pd]>[CH3:1][O:2][C:3]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][C@@H:17]1[O:38][C@H:37]([C:39]([O:41][CH3:42])=[O:40])[C@@H:32]([O:33][C:34](=[O:36])[CH3:35])[C@H:23]([OH:24])[C@H:18]1[O:19][C:20](=[O:22])[CH3:21])=[O:4]
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
1,643,731
CC(C)(C#N)N=NC(C)(C)C#N
null
null
null
ord_dataset-bcc0b01d4f58457a8733b10a099f43ba
2015-01-01T00:10:00
true
Add N-bromosuccinimide (1090 g, 6.12 mol) and 2,2′-azo-bis-isobutyronitrile (11.4 g, 0.069 mol) to a 20° C. solution of methyl 5-bromo-2-ethylbenzoate (1296 g, 5.33 mol) in carbon tetrachloride (7 L). Heat to reflux for 4 hours, cool to 20-30° C. and wash with water (10 L), extract the aqueous phase with dichloromethane (5 L), combine the organic layers, and wash with water (10 L), Na2SO3 (5 L) and saturated aqueous sodium chloride. Dry with sodium sulfate, filter, and evaporate under reduced pressure to give the title compound as a pale yellow solid (1791 g, 104% crude). ES/MS m/z: 241 (M−HBr).
COC(=O)c1cc(Br)ccc1C(C)Br
null
O=C1CCC(=O)N1Br
CCc1ccc(Br)cc1C(=O)OC
null
[Br:1]N1C(=O)CCC1=O.[Br:9][C:10]1[CH:11]=[CH:12][C:13]([CH2:20][CH3:21])=[C:14]([CH:19]=1)[C:15]([O:17][CH3:18])=[O:16]>C(Cl)(Cl)(Cl)Cl.N(C(C)(C)C#N)=NC(C)(C)C#N>[Br:9][C:10]1[CH:11]=[CH:12][C:13]([CH:20]([Br:1])[CH3:21])=[C:14]([CH:19]=1)[C:15]([O:17][CH3:18])=[O:16]
null
ClC(Cl)(Cl)Cl
null
null
25
null
104.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,301,234
null
null
null
null
ord_dataset-78c3f723155a4347a902b53bcee1524d
2013-01-01T00:06:00
true
TFA (2 ml) was added to a solution of tert-butyl 9-(1H-imidazol-1-yl)-3-azaspiro[5.5]undecane-3-carboxylate (1.10 g, 3.45 mmol, 1.0 eq.) in MC (10 ml) at 0° C. and the resulting reaction mixture was stirred at 25° C. for 2 h. The solvent was evaporated under reduced pressure and the residue was azeotroped twice with MC to get the desired product.
c1cn(C2CCC3(CCNCC3)CC2)cn1
null
CC(C)(C)OC(=O)N1CCC2(CCC(n3ccnc3)CC2)CC1
null
null
C(O)(C(F)(F)F)=O.[N:8]1([CH:13]2[CH2:30][CH2:29][C:16]3([CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]3)[CH2:15][CH2:14]2)[CH:12]=[CH:11][N:10]=[CH:9]1>>[N:8]1([CH:13]2[CH2:30][CH2:29][C:16]3([CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[CH2:15][CH2:14]2)[CH:12]=[CH:11][N:10]=[CH:9]1
2
O=C(O)C(F)(F)F
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
1,331,218
[Na+]
[OH-]
null
null
ord_dataset-cfad8b3f00044bcda60a96b019f09872
2013-01-01T00:08:00
true
Aqueous sodium hydroxide (4 mL, 10%) was added to the solution of 5-benzoyl-2-p-tolylisothiazol-3-one 29 (203 mg, 0.678 mmol) in benzene (9 mL), and the mixture was stirred for 3 d at room temperature. The reaction mixture was added water (20 mL) and extracted with ethyl acetate. The combined organic layer was dried (MgSO4), filtered and evaporated. The residue was purified by flash silica gel column chromatography (hexane:ethyl acetate=2:1 to 1:1) and gave the compound 30 (77 mg, 59%). 1H-1-NMR (CDCl3, 300 MHz) δ 2.38 (s, 3H), 6.32 (d, J=6.6 Hz, 1H), 7.25 (d, J=8.1 Hz, 2H), 7.44 (d, J=8.1 Hz, 2H), 8.14 (d, J=6.6 Hz, 1H). HRMS: calculated for C10H10NOS (M+H)+192.0483. Found 192.0494.
Cc1ccc(-n2sccc2=O)cc1
null
Cc1ccc(-n2sc(C(=O)c3ccccc3)cc2=O)cc1
null
null
[OH-].[Na+].C([C:11]1[S:15][N:14]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[C:13](=[O:23])[CH:12]=1)(=O)C1C=CC=CC=1.O>C1C=CC=CC=1>[C:19]1([CH3:22])[CH:18]=[CH:17][C:16]([N:14]2[C:13](=[O:23])[CH:12]=[CH:11][S:15]2)=[CH:21][CH:20]=1
72
c1ccccc1
O
null
25
null
59.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,264,667
[Li]CCCC
null
null
null
ord_dataset-d3580a12b15e46cc91aa73f4f1a4a8cc
2013-01-01T00:03:00
true
In a dry 50 ml flask 2.47 g (10.3 mmole) 2-chloro-5-iodo-pyridine was dissolved in 20 ml of dry diethyl ether. The flask was placed under N2-atmosphere, cooled to −78° C. and 5.1 ml of a 2M solution (10.3 mmole) butyl lithium (BuLi) was added. The reaction mixture was stirred for one hour at −78° C. before adding 1 g (4.1 mmole) of the nitrile compound of example 7. Stirring was continued for 30 minutes at −78° C. and the reaction mixture was then allowed to slowly warm up to room temperature. After 16 hours at room temperature methanol was added in order to neutralise the excess BuLi, and the volatile components were evaporated. The reaction mixture was redissolved in 25 ml of a 1:1 mixture of methanol and 0.5M HCl. 0.5 g of silica gel was added and the mixture was stirred for 15 hours at room temperature. The pH was adjusted to approximately 8 by adding a concentrated NaHCO3 solution. The resulting reaction product was extracted three times by means of dichloromethane and the combined organic phases were dried over MgSO4. After filtration of the solids and evaporation of the volatile components, purification was performed by means of column chromatography, and any remaining 2-chloropyridine was removed by sublimation under high vacuum conditions. 7-(4-methoxybenzyl)-7-azabicyclo[2.2.1]hept-1-yl)-(6-chloro-pyridin-3-yl)-methanone was obtained in a 62% yield and characterised by proton (1H-NMR) and carbon (13C-NMR) nuclear magnetic resonance, infrared (IR) spectrophotometry and mass spectrum (MSES) as follows:
O=Cc1ccc(Cl)nc1
null
CO
Clc1ccc(I)cn1
null
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][N:3]=1.C([Li])CCC.[CH3:14][OH:15]>C(OCC)C>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([CH:14]=[O:15])=[CH:6][CH:7]=1
1
CCOCC
null
null
-78
62
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
46,220
null
null
null
null
ord_dataset-becaf7dc22c44672b22e4b94335cbf08
1978-01-01T00:09:00
true
To 23 parts of 1,4-dioxa-8-azaspiro[4.5]decane in 300 parts by volume of methanol is added 15 parts of ethylene oxide in methanol. The mixture is stirred at -20° C. for 3 hours and allowed to warm to room temperature. The solvent is removed under reduced pressure and the residue distilled to afford N-hydroxyethyl-1,4-dioxa-8-azaspiro[4.5]-decane. The corresponding tosylate is formed by reacting 16 parts of the alcohol in 75 parts of dry pyridine with 21 parts of p-toluenesulfonylchloride. The mixture is stirred at 5° C. overnight and then poured into 300 parts by volume of ice water. The resulting solid is collected by filtration to afford the tosylate.
OCCN1CCC2(CC1)OCCO2
null
C1CO1
C1CC2(CCN1)OCCO2
null
[O:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[CH2:11]1[O:13][CH2:12]1>CO>[OH:13][CH2:12][CH2:11][N:8]1[CH2:9][CH2:10][C:5]2([O:4][CH2:3][CH2:2][O:1]2)[CH2:6][CH2:7]1
3
CO
null
null
-20
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,080,305
null
null
null
null
ord_dataset-afd812677c134591a99f46ce28de2524
2011-01-01T00:08:00
true
10 mL of trifluoroacetic acid was added to the obtained tert-butyl 2-(2-acetoxybenzamido)-4-phenylbenzoate, and stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure and 0.50 mL of methanol, 0.50 mL of tetrahydrofuran and 6.1 mg of potassium carbonate were added to the obtained residue sequentially and stirred at room temperature for 2 hours. 10% citric acid aqueous solution was added to the reaction mixture and a solid substance was separated by filtration to obtain 8.2 mg of 2-(2-hydroxybenzamido)-4-phenylbenzoic acid as white solid.
O=C(Nc1cc(-c2ccccc2)ccc1C(=O)O)c1ccccc1O
null
CC(=O)Oc1ccccc1C(=O)Nc1cc(-c2ccccc2)ccc1C(=O)OC(C)(C)C
null
null
C([O:4][C:5]1[CH:32]=[CH:31][CH:30]=[CH:29][C:6]=1[C:7]([NH:9][C:10]1[CH:22]=[C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:20]=[CH:19][C:11]=1[C:12]([O:14]C(C)(C)C)=[O:13])=[O:8])(=O)C>FC(F)(F)C(O)=O>[OH:4][C:5]1[CH:32]=[CH:31][CH:30]=[CH:29][C:6]=1[C:7]([NH:9][C:10]1[CH:22]=[C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:20]=[CH:19][C:11]=1[C:12]([OH:14])=[O:13])=[O:8]
2
O=C(O)C(F)(F)F
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
865,070
null
null
null
null
ord_dataset-b8b98725045d45bdbd73512048f4b47e
2009-01-01T00:02:00
true
Reaction of N-butylethylenediamine (10.7 g, 0.092 mol) with cyanogen bromide (9.76 g, 0.092 mol) as described in the preparation of intermediate 6 gave 11.77 g (57% yield) of the title compound as white crystals (ether-hexane). 1HNMR 400 MHz (CDCl3) δ (ppm): 0.96 (3H, t, J=7.2 Hz, CH3), 1.41 (2H, m, CH2), 1.60 (2H, m, CH2), 3.52 (2H, t, J=7.3 Hz, CH2), 3.64-3.74 (4H, m, 2×CH2), 7.58 and 7.7 (broad s, NH). MS (ESI+) m/e 142 [M+H+].
Br
CCCCN1CCN=C1N
N#CBr
CCCCNCCN
null
[CH2:1]([NH:5][CH2:6][CH2:7][NH2:8])[CH2:2][CH2:3][CH3:4].[N:9]#[C:10][Br:11]>>[BrH:11].[CH2:1]([N:5]1[CH2:6][CH2:7][N:8]=[C:10]1[NH2:9])[CH2:2][CH2:3][CH3:4]
null
null
null
null
null
null
57.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,676,180
Cl
null
null
null
ord_dataset-9cc455db05a444779921f786a45b21a6
2015-01-01T00:12:00
true
Following general procedure B2, 4-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine hydrochloride (0.102 g, 0.34 mmol) was reacted with 2-(4-aminocyclohexyl)ethanol (0.140 g, 1.0 mmol), followed by formation of the hydrochloride salt to afford the title compound (0.006 g, 4%) as a white solid. MW=407.38. 1H NMR (DMSO-d6, 500 MHz) δ 13.48 (s, 1H), 7.97 (s, 1H), 7.84 (d, J=8.0 Hz, 1H), 7.71-7.51 (m, 3H), 7.09 (s, 1H), 4.34 (br s, 1H), 3.85-3.82 (m, 1H), 3.45 (t, J=6.0 Hz, 2H), 3.06 (t, J=7.5 Hz, 2H), 2.78 (t, J=7.5 Hz, 2H), 2.17 (quin, J=7.5 Hz, 2H), 1.91-1.85 (m, 2H), 1.78-1.73 (m, 2H), 1.46-1.32 (m, 5H), 1.16-1.05 (m, 2H); APCI MS m/z 371 [M+H]+.
OCC[C@H]1CC[C@H](Nc2cc(-c3cccc(Cl)c3)nc3c2CCC3)CC1
null
NC1CCC(CCO)CC1
Clc1cccc(-c2cc(Cl)c3c(n2)CCC3)c1
null
Cl.[Cl:2][C:3]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)[N:6]=[C:5]2[CH2:16][CH2:17][CH2:18][C:4]=12.[NH2:19][CH:20]1[CH2:25][CH2:24][CH:23]([CH2:26][CH2:27][OH:28])[CH2:22][CH2:21]1>>[ClH:2].[Cl:15][C:11]1[CH:10]=[C:9]([C:7]2[N:6]=[C:5]3[CH2:16][CH2:17][CH2:18][C:4]3=[C:3]([NH:19][C@H:20]3[CH2:25][CH2:24][C@H:23]([CH2:26][CH2:27][OH:28])[CH2:22][CH2:21]3)[CH:8]=2)[CH:14]=[CH:13][CH:12]=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
1,769,563
[Cu]I
null
null
null
ord_dataset-0b32b90cc77b4a3db47ad263e0bbc1a8
2016-01-01T00:09:00
true
To a solution of 7-bromochroman-4-one (2.0 g, 8.8 mmol) in DMF (10 mL) was added CuI (380 mg, 1.7 mmol), Pd(PPh3)Cl2 (540 mg, 0.8 mmol) and triethylamine (5 mL) under nitrogen at rt. The suspension was warmed to 100° C. and then cyclopropylacetylene (1.1 g, 17.6 mmol) was added dropwise. The mixture was stirred at 100° C. under nitrogen for 2 h. The reaction mixture was cooled to rt, poured into water, and extracted with EtOAc. Organics were separated and washed with brine, dried (Na2SO4), and concentrated. The residue was purified by silica gel chromatography to give 1.65 g (88%) of the title compound as a tan solid. 1H NMR (300 MHz, CDCl3): δ 0.83-0.93 (4H, m), 1.44-1.49 (1H, m), 2.79 (2H, t, J=6.6 Hz), 4.52 (2H, t, J=6.6 Hz), 6.96-7.00 (2H, m), 7.79 (1H, d, J=7.8 Hz). [M+H] calc'd for C14H12O, 213; found 213.
O=C1CCOc2cc(C#CC3CC3)ccc21
null
O=C1CCOc2cc(Br)ccc21
C#CC1CC1
null
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:12])[CH2:7][CH2:8][O:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH:20]1([C:23]#[CH:24])[CH2:22][CH2:21]1.O>CN(C=O)C.[Cu]I>[CH:20]1([C:23]#[C:24][C:2]2[CH:3]=[CH:4][C:5]3[C:6](=[O:12])[CH2:7][CH2:8][O:9][C:10]=3[CH:11]=2)[CH2:22][CH2:21]1
2
CN(C)C=O
O
CCN(CC)CC
100
null
88.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,233,850
null
null
null
null
ord_dataset-e96f5a2842f14e5380461c234100f05a
2012-01-01T00:12:00
true
Trifluoroacetic acid 10 mL was added to the obtained tert-butyl 2-((3-hydroxyphenyl)amino)-4-(indolin-1-yl)benzoate, and it was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the obtained residue was refined by reversed-phase silica gel column chromatography [eluent; 50-90% acetonitrile/0.1% trifluoroacetic acid aqueous solution] to give 2-((3-hydroxyphenyl)amino)-4-(indolin-1-yl)benzoic acid 13 mg of a white solid.
O=C(O)c1ccc(N2CCc3ccccc32)cc1Nc1cccc(O)c1
null
CC(C)(C)OC(=O)c1ccc(N2CCc3ccccc32)cc1Nc1cccc(O)c1
null
null
[OH:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:21]=[C:20]([N:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:24][CH2:23]3)[CH:19]=[CH:18][C:10]=2[C:11]([O:13]C(C)(C)C)=[O:12])[CH:5]=[CH:6][CH:7]=1>FC(F)(F)C(O)=O>[OH:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:21]=[C:20]([N:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH2:24][CH2:23]3)[CH:19]=[CH:18][C:10]=2[C:11]([OH:13])=[O:12])[CH:5]=[CH:6][CH:7]=1
2
O=C(O)C(F)(F)F
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
61,835
null
null
null
null
ord_dataset-d9fb402fe3e745c1893a29161cc5dda2
1980-01-01T00:01:00
true
Water, 250 ml, was added to a solution of 50 g (0.203 mole) of 2-amino-5-chlorobenzophenone oxime (mixture of isomers) in 1 l. of ether, and the mixture was stirred rapidly and cooled to 5°. Solutions of (A) 100 ml of 10% sodium hydroxide in water and (B) 33.5 g (0.228 mole) of chlorofluoroacetyl chloride made up to 100 ml with ether were simultaneously added at the same rate over 30 min., keeping the temperature of the reaction mixture at about 10° with cooling. The reaction mixture was stirred for 30 min. after the addition, and the ether layer was separated, washed with water, dried (MgSO4), and evaporated to dryness under reduced pressure. The residue was recrystallized from benzene to give 61.2 g (88%) of 2-(chlorofluoroacetamido)-5-chlorobenzophenone oxime (mixture of isomers) as light yellow crystals, mp 110°-129°. The 19F nmr (acetone-d6) indicates a mixture of two isomers in a 70:30 ratio: δ -143.2 ppm (d, d, J=50, 2.5 Hz, 30%) and δ -144.3 ppm (d, d, J=50, 2.5 Hz, 70%).
O=C(Nc1ccc(Cl)cc1C(=NO)c1ccccc1)C(F)Cl
null
Nc1ccc(Cl)cc1C(=NO)c1ccccc1
O=C(Cl)C(F)Cl
null
[NH2:1][C:2]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:3]=1[C:4](=[N:11][OH:12])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.CCOCC.[Cl:23][CH:24]([F:28])[C:25](Cl)=[O:26]>O>[Cl:23][CH:24]([F:28])[C:25]([NH:1][C:2]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:3]=1[C:4](=[N:11][OH:12])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:26]
0.5
O
CCOCC
null
null
88
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,747,280
[Cl-]
[Li]CCCC
[NH4+]
null
ord_dataset-60a3e71da3174666a50a61dcfa611a9f
2016-01-01T00:07:00
true
To a solution of 2,5-dibromopyridine (16 g, 67 mmol) in toluene (150 mL) was added 2.5 N solution of n-BuLi (27 mL, 67 mmol) dropwise at −78° C. The resulting solution was stirred at −78° C. for 1 hour before the addition of 2,2-difluoroacetate (10 g, 80 mmol). After stirred at ambient temperature overnight, the reaction solution was diluted with saturated aqueous NH4Cl solution (80 mL) at 0° C., and then extracted with ethyl acetate (2×100 mL). All the organic solution was dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by flash column chromatography with 5-10% ethyl acetate in hexane to afford the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.82 (s, 1H), 8.08 (d, J=6.0 Hz, 1H), 8.03 (d, J=6.0 Hz, 1H), 7.05 (t, J=54.4 Hz, 1H).
O=C(c1ccc(Br)cn1)C(F)F
null
O=C([O-])C(F)F
Brc1ccc(Br)nc1
null
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[Li]CCCC.[F:14][CH:15]([F:19])[C:16]([O-])=[O:17]>C1(C)C=CC=CC=1.[NH4+].[Cl-]>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:16](=[O:17])[CH:15]([F:19])[F:14])=[N:3][CH:4]=1
8
Cc1ccccc1
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
1,548,620
null
null
null
null
ord_dataset-cac8df8aff894288876df4e093c9877f
2015-01-01T00:02:00
true
Following general N—C coupling procedure 1, (R)-3-(6-amino-pyridin-3-yl)-2-oxo-1-oxa-3,7-diaza-spiro[4.5]decane-7-carboxylic acid tert-butyl ester was combined with 2-Chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide which gave (R)-3-[6-(7-Cyclopentyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-2-oxo-1-oxa-3,7-diaza-spiro[4.5]decane-7-carboxylic acid tert-butyl ester as a white solid (0.175 g, 0.275 mmol) in 64% yield. 1H NMR (400 MHz, CDCl3) δ ppm 1.47 (s, 9H) 1.55-1.68 (m, 2H) 1.68-1.85 (m, 3H) 1.88-2.18 (m, 8H) 2.50-2.68 (m, 2H) 3.13-3.21 (m, 6H) 3.21-3.32 (m, 1H) 3.37-3.58 (m, 1H) 3.61-3.72 (m, 1H) 3.75 (d, J=8.53 Hz, 2H) 3.86 (d, J=8.53 Hz, 2H) 4.72-4.95 (m, J=8.91, 8.91, 8.78, 8.53 Hz, 1H) 6.48 (s, 1H) 8.14 (dd, J=9.29, 2.76 Hz, 1H) 8.31 (br. s., 1H) 8.53 (d, J=9.54 Hz, 1H) 8.76 (s, 1H). MS m/z 605.5 (M+H)+.
CN(C)C(=O)c1cc2cnc(Nc3ccc(N4C[C@]5(CCCN(C(=O)OC(C)(C)C)C5)OC4=O)cn3)nc2n1C1CCCC1
null
CC(C)(C)OC(=O)N1CCC[C@@]2(C1)CN(c1ccc(N)nc1)C(=O)O2
CN(C)C(=O)c1cc2cnc(Cl)nc2n1C1CCCC1
null
[C:1]([O:5][C:6]([N:8]1[CH2:25][CH2:24][CH2:23][C@@:10]2([O:14][C:13](=[O:15])[N:12]([C:16]3[CH:17]=[N:18][C:19]([NH2:22])=[CH:20][CH:21]=3)[CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:26][N:27]([CH3:45])[C:28]([C:30]1[N:39]([CH:40]2[CH2:44][CH2:43][CH2:42][CH2:41]2)[C:33]2[N:34]=[C:35](Cl)[N:36]=[CH:37][C:32]=2[CH:31]=1)=[O:29]>>[C:1]([O:5][C:6]([N:8]1[CH2:25][CH2:24][CH2:23][C@@:10]2([O:14][C:13](=[O:15])[N:12]([C:16]3[CH:17]=[N:18][C:19]([NH:22][C:35]4[N:36]=[CH:37][C:32]5[CH:31]=[C:30]([C:28](=[O:29])[N:27]([CH3:26])[CH3:45])[N:39]([CH:40]6[CH2:44][CH2:43][CH2:42][CH2:41]6)[C:33]=5[N:34]=4)=[CH:20][CH:21]=3)[CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
null
null
null
null
null
null
64
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,220,196
[K+]
[Li]CCCC
[OH-]
null
ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777
2012-01-01T00:10:00
true
In a three-neck flask under a protective gas atmosphere, 1,1,3-tris(methylthio)propane (2) (3.65 g, 20 mmol) was dissolved in 50 ml of abs. THF. Subsequently, at −20° C., a butyllithium solution in n-hexane (14 ml, 1.6 M) was slowly added dropwise with stirring. In the course of this, the solution turned bright yellow. After stirring had been continued at this temperature for 2 h, gaseous dry CO2 was passed through via a frit at −70° C. over a period of 30 minutes. The reaction solution was thawed slowly until a temperature of 20° C. was attained, at which a 10% aqueous KOH solution (80 ml) was added. After phase separation, the organic phase was washed with 10% aqueous KOH solution (2×50 ml). The combined KOH phases were washed with diethyl ether (3×30 ml) and then adjusted cautiously to pH 1 with conc. HCl while cooling. The product was extracted with diethyl ether (3×50 ml). The combined ether phases were subsequently dried over Na2SO4 and, after filtration, concentrated on a rotary evaporator. 2,2,4-tris(methylthio)butanoic acid (4) was obtained as a yellowish oil (4.1 g, yield=90%), which crystallized slowly when left to stand. The NMR characterization gave the same data as in Example 3.
CSCCC(SC)(SC)C(=O)O
null
CSCCC(SC)SC
O=C=O
null
[CH3:1][S:2][CH:3]([S:8][CH3:9])[CH2:4][CH2:5][S:6][CH3:7].C([Li])CCC.[C:15](=[O:17])=[O:16].[OH-].[K+]>CCCCCC.C1COCC1>[CH3:1][S:2][C:3]([S:8][CH3:9])([CH2:4][CH2:5][S:6][CH3:7])[C:15]([OH:17])=[O:16]
2
CCCCCC
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
460,012
null
null
null
null
ord_dataset-aa5bc55d09b7465ab353e144a7ac3ad1
2000-01-01T00:03:00
true
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU--1.46 ml, 9.5 mmol) was added to a mixture of ethyl 3-chloro-6-(3-pyridylmethoxy)benzo[b]thiophene-2-carboxylate (Preparation 4, 3.0 g, 8.6 mmol) and thiophenol (1.76 ml, 17.2 mmol) in dimethylformamide (15 ml) under a nitrogen atmosphere. The solution was heated to 60° C. for 5 hours and then partitioned between diethyl ether and water. The organics were separated and washed with water, dried (magnesium sulfate) and evaporated under reduced pressure. The residue was flash chromatographed on silica gel using diethyl ether, and then ethyl acetate, as eluant. The isolated product was crystallised from diethyl ether and hexane to give the title compound as a colourless solid (2.85 g).
CCOC(=O)c1sc2cc(OCc3cccnc3)ccc2c1Sc1ccccc1
null
Sc1ccccc1
CCOC(=O)c1sc2cc(OCc3cccnc3)ccc2c1Cl
null
N12CCCN=C1CCCCC2.Cl[C:13]1[C:14]2[CH:26]=[CH:25][C:24]([O:27][CH2:28][C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)=[CH:23][C:15]=2[S:16][C:17]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19].[C:35]1([SH:41])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>CN(C)C=O>[C:35]1([S:41][C:13]2[C:14]3[CH:26]=[CH:25][C:24]([O:27][CH2:28][C:29]4[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=4)=[CH:23][C:15]=3[S:16][C:17]=2[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
null
C1CCC2=NCCCN2CC1
CN(C)C=O
null
60
null
78.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,507,072
O=C([O-])O
[Na+]
null
null
ord_dataset-1a1aa5d1c3224edca0aec6e3398da985
2014-01-01T00:11:00
true
To a stirred solution of 4-chlorobenzoyl chloride (1.0 g, 5.8 mmol) and 1-chloro-3-methoxybenzene(823.7 mmol) in CH2Cl2 (150 mL) at 0° C. was added AlCl3 (841.5 mg, 6.4 mmol). The reaction mixture was warmed to room temperature. After 12h the reaction mixture was poured into aq. NaHCO3 and extracted with CH2Cl2 (twice). The combined extracts were washed with brine, dried over Na2SO4, and concentrated in vaccuo to provide the crude product. Purification by silica gel chromatography provided (2-chloro-4-methoxyphenyl)(4-chlorophenyl)methanone(1.1 g, 4.1 mmol). (2-Chloro-4-methoxyphenyl)(4-chlorophenyl)methanone was dissolved in AcOH (60 mL) and 49% HBr (60 mL) was added. After 12h at 90° C. all volatiles were evaporated in vaccuo to afford (4-chlorophenyl)(2,4-dihydroxyphenyl)methanone in quantitative yield. This was dissolved in MeOH (30 mL) and THF (6 mL) and cooled to 0° C. Into the reaction mixture NaBH4 (235.5 mg, 6.2 mmol) was added. After 30 minutes the reaction was quenched with aq. NH4Cl and extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, and concentrated in vaccuo. Without purification this was subjected to alkylation with 1,8-dibromoocatane (3.3 g, 12.3 mmol) and K2CO3 (1.7 g, 12.3 mmol) in DMF (45 mL). After 12h the reaction mixture was diluted with water (150 mL) and water phase was extracted with EtOAc (twice). The combined organic phase was washed with brine, dried over Na2SO4, and concentrated in vaccuo to give the crude product. Purification by silica gel chromatography provided (4-(8-bromooctyloxy)-2-chlorophenyl)(4-chlorophenyl)methanol (1.6 g, 3.5 mmol). To a stirred solution of (4-(8-bromooctyloxy)-2-chlorophenyl)(4-chlorophenyl)methanol (1.6 g, 3.5 mmol) in THF (25 mL) was added N-methylprop-2-en-1-amine (746 mg, 10.5 mmol) and NaHCO3 (11.0 mmol). After 36h at room temperature the reaction mixture was filtered through a glass-filter. The filtrate was evaporated in vaccuo. Purification by silica gel chromatography provided (4-(8-(allyl(methyl)amino)octyloxy)-2-chlorophenyl)(4-chlorophenyl)methanol (1.5 g, 3.3 mmol); 1H-NMR (300 MHz, CDCl3); 7.29-7.17 ppm (m, 5H), 6.84 (d, J=10.1 Hz, 1H), 6.74 (s, 1H), 5.98-5.80 (m, 2H), 5.31-5.15 (m, 2H), 3.85 (t, J=7.6 Hz, 2H), 3.20-3.08 (m, 2H), 2.58-2.40 (m, 2H), 2.35 (s, 3H), 1.77-1.45 (m, 4H), 1.32-1.15 (m, 8H); 13C—NMR (75 MHz, CDCl3) 156.3 ppm, 138.3, 134.2, 131.8, 130.0, 129.6, 129.3, 116.2, 74.5, 68.8, 60.4, 43.8, 57.0, 29.6, 29.3, 28.1, 27.3, 25.9; ESI-MS calcd for C25H34Cl2NO2 [M+H]+: 450.2. found 450.2.
C=CCN(C)CCCCCCCCOc1ccc(C(O)c2ccc(Cl)cc2)c(Cl)c1
null
OC(c1ccc(Cl)cc1)c1ccc(OCCCCCCCCBr)cc1Cl
C=CCNC
null
Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[OH:18])=[C:13]([Cl:26])[CH:12]=1.[CH3:27][NH:28][CH2:29][CH:30]=[CH2:31].C([O-])(O)=O.[Na+]>C1COCC1>[CH2:29]([N:28]([CH3:27])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[OH:18])=[C:13]([Cl:26])[CH:12]=1)[CH:30]=[CH2:31]
null
C1CCOC1
null
null
null
94.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,230,070
null
null
null
null
ord_dataset-cde802cdb7434a5f82a22981ccaefc4e
2012-01-01T00:11:00
true
Compound 27 (3.5 g, 8.29 mmol) was dissolved in bromobenzene (150 mL). The solution was heated at 140° C. under N2 and monitored by LC every hour. The reaction was complete after 7 hours. The solution was evaporated and purified by flash chromatography (3% MeOH/CH2Cl2) to give 2.5 g (83%) of intended product as a tan solid. 1H NMR (400 MHz, CDCl3): δ 8.22 (s, 1H), 7.27-7.39 (m, 6H), 5.40 (s, 2H), 2.57 (s, 3H). MS (ES) [m+H] calc'd for C21H23N3OSi, 362; found 362.
Cc1cnc2[nH]c3c(=O)n(Cc4ccccc4)cc([Si](C)(C)C)c3c2c1
null
Cc1cnc(Nc2nc(Cl)cn(Cc3ccccc3)c2=O)c(C#C[Si](C)(C)C)c1
null
null
[CH2:1]([N:8]1[CH:13]=C(Cl)N=[C:10]([NH:15][C:16]2[C:21]([C:22]#[C:23][Si:24]([CH3:27])([CH3:26])[CH3:25])=[CH:20][C:19]([CH3:28])=[CH:18][N:17]=2)[C:9]1=[O:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>BrC1C=CC=CC=1>[CH2:1]([N:8]1[CH:13]=[C:23]([Si:24]([CH3:26])([CH3:25])[CH3:27])[C:22]2[C:21]3[CH:20]=[C:19]([CH3:28])[CH:18]=[N:17][C:16]=3[NH:15][C:10]=2[C:9]1=[O:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
7
Brc1ccccc1
null
null
140
null
83.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,645,225
[K+]
null
null
null
ord_dataset-bcc0b01d4f58457a8733b10a099f43ba
2015-01-01T00:10:00
true
2-amino-4-methylbenzonitrile (10 g, 75.7 mmol) was dissolved in ethanol, added with potassium hydroxide (21.2 g, 378 mmol), followed by refluxing for 8 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and dissolved in ethyl acetate. The organic layer formed was washed with a saturated aqueous solution of sodium bicarbonate and brine. The obtained organic layer is dried over anhydrous sodium sulfate, concentrated under reduced pressure, and recrystallized from ethanol to obtain the title compound (4.9 g, 43%).
Cc1ccc(C(N)=O)c(N)c1
null
Cc1ccc(C#N)c(N)c1
[OH-]
null
[NH2:1][C:2]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[OH-:11].[K+]>C(O)C>[NH2:1][C:2]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:3]=1[C:4]([NH2:5])=[O:11]
null
CCO
null
null
25
43.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
53,811
null
null
null
null
ord_dataset-053897d9b1744303b2fdfe3e796ca27b
1979-01-01T00:04:00
true
A solution of 1-methoxy-4-(1-hydroxy-1-methylethyl)-1,4-cyclohexadiene in dichloromethane containing 5-(1,2-dimethyl-1-heptenyl)resorcinol was stirred at 0° C. while stannic chloride was added in one portion. The reaction mixture was then stirred for four hours at 24° C., and then washed with hydrochloric acid and water. The solution was dried and the solvent was removed by evaporation under reduced pressure to provide dl-cis-1-hydroxy-3-(1,2-dimethyl-1-heptenyl)-6,6-dimethyl-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-one.
CCCCCC(C)=C(C)c1cc(O)c2c(c1)OC(C)(C)[C@@H]1CCC(=O)C[C@H]21
null
CCCCCC(C)=C(C)c1cc(O)cc(O)c1
COC1=CCC(C(C)(C)O)=CC1
null
C[O:2][C:3]1[CH2:8][CH:7]=[C:6]([C:9]([OH:12])([CH3:11])[CH3:10])[CH2:5][CH:4]=1.[CH3:13][C:14]([C:22]1[CH:23]=[C:24](O)[CH:25]=[C:26]([CH:28]=1)[OH:27])=[C:15]([CH3:21])[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]>ClCCl>[OH:27][C:26]1[C:25]2[C@H:5]3[CH2:4][C:3](=[O:2])[CH2:8][CH2:7][C@H:6]3[C:9]([CH3:11])([CH3:10])[O:12][C:24]=2[CH:23]=[C:22]([C:14]([CH3:13])=[C:15]([CH3:21])[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH:28]=1
4
ClCCl
null
null
24
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
22,414
null
null
null
null
ord_dataset-19b9e29d593f4660ab77c07b459da9bb
1977-01-01T00:04:00
true
Adipic acid (36.5g, 0.25 mole) and the catalyst of Example II (0.4g) in methyl isobutyl ketone (250 ml) were heated at 160° C and subsequently ethylene oxide (24.23g, 0.55 mole) was added; the temperature was kept at 160° C. After 60 minutes, the pressure dropped from 103 psi to 57 psi. After solvent evaporation, the crude product (60.4g) was distilled under vacuum; a light yellow material (35.0g) was obtained boiling at 202°-203° C at 1 mm pressure in 60.0% yield, having a refractive index of 1.4619 at 25° C. The infrared spectrum was consistent with that expected for the ester (3450 cm-1 (OH), 2970 cm-1 (CH2), 1730 cm-1 (C=O), and 1180 cm-1 (C-O)). Anal. Calcd. for C10H18O6 : C, 51.28; H, 7.69; O, 41.03, Found: C, 50.80; H, 7.76; Molecular weight by hydroxy number: Theory: 234. Found: 234.
O=C(CCCCC(=O)OCCO)OCCO
null
O=C(O)CCCCC(=O)O
CC(=O)CC(C)C
C1CO1
[C:1]([OH:10])(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([OH:8])=[O:7].[CH2:11]1[O:13][CH2:12]1.[CH2:14]([C:18](C)=[O:19])C(C)C>>[OH:19][CH2:18][CH2:14][O:7][C:6](=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2][C:1]([O:10][CH2:12][CH2:11][OH:13])=[O:9]
1
null
null
null
null
60
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
356,957
Cl
null
null
null
ord_dataset-58ec5adfcd8648dc9e26ee757d289517
1997-01-01T00:03:00
true
1 g of methyl (4-{4-[4-(aminoiminomethyl)phenyl]-1,3-thiazol-2-ylamino}piperid-1-yl)acetate hydrochloride (EXAMPLE 1) is added to 20 ml of 6N hydrochloric acid and the reaction mixture is heated under reflux for 5 hours. The mixture is evaporated to dryness and the residue is crystallized from acetone to give white crystals which melt at 216° C.; yield: 96%.
NN=Cc1ccc(-c2csc(NC3CCN(CC(=O)O)CC3)n2)cc1
null
COC(=O)CN1CCC(Nc2nc(-c3ccc(C=NN)cc3)cs2)CC1
null
null
[ClH:1].[NH2:2][N:3]=[CH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([NH:16][CH:17]3[CH2:22][CH2:21][N:20]([CH2:23][C:24]([O:26]C)=[O:25])[CH2:19][CH2:18]3)[S:14][CH:15]=2)=[CH:7][CH:6]=1>Cl>[ClH:1].[ClH:1].[ClH:1].[NH2:2][N:3]=[CH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([NH:16][CH:17]3[CH2:18][CH2:19][N:20]([CH2:23][C:24]([OH:26])=[O:25])[CH2:21][CH2:22]3)[S:14][CH:15]=2)=[CH:7][CH:6]=1
null
null
null
null
null
96
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,244,410
null
null
null
null
ord_dataset-c544c0c663f54dbea4ddb52ddde7934e
2013-01-01T00:01:00
true
The title compound was prepared from 7-cyclopropyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.29) (174 mg, 0.5 mmol) and N-hydroxy-3-sulfamoyl-benzamidine [CAS-No. 9000-88-7] (161 mg, 0.75 mmol) according to general procedure II. Obtained after purification by column chromatography (dichloromethane/MeOH/NH4OH) and crystallization (ethyl acetate/MeOH/hexane) as an off-white solid (142 mg, 54%). MS (EI) 526.1 [(M)+]; mp 277° C.
NS(=O)(=O)c1cccc(-c2noc(-c3cnn4c(C5CC5)cc(-c5ccc(C(F)(F)F)cc5)nc34)n2)c1
null
O=C(O)c1cnn2c(C3CC3)cc(-c3ccc(C(F)(F)F)cc3)nc12
N=C(NO)c1cccc(S(N)(=O)=O)c1
null
[CH:1]1([C:4]2[N:9]3[N:10]=[CH:11][C:12]([C:13]([OH:15])=O)=[C:8]3[N:7]=[C:6]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[CH:5]=2)[CH2:3][CH2:2]1.O[NH:27][C:28](=[NH:39])[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([S:35](=[O:38])(=[O:37])[NH2:36])[CH:30]=1>>[CH:1]1([C:4]2[N:9]3[N:10]=[CH:11][C:12]([C:13]4[O:15][N:39]=[C:28]([C:29]5[CH:30]=[C:31]([S:35]([NH2:36])(=[O:37])=[O:38])[CH:32]=[CH:33][CH:34]=5)[N:27]=4)=[C:8]3[N:7]=[C:6]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[CH:5]=2)[CH2:2][CH2:3]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
805,867
null
null
null
null
ord_dataset-ed846b4b229e4bb09ad9dba95ad7ebeb
2008-01-01T00:01:00
true
Amine 3 (90.0 g, ˜0.41 mol) was dissolved in methylene chloride (810 ml). Triethylamine (66.6 g, 0.66 mol) was added and the solution was cooled to 5° C. Methyl chloroformate (47.0 g, 0.50 mol) in methylene chloride (100 ml) was then added slowly and the reaction temperature was maintained between 10° C. and 14° C. After addition was complete, the reaction solution was stirred at room temperature for 12 hours. Water (540 ml) was added. Aqueous phase was separated. Organic phase was concentrated to dryness to afford crude compound 4. The crude product was used in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 0.279 (s, 9H), 2.86 (d, br, 3H), 3.774 (s, 3H), 4.484 (s, br, 2H), 7.190 (s, br, 2H), 7.46 (d, 2H, J=8.10 Hz).
COC(=O)N(C)Cc1ccc(C#C[Si](C)(C)C)cc1
null
CNCc1ccc(C#C[Si](C)(C)C)cc1
COC(=O)Cl
null
[CH3:1][NH:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]#[C:11][Si:12]([CH3:15])([CH3:14])[CH3:13])=[CH:6][CH:5]=1.C(N(CC)CC)C.Cl[C:24]([O:26][CH3:27])=[O:25].O>C(Cl)Cl>[CH3:27][O:26][C:24](=[O:25])[N:2]([CH3:1])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]#[C:11][Si:12]([CH3:13])([CH3:15])[CH3:14])=[CH:6][CH:5]=1
12
ClCCl
CCN(CC)CC
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
227,848
null
null
null
null
ord_dataset-d98d003e9abb4b579746c5a361466e14
1991-01-01T00:05:00
true
starting from ethyl 5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate and p-(trifluoromethoxy)-benzoyl chloride, there is obtained ethyl N-[p-(trifluoromethoxy)-benzoyl]-5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate as a syrup, mass spectrum m/e: M+ 454 (1), 425 (11), 194 (100), 189 (40);
CCOC(=NC(=O)c1ccc(OC(F)(F)F)cc1)N1Cc2ccccc2-c2ccccc2C1
null
CCOC(=N)N1Cc2ccccc2-c2ccccc2C1
O=C(Cl)c1ccc(OC(F)(F)F)cc1
null
[CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([C:16](=[NH:20])[O:17][CH2:18][CH3:19])[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[F:21][C:22]([F:34])([F:33])[O:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][CH:25]=1>>[F:21][C:22]([F:33])([F:34])[O:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([N:20]=[C:16]([N:7]2[CH2:6][C:5]3[CH:4]=[CH:3][CH:2]=[CH:1][C:11]=3[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8]2)[O:17][CH2:18][CH3:19])=[O:29])=[CH:26][CH:25]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
840,857
null
null
null
null
ord_dataset-074f86301ec5441ab3b52d902ac06949
2008-01-01T00:09:00
true
Title compound was prepared according to the procedure described in example G from N-Boc-piperazine and 2-Chloro-5-trifluoromethylbenzonitrile (CAS: 328-87-0)(15% yield, yellow oil, MS (m/e): 373.1 (M+NH4+, 100%).
CC(C)(C)OC(=O)N1CCN(c2ccc(C(F)(F)F)cc2C#N)CC1
null
N#Cc1cc(C(F)(F)F)ccc1Cl
CC(C)(C)OC(=O)N1CCNCC1
null
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl[C:15]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][C:16]=1[C:17]#[N:18]>>[C:4]([O:3][C:1]([N:8]1[CH2:9][CH2:10][N:11]([C:15]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][C:16]=2[C:17]#[N:18])[CH2:12][CH2:13]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]
null
null
null
null
null
15
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,045,304
[H-]
[Na+]
null
null
ord_dataset-dd320ded4b3f4764af39de99491533f7
2011-01-01T00:04:00
true
A mixture of cyclobutanol (1.0 mL, 14.0 mmol) and sodium hydride (0.5 g, 14.0 mmol) in DMF (20 mL) was stirred at 0° C. for 30 minutes. 5-(Bromomethyl)benzofuran (2.9 g, 14.0 mmol) was the added and resultant reaction mixture was slowly warmed to room temperature and left stirring over night. Reaction mixture was diluted to 100 mL with water. The solution was extracted with Et2O (20 mL×3); the combined extracts were washed with 1N NaOH solution, water and brine, dried, and concentrated under reduced pressure to yield the desired product after purification on silica (4/1 hexane/ethyl acetate). 1H NMR (400 MHz, CDCl3) δ 7.58 (d, 2H), 7.42 (d, 1H), 7.27 (d, 1H), 6.78 (s, 1H), 4.54 (s, 2H) 4.03 (m, 1H), 2.21 (m, 2H), 1.94 (m, 2H), 1.76 (m, 1H), 1.52 (m, 1H).
c1cc2cc(COC3CCC3)ccc2o1
null
OC1CCC1
BrCc1ccc2occc2c1
null
[CH:1]1([OH:5])[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:9][C:10]1[CH:11]=[CH:12][C:13]2[O:17][CH:16]=[CH:15][C:14]=2[CH:18]=1>CN(C=O)C.O>[CH:1]1([O:5][CH2:9][C:10]2[CH:11]=[CH:12][C:13]3[O:17][CH:16]=[CH:15][C:14]=3[CH:18]=2)[CH2:4][CH2:3][CH2:2]1
0.5
CN(C)C=O
O
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
629,600
Cl
null
null
null
ord_dataset-0a66204fc43e49c2922e6f9107e6b62f
2004-01-01T00:03:00
true
To 304 mg (1 mmol) 6-Hydroxy-3,4-dihydro-2H-quinoline-1-carboxylic acid 4-chloro-phenyl ester in 4 ml DMF 420 mg (3 mmol) K2CO3 (powdered) and 416 mg (2 mmol) 1,4-dibromobutene were added. The mixture was stirred at 50° C. for 1 h, diluted with EtOAc and water. 2M HCl was added and the inorganic phase was extracted with EtOAc. The combined organic phases were washed with water and dried over Na2SO4. The crude product was purified by column chromatography on silica gel with hexane/EtOAc 9:1 to 4:1 to yield 250 mg (46%) 6-(4-Bromo-but-2-enyloxy)-3,4-dihydro-2H-quinoline-1-carboxylic acid 4-chloro-phenyl ester as colorless gum, MS: 436 (MH+, 1Br, 1Cl).
O=C(Oc1ccc(Cl)cc1)N1CCCc2cc(OCC=CCBr)ccc21
null
O=C(Oc1ccc(Cl)cc1)N1CCCc2cc(O)ccc21
BrC=CCCBr
null
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([N:11]2[C:20]3[C:15](=[CH:16][C:17]([OH:21])=[CH:18][CH:19]=3)[CH2:14][CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.CN(C=O)C.[Br:27][CH:28]=[CH:29][CH2:30][CH2:31]Br.Cl>CCOC(C)=O.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([N:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH2:31][CH:30]=[CH:29][CH2:28][Br:27])=[CH:18][CH:19]=3)[CH2:14][CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1
1
CN(C)C=O
CCOC(C)=O
O
50
null
57.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
238,570
Cl
[K+]
null
null
ord_dataset-960c6b9c4fc74afd90a3ebf713215626
1991-01-01T00:12:00
true
A solution of potassium cyanide (25 g) in water (133 ml) and of 4-picolyl chloride hydrochloride (30 g) in reagent grade methanol (268 ml) was heated under reflux for 2 hours, concentrated under vacuum, diluted with water (500 ml) and extracted with CHCl3 (4×100 ml). Distillation of the extract afforded a single fraction of 4-pyridylacetonitrile (8.026 g), b.p. 84° C. at 0.15 mm Hg. This was dissolved in dry dimethylformamide (130 ml) and stirred with sodium hydride (3.4 g, 50% w/v dispersion in oil) for 2.5 hours. Ethyl iodide (5.7 ml, 1.93 g/ml) was added slowly with cooling and stirring. After 18 hours, excess solvent was evaporated off, the residue diluted with water (150 ml) and extracted with diethyl ether (3×300 ml). Flash chromatography (Merck Art 9385, CHCl3, 4.5×15 cm column) of the extract afforded a mixture of 2-(4-pyridyl)butyronitrile and 2-ethyl-2-(4-pyridyl)-butyronitrile (9.85 g). Acrylonitrile (4.46 ml) in t-butanol (5.5 ml) was added to a solution of the above mixture in t-butanol (18 ml) and "Triton B" (0.32 ml) with cooling and stirring. ("Triton" is a Registered Trade Mark in the UK and many other countries). After 2 hours, excess solvent was evaporated off, the residue diluted with water (150 ml) and extracted with CHCl3 (2×50 ml). Flash chromatography of the extract (CHCl3, 4.5×15 cm column) afforded a mixture of 2-ethyl-2-(4-pyridyl) butyronitrile and 4-cyano-4-(4-pyridyl)hexanonitrile (8 g). This mixture was heated under reflux with glacial acetic acid (15 ml) and conc. sulfuric acid (3 ml) during 0.5 hours, then with addition of 5N hydrochloric acid (15 ml) for a further 3 hours, cooled, diluted with water, adjusted to pH 7-7.5 with sodium hydrogen carbonate and extracted with methylene chloride. Elution from a column (4.5×30 cm) of silica gel (Merck, Kieselgel 6) with CHCl3 afforded the title compound, 2.95 g; (20% yield based on 4-pyridylacetonitrile) which crystallized from toluene, m.p. 138°-139° C. (corrected); mass spectrum, isobutane chemical ionization [MH+ ] at m/z=219: IR (KC1) cm-1 2990 (CH aromatic phenyl), 2800 (NH), 1720, 1784 (C=0 imide), 1605 (C=C, aromatic phenyl); 1H-NMR (CDCl3), δ0.87 (t,3H,CH3CH2), 1.80-2.82 (m, 6H, CH3CH2, H(4), H(5)), 7.15 (d, 2H, aromatic H(3), H(5), J=4.7 Hz), 8.55 (d, 2H, aromatic H(2), H(6), J=4.7 Hz), 9.13 (br.s., 1H, NH). Anal. C12H14N2O2, 218.25) Calcd: C,66.03; H,6.47; N,12.84, Found: C,66.00, H,6.58; N,12.87%.
N#CCc1ccncc1
null
ClCc1ccncc1
[C-]#N
null
[C-:1]#[N:2].[K+].Cl.[N:5]1[CH:10]=[CH:9][C:8]([CH2:11]Cl)=[CH:7][CH:6]=1.CO>O>[N:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:1]#[N:2])=[CH:7][CH:6]=1
null
O
CO
null
null
37.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,040,670
O=C([O-])[O-]
[Cs+]
null
null
ord_dataset-3af92aec23dc4810b92eb0d8c60023ee
2011-01-01T00:03:00
true
(3,5-Bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-[2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-5-trifluoromethyl-benzyl]-amine (250 mg) is dissolved in 1,4-dioxane (5 ml) and thereto are added ethyl 4-chloro-2-trifluoromethyl-pyrimidine-5-carboxylate (140 mg), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (30 mg) and cesium carbonate (177 mg), and the mixture is stirred under nitrogen atmosphere at 80° C. overnight. The reaction solution is cooled to room temperature, and thereto are added water and ethyl acetate and the insoluble materials are removed by filtration through Celite™. The filtrate is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:1→4:1) to give ethyl 4-(2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-2-trifluoromethyl-pyrimidine-5-carboxylate (199 mg). MS (m/z): 783 [M+H]+
CCOC(=O)c1cnc(C(F)(F)F)nc1-c1ccc(C(F)(F)F)cc1CN(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ncc(N2CCOCC2)cn1
null
CCOC(=O)c1cnc(C(F)(F)F)nc1Cl
CC1(C)OB(c2ccc(C(F)(F)F)cc2CN(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2ncc(N3CCOCC3)cn2)OC1(C)C
null
[F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([CH:40]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:42]=1)[CH2:6][N:7]([C:28]1[N:33]=[CH:32][C:31]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[CH:30][N:29]=1)[CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1B1OC(C)(C)C(C)(C)O1.Cl[C:50]1[C:55]([C:56]([O:58][CH2:59][CH3:60])=[O:57])=[CH:54][N:53]=[C:52]([C:61]([F:64])([F:63])[F:62])[N:51]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.C(OCC)(=O)C>[F:46][C:43]([F:45])([F:44])[C:41]1[CH:40]=[C:5]([CH:4]=[C:3]([C:2]([F:48])([F:1])[F:47])[CH:42]=1)[CH2:6][N:7]([CH2:8][C:9]1[CH:14]=[C:13]([C:15]([F:17])([F:18])[F:16])[CH:12]=[CH:11][C:10]=1[C:54]1[C:55]([C:56]([O:58][CH2:59][CH3:60])=[O:57])=[CH:50][N:51]=[C:52]([C:61]([F:63])([F:64])[F:62])[N:53]=1)[C:28]1[N:29]=[CH:30][C:31]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[CH:32][N:33]=1
8
C1COCCO1
CCOC(C)=O
O
80
70.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
957,514
null
null
null
null
ord_dataset-ed65749688da45af8a8432967b017729
2010-01-01T00:05:00
true
(±)-Trans-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1yl)-4-(thiophen-3-yl)pyrrolidine-2,5-dione was prepared according to Example 40 replacing 2-chloro-4-fluorophenylacetamide with thiophen-3-ylacetamide. Yield 50.3 mg, 15.0%. 1H NMR (DMSO-d6) 400 MHz δ: 11.50 (s, 1H), 7.52 (m, 1H), 7.49 (m, 1H), 7.35 (s, 1H), 7.21 (dd, 1H, J=4.01.2 Hz), 7.16 (d, 1H, 7.6 Hz), 6.89 (d, 1H, J=4.4 Hz), 6.85 (t, 1H, J=6.8 Hz), 4.56 (d, 1H, J=7.2 Hz), 4.41 (d, 1H, J=7.2 Hz), 4.10 (t, 2H, J=6.0 Hz), 2.90 (t, 2H, J=6.0 Hz), 2.10 (m, 2H).
O=C1NC(=O)[C@@H](c2cn3c4c(cccc24)CCC3)[C@@H]1c1ccsc1
null
NC(=O)Cc1ccsc1
NC(=O)Cc1ccc(F)cc1Cl
null
Cl[C:2]1[CH:7]=[C:6](F)[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([NH2:12])=O.[S:13]1[CH:17]=[CH:16][C:15]([CH2:18][C:19]([NH2:21])=[O:20])=[CH:14]1>>[C:9]1([C@H:18]2[C@H:18]([C:15]3[CH:16]=[CH:17][S:13][CH:14]=3)[C:19](=[O:20])[NH:21][C:19]2=[O:20])[C:3]2=[C:4]3[C:5](=[CH:6][CH:7]=[CH:2]2)[CH2:16][CH2:15][CH2:14][N:12]3[CH:10]=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
1,456,925
c1c[nH]cn1
null
null
null
ord_dataset-a86112d52cd54525a5e36d41f18aced2
2014-01-01T00:07:00
true
2-[5-Bromo-2-(hydroxymethyl)phenyl]propan-2-ol (1.1 g, 4.4 mmol) and imidazole (0.78 g, 12 mmol) were dissolved in N,N-dimethylformamide (5 mL), and tert-butyldimethylchlorosilane (0.86 g, 5.7 mmol) was added, followed by stirring at room temperature overnight. Water was added to the reaction solution, followed by extraction with hexane, and subsequently the extract was washed sequentially with water and a saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. After the organic layer was concentrated under reduced pressure, the resulting residue was purified by chromatography on a silica gel column (Biotage Ltd., elution solvent: hexane/ethyl acetate) to afford the title compound (1.1 g, 3.1 mmol) as a colorless oil (yield 70%).
CC(C)(O)c1cc(Br)ccc1CO[Si](C)(C)C(C)(C)C
null
CC(C)(O)c1cc(Br)ccc1CO
CC(C)(C)[Si](C)(C)Cl
null
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:12][OH:13])=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:7]=1.N1C=CN=C1.[C:19]([Si:23]([CH3:26])([CH3:25])Cl)([CH3:22])([CH3:21])[CH3:20].O>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:12][O:13][Si:23]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:26])[CH3:25])=[C:6]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:7]=1
8
CN(C)C=O
O
null
25
null
70.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
616,001
null
null
null
null
ord_dataset-31fc6d0085ca4d8dbbcd3a5fa9dcedfb
2003-01-01T00:11:00
true
A suspension of 4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carbothioic acid amide (20 mg, 50 μmol) and KLCO3 (8.0 eq, 400 μmol) in THF (5 ml) was stirred vigorously for 5 min and ethyl bromopyruvate (29 mg, 150 μmol) was added neat via syringe. The resulting, pale yellow solution was stirred at rt for 1 h, cooled to 0° C. with the aid of an ice bath and treated sequentially with pyridine (8.0 eq, 400 μmol) and (F3CCO)2O (4.0 eq, 42 mg, 200 μmol). The resulting deep red solution was allowed to reach ambient temperature overnight. Following the addition of water (4 ml), the mixture was concentrated in vacuo and extracted with CH2Cl2 (2×10 ml). The combined organic phases were washed with 2 N HCl, dried (Na2SO4), filtered and concentrated in vacuo. The solution was purified by radial chromatography (1 mm plate) using 2-5% MeOH in CH2Cl2 as eluent to afford a white solid (22 mg, 88%). MS: 500 (MH+).
CCCn1c(=O)c2[nH]c(C34CCC(c5nc(C(=O)OCC)cs5)(CC3)CC4)nc2n(CCC)c1=O
null
CCOC(=O)C(=O)CBr
CCCn1c(=O)c2[nH]c(C34CCC(C(N)=S)(CC3)CC4)nc2n(CCC)c1=O
null
[O:1]=[C:2]1[N:10]([CH2:11][CH2:12][CH3:13])[C:9]2[N:8]=[C:7]([C:14]34[CH2:21][CH2:20][C:17]([C:22](=[S:24])[NH2:23])([CH2:18][CH2:19]3)[CH2:16][CH2:15]4)[NH:6][C:5]=2[C:4](=[O:25])[N:3]1[CH2:26][CH2:27][CH3:28].Br[CH2:30][C:31](=O)[C:32]([O:34][CH2:35][CH3:36])=[O:33].N1C=CC=CC=1.O>C1COCC1>[CH2:35]([O:34][C:32]([C:31]1[N:23]=[C:22]([C:17]23[CH2:20][CH2:21][C:14]([C:7]4[NH:6][C:5]5[C:4](=[O:25])[N:3]([CH2:26][CH2:27][CH3:28])[C:2](=[O:1])[N:10]([CH2:11][CH2:12][CH3:13])[C:9]=5[N:8]=4)([CH2:19][CH2:18]2)[CH2:15][CH2:16]3)[S:24][CH:30]=1)=[O:33])[CH3:36]
0.08
C1CCOC1
c1ccncc1
O
0
88.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,674,968
O=S(=O)(O)O
null
null
null
ord_dataset-9cc455db05a444779921f786a45b21a6
2015-01-01T00:12:00
true
A mixture of sulfuric acid (5.79 g, 59.03 mmol, 2.25 equiv) and nitric acid (2.48 g, 39.37 mmol, 1.50 equiv) was added into 1-bromo-4-tert-butylbenzene (5.6 g, 26.28 mmol, 1.00 equiv) while maintaining the temperature below 10° C. The resulting solution was stirred for 20 h at 25° C., poured into water and extracted with ether. The organic phase was dried over anhydrous sodium sulfate. After filtered and concentrated under reduced pressure, the residue was purified through a silica gel column with ethyl acetate/petroleum ether (1:200-1:50) to afford the title compound as a yellow liquid. 1H-NMR (400 MHz, DMSO-d6): δ ppm 1.361(s, 9H), 7.454(dd, J=2.4 Hz, J=8.4 Hz, 1H), 7.65(d, J=8.4 Hz, 1H), 7.848(d, J=2.4 Hz, 1H).
CC(C)(C)c1ccc(Br)c([N+](=O)[O-])c1
null
CC(C)(C)c1ccc(Br)cc1
O=[N+]([O-])O
null
S(=O)(=O)(O)O.[N+:6]([O-:9])(O)=[O:7].[Br:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][CH:12]=1>O>[Br:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][C:12]=1[N+:6]([O-:9])=[O:7]
20
O
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,145,487
CCCC[N+](CCCC)(CCCC)CCCC
[F-]
null
null
ord_dataset-68715347640045adb1b09e6a04722b0e
2012-01-01T00:03:00
true
Tetrabutylammonium fluoride (881 μl, 0.88 mmol) was added to (S)-2-(tert-butyldimethylsilyloxy)-3-((R)-2-methoxypropoxy)-N-(5-methylpyrazin-2-yl)propanamide (Intermediate Y11) (169 mg, 0.44 mmol) in THF (2203 μl) at room temperature under nitrogen. The resulting solution was stirred at room temperature for 3 hours. The reaction mixture was quenched with water (5 mL), extracted with ethyl acetate (3×10 mL), the organic layer was back washed with water (5 mL), dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0 to 100% ethyl acetate in isohexane to afford the product (64.0 mg, 53.9%). 1H NMR (400 MHz, CDCl3) δ 1.13 (d, 3H), 2.53 (s, 3H), 3.33-3.43 (m, 5H), 3.68-3.82 (m, 2H), 4.04-4.11 (m, 1H), 4.33 (t, 1H), 4.53 (s, 1H), 8.12-8.15 (m, 1H), 9.19 (s, 1H), 9.43 (d, 1H); m/z (ESI+) (M+H)+=270.24; HPLC tR=1.04 min.
CO[C@H](C)COC[C@H](O)C(=O)Nc1cnc(C)cn1
null
CO[C@H](C)COC[C@H](O[Si](C)(C)C(C)(C)C)C(=O)Nc1cnc(C)cn1
null
null
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][C@@H:27]([CH2:38][O:39][CH2:40][C@H:41]([O:43][CH3:44])[CH3:42])[C:28]([NH:30][C:31]1[CH:36]=[N:35][C:34]([CH3:37])=[CH:33][N:32]=1)=[O:29])(C(C)(C)C)(C)C>C1COCC1>[OH:26][C@@H:27]([CH2:38][O:39][CH2:40][C@H:41]([O:43][CH3:44])[CH3:42])[C:28]([NH:30][C:31]1[CH:36]=[N:35][C:34]([CH3:37])=[CH:33][N:32]=1)=[O:29]
3
C1CCOC1
null
null
25
54
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
957,103
CN(C)C(On1nnc2cccnc21)=[N+](C)C
F[P-](F)(F)(F)(F)F
null
null
ord_dataset-ed65749688da45af8a8432967b017729
2010-01-01T00:05:00
true
To a mixture of 4-amino-3-chloro-benzoic acid (Fluorochem; 2.575 g, 15 mmol) and 1-ethylpiperidin-4-amine (Fluorochem; 2.12 g, 16.5 mmol) in DMF (50 mL), was added DIPEA (5.2 mL, 30 mmol). The mixture was cooled with an ice-bath. HATU (6.27 g), added and the reaction mixture stirred at ambient temperature for 18 hours. The solvent was evaporated and the residue partitioned between saturated aqueous sodium bicarbonate solution (100 mL), and Ethyl Acetate (4×50 mL). The organic extracts were washed with brine (2×75 ml), dried over anhydrous Magnesium sulphate, filtered, and the solvent evaporated to give the crude product as a gum, which was triturated with ether to yield the title compound as a tan solid (3.54 g, 84%).
CCN1CCC(NC(=O)c2ccc(N)c(Cl)c2)CC1
null
Nc1ccc(C(=O)O)cc1Cl
CCN1CCC(N)CC1
null
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[Cl:11].[CH2:12]([N:14]1[CH2:19][CH2:18][CH:17]([NH2:20])[CH2:16][CH2:15]1)[CH3:13].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:20][CH:17]2[CH2:18][CH2:19][N:14]([CH2:12][CH3:13])[CH2:15][CH2:16]2)=[O:8])=[CH:4][C:3]=1[Cl:11]
18
CN(C)C=O
CCN(C(C)C)C(C)C
null
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
1,262,520
[Na+]
[OH-]
null
null
ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0
2013-01-01T00:02:00
true
2.9 mL (2.9 mmol) of aqueous 1 N sodium hydroxide solution are added to a solution of 0.8 g (1.9 mmol) of methyl (Z)-2-methoxy-3-[3′-(1-methyl-3-pentylureido)biphenyl-4-yl]acrylate in 15 mL of tetrahydrofuran. The reaction medium is heated at 68° C. and stirred for 4 hours. The reaction medium is acidified with 3 mL of 1 N acetic acid solution and extracted with ethyl acetate. The organic phase is washed with water, dried over magnesium sulfate, filtered and evaporated. The residue obtained is recrystallized from hot ethyl acetate. 630 mg (82%) of (Z)-2-methoxy-3-[3′-(1-methyl-3-pentylureido)biphenyl-4-yl]acrylic acid are obtained in the form of a white solid with a melting point of 144° C.
CCCCCNC(=O)N(C)c1cccc(-c2ccc(/C=C(\OC)C(=O)O)cc2)c1
null
CCCCCNC(=O)N(C)c1cccc(-c2ccc(/C=C(\OC)C(=O)OC)cc2)c1
null
null
[OH-].[Na+].[CH3:3][O:4]/[C:5](=[CH:10]\[C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([N:23]([CH3:32])[C:24]([NH:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[O:25])[CH:18]=2)=[CH:13][CH:12]=1)/[C:6]([O:8]C)=[O:7].C(O)(=O)C>O1CCCC1>[CH3:3][O:4]/[C:5](=[CH:10]\[C:11]1[CH:12]=[CH:13][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([N:23]([CH3:32])[C:24]([NH:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[O:25])[CH:18]=2)=[CH:15][CH:16]=1)/[C:6]([OH:8])=[O:7]
4
C1CCOC1
CC(=O)O
null
68
83.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,322,900
null
null
null
null
ord_dataset-cfad8b3f00044bcda60a96b019f09872
2013-01-01T00:08:00
true
N-(7-Chloro-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-6-piperazin-1-yl-nicotin-amide was prepared starting from intermediate E and piperazine. MS calcd. for C26H24ClN5O2 [(M+H)+] 474.2, obsd. 474.
O=C(NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O)c1ccc(N2CCNCC2)nc1
null
C1CNCCN1
O=C(NCc1cn(-c2ccccc2)c2cc(Cl)ccc2c1=O)c1ccc(Cl)nc1
null
Cl[C:2]1[CH:29]=[CH:28][C:5]([C:6]([NH:8][CH2:9][C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][C:15]([Cl:21])=[CH:16][CH:17]=3)[N:12]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:11]=2)=[O:7])=[CH:4][N:3]=1.[NH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1>>[Cl:21][C:15]1[CH:14]=[C:13]2[C:18]([C:19](=[O:20])[C:10]([CH2:9][NH:8][C:6](=[O:7])[C:5]3[CH:28]=[CH:29][C:2]([N:30]4[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]4)=[N:3][CH:4]=3)=[CH:11][N:12]2[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[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
1,176,526
null
null
null
null
ord_dataset-0f9d2dbe929a45c3892ae75e81e99443
2012-01-01T00:06:00
true
Method G1 was used with 8-(3-aminophenoxy)pyrido[2,3-b]pyrazin-2(1H)-one and 3-trifluoromethoxybenzoyl chloride to afford the title compound as a white solid (35 mg, 20%).
O=C(Nc1cccc(Oc2ccnc3ncc(=O)[nH]c23)c1)c1cccc(OC(F)(F)F)c1
null
Nc1cccc(Oc2ccnc3ncc(=O)[nH]c23)c1
O=C(Cl)c1cccc(OC(F)(F)F)c1
null
[NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[O:5][C:6]1[C:15]2[NH:14][C:13](=[O:16])[CH:12]=[N:11][C:10]=2[N:9]=[CH:8][CH:7]=1.[F:20][C:21]([F:33])([F:32])[O:22][C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[C:26](Cl)=[O:27]>>[O:16]=[C:13]1[CH:12]=[N:11][C:10]2[N:9]=[CH:8][CH:7]=[C:6]([O:5][C:4]3[CH:3]=[C:2]([NH:1][C:26](=[O:27])[C:25]4[CH:29]=[CH:30][CH:31]=[C:23]([O:22][C:21]([F:20])([F:32])[F:33])[CH:24]=4)[CH:19]=[CH:18][CH:17]=3)[C:15]=2[NH:14]1
null
null
null
null
null
null
20
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
16,166
NN
null
null
null
ord_dataset-b971427c0b944c56b63bb2356fa8ca69
1976-01-01T00:11:00
true
By the procedure similar to that described in Example 33, 1-phthalimidopropyl-3-phenyl-5-methylindazole (5.0 g) and hydrazine hydrate (1.5 g) were treated to obtain 3.1 g of 1-aminopropyl-3-phenyl-5-methylindazole as an oily product. The product was converted by a conventional way to its hydrochloride having a melting point between 161°-163° C.
CCC(N)c1c(C)ccc2[nH]nc(-c3ccccc3)c12
null
CCC(c1c(C)ccc2[nH]nc(-c3ccccc3)c12)N1C(=O)c2ccccc2C1=O
null
null
C1(=O)[N:5]([CH:6]([C:9]2[C:17]([CH3:18])=[CH:16][CH:15]=[C:14]3[C:10]=2[C:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:12][NH:13]3)[CH2:7][CH3:8])C(=O)C2=CC=CC=C12.O.NN>>[NH2:5][CH:6]([C:9]1[C:17]([CH3:18])=[CH:16][CH:15]=[C:14]2[C:10]=1[C:11]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[N:12][NH:13]2)[CH2:7][CH3:8]
null
O
null
null
null
null
92.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,137,958
[Pd+2]
CC(=O)[O-]
null
null
ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820
2012-01-01T00:02:00
true
To a solution of {(R)-4-[(3-isopropenyl-5-trifluoromethyl-benzenesulfonyl)-methyl-amino]-4,5,6,7-tetrahydro-indazol-1-yl}-acetic acid ethyl ester (70.7 mg, 0.15 mmol) in tetrahydrofuran (2 mL) was added a solution of diazomethane in diethyl ether (1M, 8 mL) slowly at 0° C. under an argon atmosphere, and then a portion of palladium acetate (5 mg) was added. After the mixture was stirred for 10 minutes, a second portion of palladium acetate (5 mg) was added and the mixture was stirred for another 20 minutes, followed by addition of a second portion of a solution of diazomethane in diethyl ether (1M, 5 mL). After being stirred at 0° C. for 2 hours under an argon atmosphere, the reaction mixture was then quenched by the addition of a few drops of acetic acid, and then filtered through a glass funnel and concentrated in vacuo. The residue was purified by flash column (gradient elution, 0-10% methanol in dichloromethane) to afford ((R)-4-{methyl-[3-(1-methyl-cyclopropyl)-5-trifluoromethyl-benzenesulfonyl]-amino}-4,5,6,7-tetrahydro-indazol-1-yl)-acetic acid ethyl ester (74.5 mg, 99%) as a colorless semisolid. MS cald. for C23H28F3N3O4S 499, obsd. (ESI+) [(M+H)+] 500.
CCOC(=O)Cn1ncc2c1CCC[C@H]2N(C)S(=O)(=O)c1cc(C(F)(F)F)cc(C2(C)CC2)c1
null
C=[N+]=[N-]
C=C(C)c1cc(C(F)(F)F)cc(S(=O)(=O)N(C)[C@@H]2CCCc3c2cnn3CC(=O)OCC)c1
null
[CH2:1]([O:3][C:4](=[O:33])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][C@@H:10]([N:15]([S:17]([C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]([CH3:32])=[CH2:31])[CH:21]=3)(=[O:19])=[O:18])[CH3:16])[C:9]=2[CH:8]=[N:7]1)[CH3:2].[N+](=[CH2:36])=[N-]>O1CCCC1.C(OCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][C:4](=[O:33])[CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][C@@H:10]([N:15]([CH3:16])[S:17]([C:20]3[CH:25]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:23]=[C:22]([C:30]4([CH3:36])[CH2:32][CH2:31]4)[CH:21]=3)(=[O:18])=[O:19])[C:9]=2[CH:8]=[N:7]1)[CH3:2]
0.17
CCOCC
C1CCOC1
null
null
99
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,585,657
Cl
null
null
null
ord_dataset-380e279f82154dba9e08ab51b3bdd08a
2015-01-01T00:05:00
true
To a mixture of EXAMPLE 402A (2.3 g) in acetic acid (40 ml) was added concentrated hydrochloric acid (3 ml). The mixture was heated at 80° C. for 4 hours. After cooling to room temperature, precipitation of the product occurred. Water (50 mL) was added to further induce precipitation. The solid was filtered, rinsed with water and dried in vacuo.
CCOC(=O)c1[nH]c2c(Br)ccc(F)c2c1CCC(=O)O
null
CCOC(=O)CCc1c(C(=O)OCC)[nH]c2c(Br)ccc(F)c12
null
null
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:23])=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:7]2[CH2:16][CH2:17][C:18]([O:20]CC)=[O:19].Cl>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:23])=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:7]2[CH2:16][CH2:17][C:18]([OH:20])=[O:19]
null
CC(=O)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
202,153
null
null
null
null
ord_dataset-19e5fc80c1554f4f8641c835e055f02b
1990-01-01T00:01:00
true
73.0 g (239 mmol) Methyl 5-acetamido-3-benzylthiopyrazole-4-carboxylate was dissolved in 470 ml methylene chloride and treated with 124.15 g silica gel and 25.6 g water and cooled to 0° C. 160.6 g (1.19 mol) Sulphuryl chloride in 730 ml methylene chloride was added dropwise. The mixture was stirred for 3 hours at 0° C., filtered, washed several times with methylene chloride, dried over magnesium sulphate and concentrated. The residue was triturated with ether/hexane, the crystals suction filtered, washed with hexane and dried.
COC(=O)c1c(S(=O)(=O)Cl)n[nH]c1NC(C)=O
null
COC(=S)c1c(Cc2ccccc2)n[nH]c1NC(C)=O
O=S(=O)(Cl)Cl
O
[C:1]([NH:4][C:5]1[NH:9][N:8]=[C:7](CC2C=CC=CC=2)[C:6]=1[C:17]([O:19][CH3:20])=S)(=[O:3])[CH3:2].[OH2:21].[S:22]([Cl:26])(Cl)(=[O:24])=[O:23]>C(Cl)Cl>[C:1]([NH:4][C:5]1[NH:9][N:8]=[C:7]([S:22]([Cl:26])(=[O:24])=[O:23])[C:6]=1[C:17]([O:19][CH3:20])=[O:21])(=[O:3])[CH3:2]
3
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
1,071,077
Cl
null
null
null
ord_dataset-5df93261afc143c3ae919a57ff4fc1d4
2011-01-01T00:07:00
true
To a solution of tert-butyl (S)-3-(2-methoxyethyl)piperidine-1-carboxylate (64 g, 263 mmol) in ethyl acetate (100 ml) was added 4N HCl-ethyl acetate solution (320 ml), and the mixture was stirred at room temperature for 2 hr. The solvent was evaporated under reduced pressure to give (S)-3-(2-methoxyethyl)piperidine hydrochloride as a crude product (46.7 g, yield 98%). The obtained crude product was used for Step 4 without further purification.
COCC[C@@H]1CCCNC1
null
COCC[C@@H]1CCCN(C(=O)OC(C)(C)C)C1
null
null
[CH3:1][O:2][CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6]1.[ClH:18].C(OCC)(=O)C>C(OCC)(=O)C>[ClH:18].[CH3:1][O:2][CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][NH:7][CH2:6]1
2
CCOC(C)=O
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
691,481
null
null
null
null
ord_dataset-6214af00a7eb47f3887ef21a94320a7e
2005-01-01T00:11:00
true
Preparation of example 52 from the title compound of Example 51 (32 mg, 0.050 mmol) and 45% TFA in CH2Cl2 (1 mL) was carried out analogously to Example 20. (Deprotection of trityl group was effected using the same conditions as for tert-butoxycarbonyl deprotection.) Isolation, also in an analogous manner, additionally included recrystallization from methanol/ethyl acetate and diethyl ether to afford the title compound (16 mg, 0.031 mmol) as a yellow powder in 62% yield.
O=C(CCc1c[nH]cn1)Nc1cc2c3c(c(-c4ccccc4)[nH]c3c1)C=NNC2=O
null
O=C(CCc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1)Nc1cc2c3c(c(-c4ccccc4)[nH]c3c1)C=NNC2=O
null
null
[O:1]=[C:2]1[C:13]2[C:14]3[C:6](=[C:7]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)[NH:8][C:9]=3[CH:10]=[C:11]([NH:15][C:16](=[O:43])[CH2:17][CH2:18][C:19]3[N:20]=[CH:21][N:22](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[CH:23]=3)[CH:12]=2)[CH:5]=[N:4][NH:3]1.[C:50]([OH:56])([C:52]([F:55])([F:54])[F:53])=[O:51]>C(Cl)Cl>[F:53][C:52]([F:55])([F:54])[C:50]([OH:56])=[O:51].[NH:22]1[CH:23]=[C:19]([CH2:18][CH2:17][C:16]([NH:15][C:11]2[CH:12]=[C:13]3[C:2](=[O:1])[NH:3][N:4]=[CH:5][C:6]4=[C:7]([C:44]5[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=5)[NH:8][C:9]([CH:10]=2)=[C:14]34)=[O:43])[N:20]=[CH:21]1
null
ClCCl
O=C(O)C(F)(F)F
null
null
null
62
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
917,165
null
null
null
null
ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d
2009-01-01T00:11:00
true
The title compound is prepared as described in EXAMPLE 123, using 1-(4-aminoquinazoline-7-ylmethyl)-3-propyl-piperazine-2-one, EXAMPLE 78 and 5-chloro-2-thienyloxyacetic acid, EXAMPLE 24. 1H NMR (d6-DMSO, 300 MHz) δ9.78 (bs, 2H), 8.81 (s, 1H), 8.35 (d, 1H), 7.60 (m, 2H), 7.51 (s, 1H), 6.69 (m, 1H), 6.21 (d, 1H), 4.91 (AB, 2H), 4.72 (m, 2H), 3.84 (m, 1H), 3.52 (m, 2H), 3.23 (m, 1H), 1.80 (m, 2H), 1.24 (m, 2H), 0.82 (m, 3H). MS (ion spray), m/z, 474, 476, (M+H) (Cl pattern). Elemental analysis, cal C22H22ClN5O2S.C2HF3O2.1.15H2O % C=47.31, % H=4.52, % N=11.50; found % C=47.39, % H=4.140, % N=11.19.
CCC[C@H]1C(=O)N(Cc2ccc3c(N)ncnc3c2)CCN1C(=O)COc1ccc(Cl)s1
null
CCCC1NCCN(Cc2ccc3c(N)ncnc3c2)C1=O
O=C(O)COc1ccc(Cl)s1
null
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][NH:16][CH:15]([CH2:19][CH2:20][CH3:21])[C:14]3=[O:22])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:23][C:24]1[S:28][C:27]([O:29][CH2:30][C:31](O)=[O:32])=[CH:26][CH:25]=1>>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:31](=[O:32])[CH2:30][O:29][C:27]4[S:28][C:24]([Cl:23])=[CH:25][CH:26]=4)[C@@H:15]([CH2:19][CH2:20][CH3:21])[C:14]3=[O:22])=[CH:9][CH:10]=2)[N:5]=[CH:4][N: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
1,113,372
[Pd]
null
null
null
ord_dataset-375a420ee9b042918ddca20f02df37d3
2011-01-01T00:11:00
true
To a solution of rel-N-[(3R,4R)-4-(allyloxy)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]-2-[4-(trifluoromethyl)-1H-benzimidazol-2-yl]acetamide in methanol was added Pd/C and the reaction was exposed to 1 atm H2 overnight. The reaction mixture was filtered and concentrated to afford rel-N-[(3R,4R)-4-propoxy-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]-2-[4-(trifluoromethyl)-1H-benzimidazol-2-yl]acetamide as a white solid. 1H-NMR (CDCl3) δ: 0.87 (t, 3H), 1.48-1.58 (m, 4H), 1.74 (m, 2H), 1.89 (m, 2H), 2.24-2.35 (m, 2H), 2.73 (m, 2H), 3.31-3.40 (m, 4H), 3.56 (m, 1H), 3.73 (m, 1H), 3.92-3.98 (m, 2H), 3.92 (s, 2H), 4.28 (m, 1H), 7.14 (b, 1H), 7.30 (t, J=7.9 Hz, 1H), 7.49 (d, J=7.3 Hz, 1H). MS m/z: 455 (M+1).
CCCO[C@@H]1CN(C2CCOCC2)C[C@H]1NC(=O)Cc1nc2c(C(F)(F)F)cccc2[nH]1
null
C=CCO[C@@H]1CN(C2CCOCC2)C[C@H]1NC(=O)Cc1nc2c(C(F)(F)F)cccc2[nH]1
null
null
[CH2:1]([O:4][C@@H:5]1[CH2:9][N:8]([CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH2:7][C@H:6]1[NH:16][C:17](=[O:32])[CH2:18][C:19]1[NH:23][C:22]2[CH:24]=[CH:25][CH:26]=[C:27]([C:28]([F:31])([F:30])[F:29])[C:21]=2[N:20]=1)[CH:2]=[CH2:3]>CO.[Pd]>[CH2:1]([O:4][C@@H:5]1[CH2:9][N:8]([CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH2:7][C@H:6]1[NH:16][C:17](=[O:32])[CH2:18][C:19]1[NH:23][C:22]2[CH:24]=[CH:25][CH:26]=[C:27]([C:28]([F:29])([F:31])[F:30])[C:21]=2[N:20]=1)[CH2:2][CH3:3]
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
1,316,300
O=C=O
[Li]CCCC
null
null
ord_dataset-2d6edb8ffd434003bb508360153bd9bb
2013-01-01T00:07:00
true
n-Butyl lithium (2.5M in hexanes, 0.23 mL, 0.56 mmol) was added dropwise to a solution of the product of example 87 (200 mg, 0.38 mmol) in tetrahydrofuran (8 mL), cooled to −78° C., and the mixture was stirred for 30 minutes. Carbon dioxide was then passed through the solution, with stirring at −78° C., for 3.5 hours before the mixture was allowed to warm to room temperature. The reaction mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate (30 mL) and water (20 mL). The organic layer was separated, washed with water, dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by column chromatography on silica gel, eluting with dichloromethane:methanol:0.88 ammonia, 100:0:0 to 98:2:0.2, afforded the title compound as a by-product, as an off white solid in 68% yield, 116 mg.
CC(C)(CCC(C#N)(c1ccccc1)c1ccccc1)N1CCC(OCc2ccccc2)CC1
N
CC(C)(CCC(C#N)(c1ccccc1)c1ccccc1)N1CCC(OCc2cccc(Br)c2)CC1
null
null
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]([CH:38]=[CH:39][CH:40]=1)[CH2:10][O:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]([CH3:37])([CH3:36])[CH2:19][CH2:20][C:21]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:22]#[N:23])[CH2:14][CH2:13]1.C(=O)=O>O1CCCC1>[NH3:15].[CH2:10]([O:11][CH:12]1[CH2:13][CH2:14][N:15]([C:18]([CH3:37])([CH3:36])[CH2:19][CH2:20][C:21]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:22]#[N:23])[CH2:16][CH2:17]1)[C:9]1[CH:8]=[CH:7][CH:40]=[CH:39][CH:38]=1
0.5
C1CCOC1
null
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
16,792
null
null
null
null
ord_dataset-d625331704b34593871e69cd09a5cd83
1976-01-01T00:12:00
true
3-Chloro-6,7-dimethyl-2quinoxalinecarboxylic acid (10.5 g) and N,N'-carbonyldiimidazole (7.35 g) in tetrahydrofuran (350 ml) were heated under reflux for 1 hour. 5-Amino-1H-tetrazole (4.3 g) in dimethylformamide (10 ml) was added and the mixture was heated under reflux for a further hour and cooled. The solid was collected and dissolved in aqueous dimethylaminoethanol. Dilute hydrochloric acid was added to the solution and the solid was collected and crystallised from dimethylformamide. The product decomposed at 360° (39%).
Cc1cc2nc(Cl)c(C(=O)Nc3nnn[nH]3)nc2cc1C
null
Nc1nnn[nH]1
Cc1cc2nc(Cl)c(C(=O)O)nc2cc1C
null
[Cl:1][C:2]1[C:3]([C:14]([OH:16])=O)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([CH3:12])=[C:7]([CH3:13])[CH:6]=2.[NH2:17][C:18]1[NH:22][N:21]=[N:20][N:19]=1>O1CCCC1.CN(C)C=O>[Cl:1][C:2]1[C:3]([C:14]([NH:17][C:18]2[NH:22][N:21]=[N:20][N:19]=2)=[O:16])=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([CH3:12])=[C:7]([CH3:13])[CH:6]=2
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
880,455
Cl[Sn]Cl
null
null
null
ord_dataset-3592bd645cd143ee8274cd0d834ae581
2009-01-01T00:05:00
true
N′-[(2′-Nitro-1,1′-biphenyl-4-yl)methyl]-N′-pentyl-N-(2,4,6-trifluorophenyl)urea (196.0 mg) and anhydrous tin(II) chloride (401.6 mg) were added to ethanol (4 mL), and the mixture was heated under reflux. One hour later, the solvent was distilled off, and ethyl acetate (15 mL) and a saturated sodium bicarbonate solution (15 mL) were added to the residue. The resultant precipitate was filtered off through Celite. The filtrate was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford N′-[(2′-amino-1,1′-biphenyl-4-yl)methyl]-N′-pentyl-N-(2,4,6-trifluorophenyl)urea (179.2 mg). Yield: 94%.
CCCCCN(Cc1ccc(-c2ccccc2N)cc1)C(=O)Nc1c(F)cc(F)cc1F
null
CCCCCN(Cc1ccc(-c2ccccc2[N+](=O)[O-])cc1)C(=O)Nc1c(F)cc(F)cc1F
null
null
[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][N:17]([CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[C:18](=[O:29])[NH:19][C:20]2[C:25]([F:26])=[CH:24][C:23]([F:27])=[CH:22][C:21]=2[F:28])=[CH:12][CH:11]=1)([O-])=O.[Sn](Cl)Cl>C(O)C>[NH2:1][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[CH:11]=[CH:12][C:13]([CH2:16][N:17]([CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[C:18](=[O:29])[NH:19][C:20]2[C:21]([F:28])=[CH:22][C:23]([F:27])=[CH:24][C:25]=2[F:26])=[CH:14][CH:15]=1
null
CCO
null
null
null
null
97.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
376,153
O=C([O-])O
[Na+]
null
null
ord_dataset-846d411edee44814931e062174d7ef12
1997-01-01T00:09:00
true
In an argon atmosphere; to a tetrahydrofuran solution (1 ml) of 52 mg (0.15 mmol) of octaethylcyclotetrasilane was added 0.56 ml (0.15 mmol) of a tetrahydrofuran solution (0.27M) of phenyldimethylsilyllithium, and stirred at 0° C. for 15 minutes. Phenyldimethylchlorosilane in an amount of 26 mg (0.15 mmol) was added, and reacted at room temperature for 3 hours. Hexane (2 ml) and saturated aqueous sodium bicarbonate solution (2 ml) were added, stirred, the hexane layer was separated, and dried with magnesium sulfate, The resulting crude product was purified by a silica gel column chromatography (hexane) to give 42 mg (46% yield) of 2,2,3,3,4,4,5,5-octaethyl-1,1,6,6-tetramethyl-1,6-diphenylhexasilane (1).
CC[Si](CC)([Si](C)(C)c1ccccc1)[Si](CC)(CC)[Si](CC)(CC)[Si](CC)(CC)[Si](C)(C)c1ccccc1
null
CC[Si]1(CC)[Si](CC)(CC)[Si](CC)(CC)[Si]1(CC)CC
[Li][Si](C)(C)c1ccccc1
C[Si](C)(Cl)c1ccccc1
[CH2:1]([Si:3]1([CH2:19][CH3:20])[Si:6]([CH2:9][CH3:10])([CH2:7][CH3:8])[Si:5]([CH2:13][CH3:14])([CH2:11][CH3:12])[Si:4]1([CH2:17][CH3:18])[CH2:15][CH3:16])[CH3:2].[C:21]1([Si:27]([Li])([CH3:29])[CH3:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[C:31]1([Si:37]([CH3:40])([CH3:39])Cl)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)(O)[O-].[Na+]>CCCCCC.O1CCCC1>[CH2:9]([Si:6]([CH2:7][CH3:8])([Si:3]([CH2:1][CH3:2])([CH2:19][CH3:20])[Si:4]([CH2:15][CH3:16])([CH2:17][CH3:18])[Si:5]([CH2:13][CH3:14])([CH2:11][CH3:12])[Si:37]([CH3:40])([CH3:39])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[Si:27]([CH3:29])([CH3:28])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:10]
0.25
CCCCCC
C1CCOC1
null
0
46
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
492,548
[Pd]
Cl
null
null
ord_dataset-3f9174c7efcb4f31becbd3516cde9572
2001-01-01T00:02:00
true
A solution of [5-benzyloxy-3-(2-dimethylamino-ethyl)-1H-indol-1yl]phenylmethanone (300 mg, 0.75 mmol) and 4N hydrochloric acid (190 ml, 0.76 mmol) in ethanol (10 ml) was hydrogenated over 10% palladium on carbon (100 mg) at 35 psi for 3 hours. The catalyst was removed by filtration. The filtrate was evaporated, and the residue was partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate. The aqueous was further extracted with dichloromethane (×2). The combined extracts were dried (K2CO3), filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with dichloromethane/methanol/aqueotus ammonia (80:8:1) to give the title compound (120 mg, 52%), as a colourless solid; mp 154°-156° C. δH (360 MHz, CDCl3) 2.40 (6H, s), 2.70-2.75 (2H, m), 2.83-2.88 (2H, m), 6.86-6.90 (2H, m), 7.04 (1H, s), 7.49-7.61 (3H, m), 7.68-7.71 (2H, m), 8.17 (0.5H, s), 8.20 (0.5H, s). m/z (CI+) 309 [MH]+. Found: C, 73.22; H, 6.48; N, 8.74. C19H20N2O2.0.2 H2O requires C, 73.15; H, 6.59; N, 8.98%.
CN(C)CCc1cn(C(=O)c2ccccc2)c2ccc(O)cc12
null
CN(C)CCc1cn(C(=O)c2ccccc2)c2ccc(OCc3ccccc3)cc12
null
null
C([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:19])[CH:13]=[C:12]2[CH2:26][CH2:27][N:28]([CH3:30])[CH3:29])C1C=CC=CC=1.Cl>C(O)C.[Pd]>[CH3:30][N:28]([CH3:29])[CH2:27][CH2:26][C:12]1[C:11]2[C:15](=[CH:16][CH:17]=[C:9]([OH:8])[CH:10]=2)[N:14]([C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:19])[CH:13]=1
null
CCO
null
null
null
null
51.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,602,933
[H-]
[Na+]
null
null
ord_dataset-9cecb3a8d3b9494191b28dcefea66af2
2015-01-01T00:07:00
true
To a suspension of NaH (2.6 g, 64 mmol, and 60.0% dispersion in oil) in DMF (80 mL) was added a solution of di-tert-butyl malonate (3.57 g, 16.50 mmol) in DMF (20 mL) at 0° C. and this was stirred for 15 min. Subsequently, 2,4,5-trifluorobenzonitrile (3.0 g, 15.0 mmol) was added in one portion and the reaction mixture was stirred for 8 h at 80° C. and three hours at room temperature. Water (50 mL) was added and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL), dried over MgSO4 and filtered. After evaporation in vacuo, the residue was purified by flash chromatography (20% EtOAc in hexane) to give 10.0 g of di-tert-butyl(4-cyano-2,5-difluorophenyl)propanedioate as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.51 (dd, J=5.5, J=5.4 Hz, 1H), 7.37 (dd, J=5, J=6 Hz, 1H), 4.84 (s, 1H), 1.50 (s, 18H). LC-MS (IE, m/z): 298.2 [(M+1)]+-t-Bu].
CC(C)(C)OC(=O)C(C(=O)OC(C)(C)C)c1cc(F)c(C#N)cc1F
null
N#Cc1cc(F)c(F)cc1F
CC(C)(C)OC(=O)CC(=O)OC(C)(C)C
null
[H-].[Na+].[C:3]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])(=[O:12])[CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[F:18][C:19]1[CH:26]=[C:25](F)[C:24]([F:28])=[CH:23][C:20]=1[C:21]#[N:22].O>CN(C=O)C>[C:14]([O:13][C:3](=[O:12])[CH:4]([C:25]1[CH:26]=[C:19]([F:18])[C:20]([C:21]#[N:22])=[CH:23][C:24]=1[F:28])[C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])([CH3:17])([CH3:16])[CH3:15]
0.25
CN(C)C=O
O
null
null
null
188.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,742,691
null
null
null
null
ord_dataset-60a3e71da3174666a50a61dcfa611a9f
2016-01-01T00:07:00
true
A mixture of N-((5-((6′-(bis(tert-butoxycarbonyl)amino)-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (0.23 g, 0.379 mmol) and TFA (0.44 mL, 5.7 mmol) in DCM (4 mL) was stirred at RT for 16 h. The mixture was concentrated to dryness, treated with satd. NaHCO3 and extracted with EtOAc (2×). The combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-((5-((6′-amino-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (125 mg, 81%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.21 (s, 1H), 10.45 (br s, 1H), 8.62 (d, J=2.5 Hz, 1H), 8.44 (d, J=5.7 Hz, 1H), 8.27 (d, J=2.9 Hz, 1H), 8.09 (d, J=9.0 Hz, 1H), 8.01 (dd, J=8.7, 2.5 Hz, 1H), 7.74 (dd, J=9.0, 2.9 Hz, 1H), 7.38 (d, J=2.4 Hz, 1H), 6.74 (dd, J=5.7, 2.4 Hz, 1H), 6.47 (d, J=8.7 Hz, 1H), 6.27 (d, J=4.7 Hz, 2H), 1.21 (s, 9H); MS (ESI) m/z: 407.2 (M+H+).
CC(C)(C)C(=O)NC(=O)Nc1ccc(Oc2ccnc(-c3ccc(N)nc3)c2)cn1
null
CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1ccc(-c2cc(Oc3ccc(NC(=O)NC(=O)C(C)(C)C)nc3)ccn2)cn1
null
null
C(OC([N:8](C(OC(C)(C)C)=O)[C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH:20]=[C:19]([O:21][C:22]3[CH:23]=[CH:24][C:25]([NH:28][C:29]([NH:31][C:32](=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34])=[O:30])=[N:26][CH:27]=3)[CH:18]=[CH:17][N:16]=2)=[CH:11][CH:10]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH:20]=[C:19]([O:21][C:22]3[CH:23]=[CH:24][C:25]([NH:28][C:29]([NH:31][C:32](=[O:37])[C:33]([CH3:35])([CH3:34])[CH3:36])=[O:30])=[N:26][CH:27]=3)[CH:18]=[CH:17][N:16]=2)=[CH:11][CH:10]=1
16
ClCCl
O=C(O)C(F)(F)F
null
25
null
81.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
678,276
null
null
null
null
ord_dataset-50cdc205280641d2a3e264f32908e3d0
2005-01-01T00:07:00
true
To a suspension of N-(4-fluorobenzyl)-8-hydroxy-5-(methylamino)-1,6-naphthyridine-7-carboxamide (2.65 g, 8.12 mmol) in methanol (50 mL) and CH2Cl2 (20 mL) was added trimethylsilyldiazomethane (12.1 ml of a 2M solution in hexanes, 24.4 mmol) and the mixture was stirred for 16 hr at rt. Additional trimethylsilyldiazomethane (24.0 ml of a 2M solution in hexanes, 48 mmol) was added and the reaction was stirred for 16 hr. The reaction was quenched by the addition of acetic acid (2 mL) and the solvent was evaporated in vacuo. The residue was purified by flash chromatography eluting with MeOH/CH2Cl2 (5-15% gradient elution), to afford the title compound.
CNc1nc(C(=O)NCc2ccc(F)cc2)c(OC)c2ncccc12
null
CNc1nc(C(=O)NCc2ccc(F)cc2)c(O)c2ncccc12
C[Si](C)(C)C=[N+]=[N-]
null
[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19]([OH:20])=[C:18]3[C:13]([CH:14]=[CH:15][CH:16]=[N:17]3)=[C:12]([NH:21][CH3:22])[N:11]=2)=[O:9])=[CH:4][CH:3]=1.[CH3:25][Si](C=[N+]=[N-])(C)C>CO.C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19]([O:20][CH3:25])=[C:18]3[C:13]([CH:14]=[CH:15][CH:16]=[N:17]3)=[C:12]([NH:21][CH3:22])[N:11]=2)=[O:9])=[CH:23][CH:24]=1
16
ClCCl
CO
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
636,783
CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
CN(C)c1ccncc1
null
null
ord_dataset-a192df1b44174b5886ef2005f759d553
2004-01-01T00:05:00
true
N-[2-(5-Nitro-1H-indol-3-yl)-ethyl]-acetamide (0.6 mmol) is taken into acetonitrile (1 mL) and stirred with a catalytic amount of DMAP and di-t-butyl dicarbonate (0.7 mmol) for 1 h. The solvent is removed in vacuo and the remaining oil chromatographed with ethyl acetate-hexane as eluent. The product is dissolved in ethanol (10 ml) and hydrogenated as above. The residue is dissolved in DMF (2 mL), and diisopropylethylamine (1.4 mmol) followed by methyl iodide (1.4 mmol) added. The mixture is stirred 3 h at 25° C. then filtered, evaporated to dryness, dissolved in ethanol and decolorized with activated charcoal. The residue is dissolved in trifluoroacetic acid with 1 equivalent of thiophenol and stirred 1 h at 20° C. The solvent is removed, the compound dissolved in isopropanol-water (5:1) and treated with 2 equivalents (w/w) of Dowex AG1-X8 ion exchange resin in the hydroxide form. Evaporation of the solvent followed by crystallization affords the title compound.
CC(=O)NCCc1c[nH]c2ccc(N(C)C)cc12
null
CCN(C(C)C)C(C)C
Sc1ccccc1
CC(=O)NCCc1c[nH]c2ccc([N+](=O)[O-])cc12
[N+](C1C=C2C(=CC=1)[NH:9][CH:8]=[C:7]2[CH2:13][CH2:14][NH:15][C:16](=[O:18])[CH3:17])([O-])=O.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.[CH:34]([N:37](C(C)C)[CH2:38]C)(C)C.CI.[C:45]1(S)[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>CN(C1C=CN=CC=1)C.FC(F)(F)C(O)=O.C(#N)C>[CH3:34][N:37]([CH3:38])[C:47]1[CH:46]=[C:45]2[C:50](=[CH:49][CH:48]=1)[NH:9][CH:8]=[C:7]2[CH2:13][CH2:14][NH:15][C:16](=[O:18])[CH3:17]
3
CI
CC#N
O=C(O)C(F)(F)F
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
1,690,686
null
null
null
null
ord_dataset-c1e70ad912eb438f8d34b1dc681f809a
2016-01-01T00:02:00
true
In analogy to the procedure described for the preparation of example 37, 6-(5-aminomethyl-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-one (example 36) has been reacted with cyclopropanecarboxylic acid to give the title compound as a white solid. MS: 336.3 (M+H+).
CN1C(=O)CCc2cc(-c3cncc(CNC(=O)C4CC4)c3)ccc21
null
CN1C(=O)CCc2cc(-c3cncc(CN)c3)ccc21
O=C(O)C1CC1
null
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH2:13][CH2:12]3)[CH:6]=[N:7][CH:8]=1.[CH:21]1([C:24](O)=[O:25])[CH2:23][CH2:22]1>>[CH3:19][N:15]1[C:16]2[C:11](=[CH:10][C:9]([C:5]3[CH:4]=[C:3]([CH2:2][NH:1][C:24]([CH:21]4[CH2:23][CH2:22]4)=[O:25])[CH:8]=[N:7][CH:6]=3)=[CH:18][CH:17]=2)[CH2:12][CH2:13][C:14]1=[O:20]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,705,805
O=C(n1ccnc1)n1ccnc1
null
null
null
ord_dataset-54347fcace774f89850681d6dec8009f
2016-01-01T00:03:00
true
6-Phenylhexanoic acid (0.100 g, 0.52 mmol) and CDI (0.169 g, 1.04 mmol) were added together and then reacted with nitropropane (0.070 g, 0.78 mmol) and DBU (0.198 g, 1.30 mmol) according to the general procedure. Purification by column chromatography gave 0.059 g (43%) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.28 (m, 2H), 7.17 (m, 3H), 5.04 (dd, J=4.4, 9.6 Hz, 1H), 2.60 (m, 4H), 1.62 (m, 6H), 1.31 (m, 2H) 1.02 (t, J=7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 199.3, 142.5, 128.6, 128.5, 126.0, 95.8, 39.5, 35.9, 31.3, 28.7, 23.5, 23.3, 10.6 ppm; IR νmax (cm−1) 2922, 2855, 1730, 1559, 1454, 1363, 1030, 747, 699; HRMS (FAB) calcd for C15H21NO3 (MNa+) 286.1414, found 286.1410.
CCC(C(=O)CCCCCc1ccccc1)[N+](=O)[O-]
null
O=C(O)CCCCCc1ccccc1
CCC[N+](=O)[O-]
null
[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[N+:27]([CH2:30][CH2:31][CH3:32])([O-:29])=[O:28].C1CCN2C(=NCCC2)CC1>>[N+:27]([CH:30]([C:12](=[O:14])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[CH2:31][CH3:32])([O-:29])=[O:28]
null
C1CCC2=NCCCN2CC1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
48,121
BrBr
[Mg]
null
null
ord_dataset-b43eb0158fd54801957aaa07bbdf3057
1978-01-01T00:11:00
true
To a stirred suspension of 1.5 g of magnesium turnings in 10 ml of dry tetrahydrofuran, add a small amount of 4'-trifluoromethyl-4-bromo[1,1']biphenyl and a few drops of bromine. When the reaction is started, add (dropwise) a solution of 16 g of 4'-trifluoromethyl-4-bromo-[1,1']biphenyl in 50 ml of tetrahydrofuran at 50°-60° C. Heat the mixture for one hour, cool to 0° C., and slowly (dropwise) add 7 g of acetaldehyde. Stir the reaction mixture at room temperature for twenty hours. Work-up the reaction mixture following the procedure of example 2, and isolate the desired product by chromatography, m.p. 116°-117°.
CC(O)c1ccc(-c2ccc(C(F)(F)F)cc2)cc1
null
CC=O
FC(F)(F)c1ccc(-c2ccc(Br)cc2)cc1
null
[Mg].[F:2][C:3]([F:18])([F:17])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13](Br)=[CH:12][CH:11]=2)=[CH:6][CH:5]=1.[CH:19](=[O:21])[CH3:20]>O1CCCC1.BrBr>[F:2][C:3]([F:18])([F:17])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([CH:19]([OH:21])[CH3:20])=[CH:12][CH:11]=2)=[CH:6][CH:5]=1
null
C1CCOC1
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
996,897
null
null
null
null
ord_dataset-b6d8835b0c934476a36e6149e7597487
2010-01-01T00:09:00
true
In a manner analogous to the preparation of N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine, the reaction of benzothiophen-3-ylmethylamine (244 mg, 1.5 mmol) and 2,4-dichloro-5-fluoropyrimidine (50 mg, 0.3 mmol) gave N4-(benzothiophen-3-ylmethyl)-2-chloro-5-fluoro-4-pyrimidineamine. The reaction of N4-(benzothiophen-3-ylmethyl)-2-chloro-5-fluoro-4-pyrimidineamine and 3-aminophenol (200 mg, 1.83 mmol) gave N4-(benzothiophen-3-ylmethyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine. (40 mg, 36%). 1H NMR (CDCl3): δ 4.45 (br, 1H), 4.95 (dd, J=1.2 and 5.4 Hz, 2H), 5.33 (br, 1H), 6.40 (ddd, J=1.2, 2.4 and 8.1 Hz, 1H), 6.85 (ddd, J=0.9, 2.1 and 8.1 Hz, 1H), 6.91 (br, 1H), 7.05 (t, J=8.1 Hz, 1H), 7.26 (m, 1H), 7.39-7.47 (m, 3H), 7.81 (dd, J=1.2 and 5.1 Hz, 1H), 7.84 (d, J=3.3 Hz, 1H), 7.92 (m, 1H); 19F NMR (282 MHz, CDCl3): δ −168.89; LCMS: ret. time: 21.91 min.; purity: 99.34%; MS (m/e): 366.96 (MH+).
Oc1cccc(Nc2ncc(F)c(NCc3csc4ccccc34)n2)c1
null
Nc1cccc(O)c1
Fc1cnc(Cl)nc1NCc1csc2ccccc12
null
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([CH2:10][NH:11][C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14](Cl)[N:13]=2)=[CH:2]1.[NH2:20][C:21]1[CH:22]=[C:23]([OH:27])[CH:24]=[CH:25][CH:26]=1>>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([CH2:10][NH:11][C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([OH:27])[CH:22]=3)[N:13]=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
822,503
Cc1ccccc1S(=O)(=O)O
O=C([O-])O
[Na+]
null
ord_dataset-ec58fad8331a42c5a67ad75aac6713b4
2008-01-01T00:05:00
true
47 ml of dihydropyran and 0.96 g of pyridine toluenesufonate were added at room temperature to 15.29 g of 11-keto-3-methoxy-estra-1,3,5(10),8-tetraen-17β-ol (1) in 35 ml of dichloromethane, and it was stirred for 2 hours. Then, the reaction solution was shaken several times with saturated sodium bicarbonate solution, washed with water and dried with magnesium sulfate. The solvent was evaporated in a vacuum, and the residue was purified on silica gel (solvent mixture: cyclohexane/ethyl acetate=8/2). 16.8 g (83%) of light yellowish, viscous oil was thus obtained.
COc1ccc2c(c1)CCC1=C2C(=O)C[C@]2(C)[C@@H](OC3CCCCO3)CC[C@@H]12
null
C1=COCCC1
COc1ccc2c(c1)CCC1=C2C(=O)C[C@]2(C)[C@@H](O)CC[C@@H]12
null
[O:1]1[CH:6]=[CH:5][CH2:4][CH2:3][CH2:2]1.C1(C)C(S(O)(=O)=O)=CC=CC=1.N1C=CC=CC=1.[O:24]=[C:25]1[CH2:42][C@@:40]2([CH3:41])[C@@H:36]([CH2:37][CH2:38][C@@H:39]2[OH:43])[C:35]2[CH2:34][CH2:33][C:32]3[CH:31]=[C:30]([O:44][CH3:45])[CH:29]=[CH:28][C:27]=3[C:26]1=2.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:45][O:44][C:30]1[CH:29]=[CH:28][C:27]2[C:26]3[C:25](=[O:24])[CH2:42][C@@:40]4([CH3:41])[C@@H:36]([CH2:37][CH2:38][C@@H:39]4[O:43][CH:6]4[CH2:5][CH2:4][CH2:3][CH2:2][O:1]4)[C:35]=3[CH2:34][CH2:33][C:32]=2[CH:31]=1
2
c1ccncc1
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
363,837
CN(C)c1ccncc1
O=C([O-])O
[Na+]
null
ord_dataset-c2ad1656a3ca4d08888ffb6e3f3a2742
1997-01-01T00:05:00
true
A mixture of 215 mg of the product of Example 43, 15 mg of 4-dimethylamino-pyridine, 1 ml of pyridine and 0.5 ml of acetic acid anhydride was stirred at room temperature for 30 minutes and was then poured into 20 ml of a saturated aqueous sodium bicarbonate solution. After stirring for 20 minutes, the mixture was extracted with ethyl acetate. The organic phase was washed with water and evaporated to dryness and the pyridine and residual acetic acid were distilled. The residue was chromatographed on silica and eluted with a 65-35 methylene chloride-ethyl acetate mixture. The residue with a Rf=0.35 was taken up in isopropanol, partially concentrated, iced and vacuum filtered to obtain after drying, 210 mg of the desired product melting at 99° C. to 100° C.
CC(=O)OCCN1C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=O)C1(C)C
null
CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=O)N1CCO
CC(=O)OC(C)=O
null
[CH3:1][C:2]1([CH3:24])[C:6](=[O:7])[N:5]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10]([C:16]([F:19])([F:18])[F:17])[CH:9]=2)[C:4](=[O:20])[N:3]1[CH2:21][CH2:22][OH:23].[C:25](OC(=O)C)(=[O:27])[CH3:26].C(=O)(O)[O-].[Na+]>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[C:25]([O:23][CH2:22][CH2:21][N:3]1[C:2]([CH3:24])([CH3:1])[C:6](=[O:7])[N:5]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10]([C:16]([F:17])([F:18])[F:19])[CH:9]=2)[C:4]1=[O:20])(=[O:27])[CH3:26]
0.5
c1ccncc1
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
168,048
Br
null
null
null
ord_dataset-01dbb772c5e249108f0b191ed17a2c0c
1988-01-01T00:02:00
true
A solution of 44.27 g (0.107 mole of N-[2-[(3,4-dichlorophenyl)sulfonyl]ethyl]-N-(1-methylethyl)carbamic acid phenyl ester in 300 ml of 48% HBr was heated at reflux for 12 hr. The reaction mixture was cooled to room temperature, made alkaline with 50% sodium hydroxide-ice and extracted with chloroform. The chloroform layer was extracted with 1N sulfuric acid. The sulfuric acid layer was extracted with chloroform and the chloroform layers combined and evaporated to an oil, the free base of the title compound. A portion of the oil was reacted with ethereal hydrogen chloride to give an overall yield of 32.4% white crystalline product, m.p. 219°-221° C.
CC(C)NCCS(=O)(=O)c1ccc(Cl)c(Cl)c1
null
CC(C)N(CCS(=O)(=O)c1ccc(Cl)c(Cl)c1)C(=O)Oc1ccccc1
null
null
C1(OC(=O)[N:9]([CH2:13][CH2:14][S:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)(=[O:17])=[O:16])[CH:10]([CH3:12])[CH3:11])C=CC=CC=1>Br>[Cl:25][C:20]1[CH:19]=[C:18]([S:15]([CH2:14][CH2:13][NH:9][CH:10]([CH3:12])[CH3:11])(=[O:16])=[O:17])[CH:23]=[CH:22][C:21]=1[Cl:24]
null
null
null
null
25
32.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
481,516
null
null
null
null
ord_dataset-21c1b1c06c7e4e09a38b5b1c71a32e52
2000-01-01T00:10:00
true
Analogously to Step 8.3,1.45 g of 6-(4-ethoxycarbonyl-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ol in 15 ml of phosphorus oxychloride are heated under a protective gas for 2 hours and worked up, yielding the title compound; m.p.: 250° C. (decomp.): TLC-Rf =0.63 (ethyl acetate/hexane [1:1]); FAB-MS: (M+H)+ =302.
CCOC(=O)c1ccc(-c2cc3c(Cl)ncnc3[nH]2)cc1
null
CCOC(=O)c1ccc(-c2cc3c(O)ncnc3[nH]2)cc1
O=P(Cl)(Cl)Cl
null
[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[NH:21][C:15]3[N:16]=[CH:17][N:18]=[C:19](O)[C:14]=3[CH:13]=2)=[CH:8][CH:7]=1)=[O:5])[CH3:2].P(Cl)(Cl)([Cl:24])=O>>[Cl:24][C:19]1[C:14]2[CH:13]=[C:12]([C:9]3[CH:10]=[CH:11][C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:7][CH:8]=3)[NH:21][C:15]=2[N:16]=[CH:17][N:18]=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
1,562,780
O=P([O-])([O-])[O-]
[K+]
null
null
ord_dataset-4e54080057a44c3887653391e24c90b6
2015-01-01T00:03:00
true
A solution of 6-bromo-4-(((3R,4S)-1-(5-cyanopyrimidin-2-yl)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (10 mg, 0.022 mmol) in 1,4-dioxane (0.5 mL), was added [1,1′-[bis(diphenylphosphino)ferrocene]-dicholorpalladium (II) (1.601 mg, 2.187 μmol), [4-(cyclopropylcarbamoyl)phenyl]-boronic acid (6.73 mg, 0.033 mmol) and potassium phosphate (2M, 0.033 mL, 0.066 mmol). The reaction vial was purged with nitrogen, sealed and heated at 140° C. for 1 h. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 25-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to give the title compound (4.2 mg, 35% yield). 1H NMR (500 MHz, METHANOL-d4) δ 8.57 (br. s., 1H), 8.51 (d, J=3.0 Hz, 1H), 8.13 (d, J=3.5 Hz, 1H), 7.95 (br. s., 1H), 7.87-7.75 (m, 2H), 7.73-7.66 (m, 2H), 7.62-7.55 (m, 2H), 7.18 (br. s., 1H), 5.09 (br. s., 1H), 4.33-4.22 (m, 2H), 4.02-3.94 (m, 1H), 3.93-3.84 (m, 1H), 3.77-3.69 (m, 1H), 3.52 (d, J=3.5 Hz, 3H), 2.89-2.80 (m, 1H), 0.80 (m, 4H). MS (ES+) m/z: 538.22 (M+H); LC retention time: 1.31 min (analytical HPLC Method I).
CO[C@H]1CN(c2ncc(C#N)cn2)C[C@H]1Nc1c(C(N)=O)cnn2cc(-c3ccc(C(=O)NC4CC4)cc3)cc12
null
O=C(NC1CC1)c1ccc(B(O)O)cc1
CO[C@H]1CN(c2ncc(C#N)cn2)C[C@H]1Nc1c(C(N)=O)cnn2cc(Br)cc12
null
Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@H:11]3[C@@H:15]([O:16][CH3:17])[CH2:14][N:13]([C:18]4[N:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][N:19]=4)[CH2:12]3)=[C:8]([C:26]([NH2:28])=[O:27])[CH:7]=[N:6][N:5]2[CH:29]=1.[CH:30]1([NH:33][C:34]([C:36]2[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=2)=[O:35])[CH2:32][CH2:31]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1>[C:24]([C:21]1[CH:20]=[N:19][C:18]([N:13]2[CH2:14][C@H:15]([O:16][CH3:17])[C@H:11]([NH:10][C:9]3[C:4]4[N:5]([CH:29]=[C:2]([C:39]5[CH:38]=[CH:37][C:36]([C:34](=[O:35])[NH:33][CH:30]6[CH2:32][CH2:31]6)=[CH:41][CH:40]=5)[CH:3]=4)[N:6]=[CH:7][C:8]=3[C:26]([NH2:28])=[O:27])[CH2:12]2)=[N:23][CH:22]=1)#[N:25]
0.42
C1COCCO1
null
null
140
null
35.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,277,514
CCN=C=NCCCN(C)C
Cl
On1nnc2ccccc21
null
ord_dataset-d5c54236ecd94d61aaa071461bcfc426
2013-01-01T00:04:00
true
To a mixture of 5-(2-methoxyethoxy)-7-[methyl(pyridin-2-ylsulfonyl)amino]-1H-indole-2-carboxylic acid (1.62 g), 1H-1,2,3-benzotriazol-1-ol (919 mg), 2-(benzylthio)-3,3-dimethoxy-2-methylpropan-1-amine (1.02 g) and N,N-dimethylformamide (30 mL) was added N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (1.53 g) at room temperature, and the mixture was added overnight at room temperature, and concentrated under reduced pressure. The residue was diluted with ethyl acetate and water. The organic layer was washed with saturated brine, dried over sodium sulfate, and filtrated, and the filtrate was concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to give the title compound (1.96 g, yield 76%) as a colorless amorphous solid from a fraction eluted with ethyl acetate-hexane (4:1).
COCCOc1cc(N(C)S(=O)(=O)c2ccccn2)c2[nH]c(C(=O)NCC(C)(SCc3ccccc3)C(OC)OC)cc2c1
null
COC(OC)C(C)(CN)SCc1ccccc1
COCCOc1cc(N(C)S(=O)(=O)c2ccccn2)c2[nH]c(C(=O)O)cc2c1
null
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[C:13]([N:15]([CH3:25])[S:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)(=[O:18])=[O:17])[CH:14]=1)[NH:11][C:10]([C:26](O)=[O:27])=[CH:9]2.N1(O)C2C=CC=CC=2N=N1.[CH2:39]([S:46][C:47]([CH3:55])([CH:50]([O:53][CH3:54])[O:51][CH3:52])[CH2:48][NH2:49])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[CH2:39]([S:46][C:47]([CH3:55])([CH:50]([O:51][CH3:52])[O:53][CH3:54])[CH2:48][NH:49][C:26]([C:10]1[NH:11][C:12]2[C:8]([CH:9]=1)=[CH:7][C:6]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:14][C:13]=2[N:15]([CH3:25])[S:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)(=[O:18])=[O:17])=[O:27])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1
null
CN(C)C=O
null
null
null
76.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
551,011
[Pd]
null
null
null
ord_dataset-e967d076b4894c2c854795f019ed3c39
2002-01-01T00:06:00
true
A mixture of (R)-3-[{N-(2-(tert-butoxycarbonylamino)-5-trifluoromethylbenzoyl)glycyl}amino]-1-(4,5-methylenedioxy-2-nitrobenzyl)pyrrolidine prepared above, 10% Pd-activated carbone (22 mg), and methanol (3.0 mL) was stirred under a hydrogen atmosphere at room temperature overnight. The Pd catalyst was filtered off, and the filtrate was concentrated to afford (R)-1-(2-amino-4,5-methylenedioxybenzyl)-3-[{N-(2-(tert-butoxycarbonylamino)-5-trifluoromethylbenzoyl)glycyl}amino]pyrrolidine (87.1 mg, quant.): Any remarkable by-products were not detected in TLC.
CC(C)(C)OC(=O)Nc1ccc(C(F)(F)F)cc1C(=O)NCC(=O)N[C@@H]1CCN(Cc2cc3c(cc2N)OCO3)C1
null
CC(C)(C)OC(=O)Nc1ccc(C(F)(F)F)cc1C(=O)NCC(=O)N[C@@H]1CCN(Cc2cc3c(cc2[N+](=O)[O-])OCO3)C1
null
null
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][C@@H:18]1[CH2:22][CH2:21][N:20]([CH2:23][C:24]2[CH:29]=[C:28]3[O:30][CH2:31][O:32][C:27]3=[CH:26][C:25]=2[N+:33]([O-])=O)[CH2:19]1)=[O:16])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2]>[Pd].CO>[NH2:33][C:25]1[CH:26]=[C:27]2[O:32][CH2:31][O:30][C:28]2=[CH:29][C:24]=1[CH2:23][N:20]1[CH2:21][CH2:22][C@@H:18]([NH:17][C:15](=[O:16])[CH2:14][NH:13][C:11](=[O:12])[C:10]2[CH:36]=[C:37]([C:40]([F:43])([F:41])[F:42])[CH:38]=[CH:39][C:9]=2[NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:19]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
1,101,794
O=C([O-])[O-]
[Cs+]
null
null
ord_dataset-af85e6f81c2d49f08086afd6d9e6959c
2011-01-01T00:10:00
true
A mixture of 2.82 g (10 mmole) of 2-amino-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid ethyl ester, 9.75 g (30 mmole) of cesium carbonate, 20 mL of dimethylformamide, and 2.15 g (10 mmole) of 4-dimethoxymethyl-2-fluoro-1-nitro-benzene was heated at 80 degrees for 1 hour. The cooled mixture was diluted with 200 mL of water and extracted three times with 100 mL of dichloromethane. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified with silica gel chromatography, eluting with ethyl acetate-hexanes (gradient 0:100-10:90) to give 3.4 g of 4-(3-chloro-phenyl)-2-(5-dimethoxymethyl-2-nitro-phenylamino)-thiazole-5-carboxylic acid ethyl ester (VI.41a) as a yellow solid.
CCOC(=O)c1sc(Nc2cc(C(OC)OC)ccc2[N+](=O)[O-])nc1-c1cccc(Cl)c1
null
CCOC(=O)c1sc(N)nc1-c1cccc(Cl)c1
COC(OC)c1ccc([N+](=O)[O-])c(F)c1
null
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH2:11])=[N:8][C:7]=1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=1)=[O:5])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O.[CH3:30][O:31][CH:32]([O:43][CH3:44])[C:33]1[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[C:35](F)[CH:34]=1>O>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([NH:11][C:35]2[CH:34]=[C:33]([CH:32]([O:43][CH3:44])[O:31][CH3:30])[CH:38]=[CH:37][C:36]=2[N+:39]([O-:41])=[O:40])=[N:8][C:7]=1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=1)=[O:5])[CH3:2]
null
O
CN(C)C=O
null
null
null
71.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,391,889
COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(Br)ccc(F)c43)ccc21
null
null
null
ord_dataset-12dc3bd21bcf44d09e5b4249afe15161
2014-01-01T00:02:00
true
The title compound is prepared from {(S)-6-[(R)-7-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester and 2-(4-bromo-3,5-dimethyl-phenyl)-3-methyl-pyridine following a procedure analogous to that described in Step 5 of Intermediate 1. LC (method 7): tR=1.07 min; Mass spectrum (ESI+): m/z=538 [M+H]+.
COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(-c5c(C)cc(-c6ncccc6C)cc5C)ccc(F)c43)ccc21
null
COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c(B5OC(C)(C)C(C)(C)O5)ccc(F)c43)ccc21
Cc1cccnc1-c1cc(C)c(Br)c(C)c1
null
[CH3:1][O:2][C:3](=[O:34])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C@H:15]3[C:23]4[C:18](=[C:19](B5OC(C)(C)C(C)(C)O5)[CH:20]=[CH:21][C:22]=4[F:24])[CH2:17][CH2:16]3)=[CH:13][C:8]=2[O:7][CH2:6]1.Br[C:36]1[C:41]([CH3:42])=[CH:40][C:39]([C:43]2[C:48]([CH3:49])=[CH:47][CH:46]=[CH:45][N:44]=2)=[CH:38][C:37]=1[CH3:50].BrC1C=CC(F)=C2C=1CC[C@H]2OC1C=CC2[C@H](CC(OC)=O)COC=2C=1>>[CH3:1][O:2][C:3](=[O:34])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C@H:15]3[C:23]4[C:18](=[C:19]([C:36]5[C:37]([CH3:50])=[CH:38][C:39]([C:43]6[C:48]([CH3:49])=[CH:47][CH:46]=[CH:45][N:44]=6)=[CH:40][C:41]=5[CH3:42])[CH:20]=[CH:21][C:22]=4[F:24])[CH2:17][CH2:16]3)=[CH:13][C:8]=2[O:7][CH2:6]1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
826,014
Cl
null
null
null
ord_dataset-0ca5627a13c049a99463095023b09fe5
2008-01-01T00:06:00
true
(R)-7-Amino-4-chloro-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one (130 mg, 390.7 μmol) was dissolved in N,N-dimethylformamide (5.0 mL). N,N-Diisopropylethylamine (200 μL, 1.1 mmol) was added to the mixture followed by diphenyl N-cyanocarbonimidate (100 mg, 407.1 μmol). Mixture stirred at room temperature for 40 minutes. 3-(Piperidin-4-yl)quinolin-2(1H)-one hydrochloride (125 mg; 472.1 μmol) was added to the vessel with stirring. The mixture was heated to 100° C. and held for 54 hr with stirring. Mixture was cooled to room temperature and then diluted with methanol. Mixture was filtered. Filtrate was purified by reverse phase prep HPLC (acetonitrile-water-ammonium acetate). Acetonitrile was removed from the fractions by roto-vap. Remaining aqueous was diluted with water. Solids were filtered off and washed with water. Air was pulled through the filter cake for 2 hours. Solids were collected and then dried in vacuo. Title compound was obtained as tan solid in 33% yield. 1H NMR (500 MHz, DMSO-D6) δ ppm 13.62 (s, 1 H) 11.79 (s, 1 H) 8.35 (s, 1H) 7.73 (s, 1 H) 7.66 (d, J=7.94 Hz, 1H) 7.53 (d, J=7.93 Hz, 1H) 7.44 (t, J=7.63 Hz, 1 H) 7.25-7.33 (m, 2 H) 7.16 (t, J=7.48 Hz, 1 H) 5.59-5.71 (m, 1 H) 5.40 (d, J=17.40 Hz, 1 H) 4.90 (d, J=17.70 Hz, 1 H) 4.59-4.77 (m, 1 H) 4.27 (d, J=13.12 Hz, 2H) 4.00-4.15 (m, 1 H) 3.33-3.42 (m, 1 H) 3.03-3.26 (m, 4 H) 1.86-1.98 (m, 2) 1.54-1.71 (m, 2 H). High resolution MS m/e (M+H)+=611.1890.
N#CN=C(N[C@@H]1Cc2cc(Cl)c3[nH]ncc3c2CN(CC(F)(F)F)C1=O)N1CCC(c2cc3ccccc3[nH]c2=O)CC1
null
N[C@@H]1Cc2cc(Cl)c3[nH]ncc3c2CN(CC(F)(F)F)C1=O
N#CN=C(Oc1ccccc1)Oc1ccccc1
O=c1[nH]c2ccccc2cc1C1CCNCC1
[NH2:1][C@H:2]1[C:16](=[O:17])[N:15]([CH2:18][C:19]([F:22])([F:21])[F:20])[CH2:14][C:5]2[C:6]3[CH:7]=[N:8][NH:9][C:10]=3[C:11]([Cl:13])=[CH:12][C:4]=2[CH2:3]1.C(N(CC)C(C)C)(C)C.C1C=CC(O[C:39](OC2C=CC=CC=2)=[N:40][C:41]#[N:42])=CC=1.Cl.[NH:51]1[CH2:56][CH2:55][CH:54]([C:57]2[C:58](=[O:67])[NH:59][C:60]3[C:65]([CH:66]=2)=[CH:64][CH:63]=[CH:62][CH:61]=3)[CH2:53][CH2:52]1>CN(C)C=O.CO>[Cl:13][C:11]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:14][N:15]([CH2:18][C:19]([F:21])([F:20])[F:22])[C:16](=[O:17])[C@H:2]([NH:1][C:39]([N:51]3[CH2:52][CH2:53][CH:54]([C:57]4[C:58](=[O:67])[NH:59][C:60]5[C:65]([CH:66]=4)=[CH:64][CH:63]=[CH:62][CH:61]=5)[CH2:55][CH2:56]3)=[N:40][C:41]#[N:42])[CH2:3][C:4]=2[CH:12]=1
0.67
CCN(C(C)C)C(C)C
CO
CN(C)C=O
25
33
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
904,122
null
null
null
null
ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4
2009-01-01T00:09:00
true
Piperazine-2-carboxylic acid methylamide from step (c) above (570 mg, 4.0 mmol) and (5,6-dichloro-pyridin-3-yl)-methanol (710 mg, 4.0 mmol, TCI-US) reacted under the conditions of Example 3a to give the title compound as a light-yellow gum. MS ESI, pos. ion) m/e: 285 (M+1).
CNC(=O)C1CN(c2ncc(CO)cc2Cl)CCN1
null
CNC(=O)C1CNCCN1
OCc1cnc(Cl)c(Cl)c1
null
[CH3:1][NH:2][C:3]([CH:5]1[CH2:10][NH:9][CH2:8][CH2:7][NH:6]1)=[O:4].[Cl:11][C:12]1[CH:13]=[C:14]([CH2:19][OH:20])[CH:15]=[N:16][C:17]=1Cl>>[CH3:1][NH:2][C:3]([CH:5]1[CH2:10][N:9]([C:17]2[C:12]([Cl:11])=[CH:13][C:14]([CH2:19][OH:20])=[CH:15][N:16]=2)[CH2:8][CH2:7][NH:6]1)=[O:4]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,094,134
null
null
null
null
ord_dataset-52a37d876ddb453e86de0c15fa233d29
2011-01-01T00:09:00
true
tert-Butyl 4-(4-fluorophenyl)-4-(((2-methyl-5-(trifluoromethyl)-2H-indazol-7-yl)methoxy)methyl)piperidine-1-carboxylate (26 mg, 0.050 mmol) was dissolved in trifluoroacetic acid (25% in dichloromethane, 2 mL) and stirred at room temperature for 15 min. The reaction was concentrated, and loaded onto a strong cation exchange cartridge in methanol. The cartridge was flushed with several volumes of methanol which were discarded. The product was eluted with 2 M ammonia in methanol and concentrated to give 20.6 mg (98%) as a colorless film. 1H-NMR (CDCl3, 500 MHz) δ 7.98 (s, 1H), 7.86 (s, 1H), 7.35 (m, 2H), 7.23 (s, 1H), 7.00 (m, 2H), 4.82 (s, 2H), 4.21 (s, 3H), 3.54 (s, 2H), 2.90 (m, 2H), 2.74 (m, 2H), 2.14 (m, 2H), 1.60-2.05 (m, 3H); 13C-NMR (CDCl3, 126 MHz) δ 162.3, 160.3, 147.6, 140.2, 129.2, 128.9, 128.8, 125.6, 124.9 (q, J=272 Hz), 124.2 (q, J=32 Hz), 120.8, 118.8 (q, J=2.9 Hz), 117.6 (q, J=5.8 Hz), 115.0, 114.9, 79.9, 68.7, 42.7, 41.6, 40.7, 33.9. Mass spec.: 422.12 (MH)+. Accurate mass spec.: m/z 422.1836 [MH]+, Δ=4.6 ppm.
Cn1cc2cc(C(F)(F)F)cc(COCC3(c4ccc(F)cc4)CCNCC3)c2n1
null
Cn1cc2cc(C(F)(F)F)cc(COCC3(c4ccc(F)cc4)CCN(C(=O)OC(C)(C)C)CC3)c2n1
null
null
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:21][O:22][CH2:23][C:24]3[C:32]4[C:28](=[CH:29][N:30]([CH3:33])[N:31]=4)[CH:27]=[C:26]([C:34]([F:37])([F:36])[F:35])[CH:25]=3)[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1>FC(F)(F)C(O)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:21][O:22][CH2:23][C:24]3[C:32]4[C:28](=[CH:29][N:30]([CH3:33])[N:31]=4)[CH:27]=[C:26]([C:34]([F:35])([F:36])[F:37])[CH:25]=3)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1
0.25
O=C(O)C(F)(F)F
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
1,689,588
null
null
null
null
ord_dataset-c1e70ad912eb438f8d34b1dc681f809a
2016-01-01T00:02:00
true
4-(3,5-Dimethylisoxazol-4-yl)-N1-ethyl-6-(6-methylquinolin-5-yl)benzene-1,2-diamine (90 mg, 0.24 mmol) and 1,1′-carbonyldiimidazole (86.2 mg, 0.53 mmol) were added to tetrahydrofuran (10 ml) in a sealed vessel and heated to 105° C. overnight. The reaction mixture was the diluted in EtOAc and aqueous ammonium chloride and extracted with EtOAc (3 times). Organics were washed with ammonium chloride, water and brine and dried over sodium sulfate. Solvent was evaporated to dryness Crude material was purified by silica gel chromatography (DCM/MeOH as eluent) then by preparative HPLC to afford 5-(3,5-dimethylisoxazol-4-yl)-1-ethyl-7-(6-methylquinolin-5-yl)-1H-benzo[d]imidazol-2(3H)-one.
CCn1c(=O)[nH]c2cc(-c3c(C)noc3C)cc(-c3c(C)ccc4ncccc34)c21
null
O=C(n1ccnc1)n1ccnc1
CCNc1c(N)cc(-c2c(C)noc2C)cc1-c1c(C)ccc2ncccc12
null
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]([NH2:27])[C:10]([NH:24][CH2:25][CH3:26])=[C:11]([C:13]3[C:22]([CH3:23])=[CH:21][CH:20]=[C:19]4[C:14]=3[CH:15]=[CH:16][CH:17]=[N:18]4)[CH:12]=2)=[C:5]([CH3:28])[O:4][N:3]=1.[C:29](N1C=CN=C1)(N1C=CN=C1)=[O:30].O1CCCC1>CCOC(C)=O>[CH3:1][C:2]1[C:6]([C:7]2[CH:12]=[C:11]([C:13]3[C:22]([CH3:23])=[CH:21][CH:20]=[C:19]4[C:14]=3[CH:15]=[CH:16][CH:17]=[N:18]4)[C:10]3[N:24]([CH2:25][CH3:26])[C:29](=[O:30])[NH:27][C:9]=3[CH:8]=2)=[C:5]([CH3:28])[O:4][N:3]=1
null
CCOC(C)=O
C1CCOC1
null
105
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
805,589
null
null
null
null
ord_dataset-ed846b4b229e4bb09ad9dba95ad7ebeb
2008-01-01T00:01:00
true
Example 63 was prepared using the same procedure as described for example 4, starting from N-BOC-(R)-2-(3-bromo-4-hydroxybenzyl)morpholine, example 4, intermediate (a), and 1-iodopropane. The resulting intermediate was deprotected with TFA as described for example 4 to yield the desired morpholine example 63 as a colorless oil (27 mg, 64% over 2 steps) after purification by HPLC.
CCCOc1ccc(C[C@@H]2CNCCO2)cc1Br
null
CC(C)(C)OC(=O)N1CCO[C@H](Cc2ccc(O)c(Br)c2)C1
CC(C)(C)OC(=O)N1CCO[C@H](Cc2cccc(C=Cc3cccnc3)c2)C1
null
C([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([Br:22])[CH:16]=2)[CH2:9]1)(OC(C)(C)C)=O.C(N1CCO[C@H](CC2C=CC=C(C=CC3C=NC=CC=3)C=2)C1)(O[C:26](C)([CH3:28])[CH3:27])=O.ICCC.C(O)(C(F)(F)F)=O>>[Br:22][C:17]1[CH:16]=[C:15]([CH:20]=[CH:19][C:18]=1[O:21][CH2:27][CH2:26][CH3:28])[CH2:14][C@H:10]1[O:11][CH2:12][CH2:13][NH:8][CH2:9]1
null
O=C(O)C(F)(F)F
CCCI
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
960,192
null
null
null
null
ord_dataset-ed65749688da45af8a8432967b017729
2010-01-01T00:05:00
true
61.2 Using general method A, (3-amino-[1,2,4]triazol-1-yl)-acetic acid ethyl ester was coupled with 5-chlorothiophene-2-carboxylic acid to give {3-[(5-chloro-thiophene-2-carbonyl)-amino]-[1,2,4]triazol-1-yl}-acetic acid ethyl ester. Off-white solid. MS 315.1 ([M+H]+)
CCOC(=O)Cn1cnc(NC(=O)c2ccc(Cl)s2)n1
null
O=C(O)c1ccc(Cl)s1
CCOC(=O)Cn1cnc(N)n1
null
[CH2:1]([O:3][C:4](=[O:12])[CH2:5][N:6]1[CH:10]=[N:9][C:8]([NH2:11])=[N:7]1)[CH3:2].[Cl:13][C:14]1[S:18][C:17]([C:19](O)=[O:20])=[CH:16][CH:15]=1>>[CH2:1]([O:3][C:4](=[O:12])[CH2:5][N:6]1[CH:10]=[N:9][C:8]([NH:11][C:19]([C:17]2[S:18][C:14]([Cl:13])=[CH:15][CH:16]=2)=[O:20])=[N:7]1)[CH3:2]
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
1,352,067
[Pd]
null
null
null
ord_dataset-6034127657614f02860ed057b62b882e
2013-01-01T00:10:00
true
The mixture of tert-butyl 2-chloropyridin-3-ylcarbamate (10.0 g), 4-nitroaniline (8.0 g), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (2.53 g), Pd2(dba)3 (2 g) and sodium tert-butoxide (12.5 g) in toluene (160 mL)-2-propanol (40.0 mL) was stirred at 100° C. under Ar overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 0%-100% EtOAc in hexane) to give 3-(4-nitrophenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (4.0 g) as a light brown solid. A mixture of 3-(4-nitrophenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (3.50 g), sodium hydride (0.400 g) and iodoethane (2.0 mL) in DMF (40 mL) was stirred at 20° C. under a dry atmosphere (CaCl2 tube) for 1 h. The mixture was concentrated under reduced pressure. The residue was purified by column chromatography (NH silica gel, eluted with 0%-30% EtOAc in hexane) to give 1-ethyl-3-(4-nitrophenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (2.70 g) as a brown solid. A mixture of 1-ethyl-3-(4-nitrophenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (2.70 g) and 10% palladium-carbon (0.832 g) in EtOH (250 mL) was hydrogenated under balloon pressure at room temperature for 3 h. The catalyst was removed by filtration and the filtrate was concentrated in vacuo to give 3-(4-aminophenyl)-1-ethyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (1.00 g) as a brown solid.
CCn1c(=O)n(-c2ccc(N)cc2)c2ncccc21
null
CCn1c(=O)n(-c2ccc([N+](=O)[O-])cc2)c2ncccc21
null
null
[CH2:1]([N:3]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-])=O)=[CH:14][CH:13]=2)[C:4]1=[O:21])[CH3:2]>CCO.[C].[Pd]>[NH2:18][C:15]1[CH:14]=[CH:13][C:12]([N:5]2[C:6]3=[N:7][CH:8]=[CH:9][CH:10]=[C:11]3[N:3]([CH2:1][CH3:2])[C:4]2=[O:21])=[CH:17][CH:16]=1
3
CCO
null
null
null
null
41.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
204,898
null
null
null
null
ord_dataset-72fffaae67c8473fb9d951cb1b026646
1990-01-01T00:03:00
true
A solution of 2.87 g (=0.015 mol) thiophene-2-sulfonyl chloride in 20 ml dichloromethane was added dropwise with ice cooling to a solution of 3.5 g (=0.014 mol) 7-benzyl-9,9-dimethyl-3,7-diazabicyclo[3,3,1]nonane (=substance No. C8 in the following Table C) in 40 ml dichloromethane. Then the ice bath was removed and the reaction mixture stirred further for 3 hours at room temperature. The reaction mixture was then made alkaline by adding aqueous sodium hydroxide solution, the aqueous phase was separated and extracted twice with dichloromethane. The combined dichloromethane phases were dried over magnesium sulfate and the solvent was evaporated. 4.0 g of the title compound (base) were thereby obtained as an oil.
CC1(C)C2CN(Cc3ccccc3)CC1CN(S(=O)(=O)c1cccs1)C2
null
CC1(C)C2CNCC1CN(Cc1ccccc1)C2
O=S(=O)(Cl)c1cccs1
null
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6](Cl)(=[O:8])=[O:7].[CH2:10]([N:17]1[CH2:24][CH:23]2[C:25]([CH3:27])([CH3:26])[CH:19]([CH2:20][NH:21][CH2:22]2)[CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>ClCCl>[CH2:10]([N:17]1[CH2:18][CH:19]2[C:25]([CH3:27])([CH3:26])[CH:23]([CH2:22][N:21]([S:6]([C:2]3[S:1][CH:5]=[CH:4][CH:3]=3)(=[O:8])=[O:7])[CH2:20]2)[CH2:24]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
3
ClCCl
null
null
25
null
73.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
961,255
[Na+]
null
null
null
ord_dataset-ed65749688da45af8a8432967b017729
2010-01-01T00:05:00
true
1 g of (E)-3-(dimethylamino)-1-imidazo[1,2-a]pyridin-3-yl-2-propen-1-one [1-2] was dissolved in 10 mL of n-butanol, then 354 mg of thiourea and 377 mg of sodium methoxide were added, and the mixture was stirred at 85° C. for 2 hours. After cooling back to the room temperature, 868 μL of methyl iodide was added, and stirred at room temperature for 30 minutes. The solvent was distilled off until the volume is halved, the solid thus produced was taken and washed with diethyl ether and with water in the subsequent order, and then dried under reduced pressure to obtain 728 mg of 3-[2-methylthio-4-pyrimidinyl]imidazo[1,2-a]pyridine [1-3] as a grey solid.
CSc1nccc(-c2cnc3ccccn23)n1
null
NC(N)=S
C[O-]
CN(C)/C=C/C(=O)c1cnc2ccccn12
CN(C)/[CH:3]=[CH:4]/[C:5]([C:7]1[N:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]2=[N:9][CH:8]=1)=O.[NH2:17][C:18]([NH2:20])=[S:19].[CH3:21][O-].[Na+].CI>C(O)CCC>[CH3:21][S:19][C:18]1[N:20]=[C:5]([C:7]2[N:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]3=[N:9][CH:8]=2)[CH:4]=[CH:3][N:17]=1
2
CI
CCCCO
null
85
64.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
461,538
Cl
null
null
null
ord_dataset-5ca9db262dd24c5a9315cdc8ef055b7e
2000-01-01T00:04:00
true
To a cooled (0° C.) stirred suspension of 3-amino-3-(3',4'-dimethoxyphenyl)propionate hydrochloride (1.38 grams, 5.0 mmol) and triethylamine (1.5 milliliters , 10.8 mmol) in 20 milliliters of tetrahydrofuran was added nicotinoyl chloride hydrochloride (0.89 grams, 5.0 mmol). The thick slurry was stirred for 15 minutes and then allowed to warm to room temperature and stirring was continued for 2 hours. The reaction mixture was treated with 20 milliliters of water resulting in a brown colored solution. The tetrahydrofuran was removed in vacuo and the aqueous layer was extracted with methylene chloride (3 times, milliliters). The combined extracts were dried over magnesium sulfate and concentrated in vacuo to afford an oil which solidified overnight. The white solid was dried in vacuo (60° C., <1 mm) to afford 0.52 grams (30%) of crude product. The crude product was purified by flash chromatography (silica gel, 5% methanol/methylene chloride) and dried in vacuo (60° C., <1 mm) to afford 0.38 grams (22%) of the product as a white solid: 1H NMR (CDCl3) δ 9.10-9.00(m , 1 H), 8.80-8.69(m , 1 H), 8.19-8.08(m , 1 H), 7.65-7.31(m, 2 H), 6.96-6.76(m, 3 H), 5.64-5.50(m, 1 H), 3.87(s, 3 H), 3.67(s, 3 H), 3.14-2.37(m, 2 H). 13C NMR (CDCl3) δ 6 172.1, 164.6, 152.4, 149.2, 148.7, 148.1, 135.0, 132.8, 129.9, 123.5, 118.1, 111.3, 111.2, 109.9, 109.8, 55.9, 52.0, 49.8, 39.5. HPLC 99.47%.
COC(=O)CC(NC(=O)c1cccnc1)c1ccc(OC)c(OC)c1
null
COc1ccc(C(N)CC(=O)O)cc1OC
O=C(Cl)c1cccnc1
CCN(CC)CC
Cl.[NH2:2][CH:3]([C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=1)[CH2:4][C:5]([OH:7])=[O:6].[CH2:18](N(CC)CC)C.Cl.[C:26](Cl)(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[N:29][CH:28]=1.O>O1CCCC1>[C:26]([NH:2][CH:3]([C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=1)[CH2:4][C:5]([O:7][CH3:18])=[O:6])(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[N:29][CH:28]=1
2
C1CCOC1
O
null
0
22.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,046,631
null
null
null
null
ord_dataset-dd320ded4b3f4764af39de99491533f7
2011-01-01T00:04:00
true
3-(1-Bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutanone (51.988 g, 0.17 mot) in anhydrous THF (550 g, 620 mL) under nitrogen at −78° C. was treated with a 3.0 M solution of methyl magnesium chloride in THF (130 mL, 0.38 mol) over 30 min. The mixture was stirred at −78° C. for 30 min and then the cooling bath was removed and the mixture quenched with 14% NH4Cl (132 g). EtOAc was added to the aqueous phase and the pH was adjusted to ˜5 with 20% HCl and the layers separated. The combined organic phases were concentrated in vacuo to a slurry and 0.5 L of toluene was added and the mixture concentrated in vacuo until the EtOAc was removed. The slurry was heated at reflux until homogeneous then allowed to coot to provide desired product, which was isolated by filtration and dried in vacuo. 1H NMR (DMSO-d6, 400 MHz): δ 1.37 (s, 3H), 2.35-2.49 (m, 4H), 3.52 (dddd, 1H, J=9.6, 9.6, 9.6, 9.6 Hz), 5.18 (bs, 1H), 7.37 (d, 1H, J=5.2 Hz) and 8.26 (d, 1H, J=5.2 Hz).
CC1(O)CC(c2nc(Br)c3c(Cl)nccn23)C1
null
O=C1CC(c2nc(Br)c3c(Cl)nccn23)C1
C[Mg]Cl
null
[Br:1][C:2]1[N:3]=[C:4]([CH:12]2[CH2:15][C:14](=[O:16])[CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([Cl:11])[C:6]=12.[CH3:17][Mg]Cl>C1COCC1>[Br:1][C:2]1[N:3]=[C:4]([CH:12]2[CH2:13][C:14]([CH3:17])([OH:16])[CH2:15]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([Cl:11])[C:6]=12
0.5
C1CCOC1
null
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
1,554,911
C[Si](C)(C)I
null
null
null
ord_dataset-4e54080057a44c3887653391e24c90b6
2015-01-01T00:03:00
true
To a suspension of 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6′-methoxy-3,4,4′-trimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (17 mg, 0.036 mmol) in CH3CN (0.7 mL) was added TMSI (10 uL, 0.072 mmol) dropwise at 20° C. The reaction was stirred at 50° C. for 30 min. Additional TMSI (10 uL, 0.072 mmol) was added and the reaction was heated at 50° C. for 2 h. Additional TMSI (10 uL, 0.072 mmol) was added and the reaction was heated at 70° C. for 2 h. MeOH (1.0 mL) was added and the solution was re-partitioned between EtOAc and H2O. The organic layer was washed with NaHSO3 (2×), brine, dried over MgSO4 and evaporated to dryness to yield a white solid that was further purified by preparative TLC (10% MeOH-EtOAc) to yield 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6′-hydroxy-3,4,4′-trimethyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (8 mg, 49%). 1H NMR (400 MHz, MeOD) 7.92 (s, 1H), 7.28 (d, J=1.6 Hz, 1H), 7.22 (dd, J=1.7, 8.3 Hz, 1H), 7.14-7.10 (m, 2H), 6.36 (s, 1H), 2.27 (s, 3H), 1.95 (s, 3H), 1.81 (d, J=0.6 Hz, 3H), 1.56 (dd, J=3.9, 7.0 Hz, 2H), 1.14 (dd, J=3.9, 7.0 Hz, 2H). Retention time: 1.49 min; ESI-MS m/z calc. 453.4. found 454.2 (M+H)+.
Cc1cc(O)ncc1-c1nc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)cc(C)c1C
null
COc1cc(C)c(-c2nc(NC(=O)C3(c4ccc5c(c4)OC(F)(F)O5)CC3)cc(C)c2C)cn1
null
null
[F:1][C:2]1([F:34])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[CH:24]=[N:25][C:26]([O:30]C)=[CH:27][C:28]=5[CH3:29])[C:20]([CH3:32])=[C:19]([CH3:33])[CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.[Si](I)(C)(C)C.CO>CC#N>[F:34][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[CH:24]=[N:25][C:26]([OH:30])=[CH:27][C:28]=5[CH3:29])[C:20]([CH3:32])=[C:19]([CH3:33])[CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1
0.5
CO
CC#N
null
50
null
49
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
428,489
[Na+]
[OH-]
null
null
ord_dataset-8cce6f317d644b348a7978a2dce3ea01
1999-01-01T00:03:00
true
2 b) The ester from 2 a) was hydrolyzed in accordance with a standard method (sodium hydroxide in methanol). E-3-[4-(3-Dimethylamino-propoxy)phenyl)-2-methyl-propenoic acid was isolated.
C/C(=C\c1ccc(OCCCN(C)C)cc1)C(=O)O
null
CCOC(=O)/C(C)=C/c1ccc(OCCCN(C)C)cc1
null
null
[CH3:1][N:2]([CH3:21])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10](/[CH:13]=[C:14](\[CH3:20])/[C:15]([O:17]CC)=[O:16])=[CH:9][CH:8]=1.[OH-].[Na+]>CO>[CH3:21][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10](/[CH:13]=[C:14](\[CH3:20])/[C:15]([OH:17])=[O:16])=[CH:11][CH:12]=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
599,227
Cl
null
null
null
ord_dataset-82e842e611ef4a05b6e7f9ea0a46d52d
2003-01-01T00:07:00
true
To a solution of 6-bromo-7-methyl-1-naphthalen-2-ylmethyl-1,3-dihydro-indol-2-one (495.7 mg, 1.36 mmol) in THF (30 ml) was added 4-picolyl chloride hydrochloride (893 mg, 5.45 mmol). The resulting suspension was purged with nitrogen gas for 10 minutes, after which time an aqueous potassium hydroxide (1N, 10.88 ml, degassed for 10 minutes prior to the addition) was added dropwise at room temperature. The dark solution was stirred at room temperature overnight. After removal of THF, the reaction mixture was partitioned between water and ethyl ether. The organic layer was dried over MgSO4, filtered and concentrated under vacuum to give the crude product. It was chromatographed on flash silica gel eluting with ethyl acetate to provide the title compound of 2D (524 mg, 0.956 mmol, 70.3% yield).
Cc1c(Br)ccc2c1N(Cc1ccc3ccccc3c1)C(=O)C2(Cc1ccncc1)Cc1ccncc1
null
ClCc1ccncc1
Cc1c(Br)ccc2c1N(Cc1ccc3ccccc3c1)C(=O)C2
null
[Br:1][C:2]1[C:10]([CH3:11])=[C:9]2[C:5]([CH2:6][C:7](=[O:23])[N:8]2[CH2:12][C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:14]=2)=[CH:4][CH:3]=1.Cl.[N:25]1[CH:30]=[CH:29][C:28]([CH2:31]Cl)=[CH:27][CH:26]=1>C1COCC1>[Br:1][C:2]1[C:10]([CH3:11])=[C:9]2[C:5]([C:6]([CH2:31][C:28]3[CH:29]=[CH:30][N:25]=[CH:26][CH:27]=3)([CH2:31][C:28]3[CH:29]=[CH:30][N:25]=[CH:26][CH:27]=3)[C:7](=[O:23])[N:8]2[CH2:12][C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:14]=2)=[CH:4][CH:3]=1
8
C1CCOC1
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
983,268
O=C([O-])[O-]
[K+]
null
null
ord_dataset-35b56288528641309a040cc2b6710b61
2010-01-01T00:08:00
true
2-(4-aminophenyl)-1-cyclopropyl-6-hydroxyindole-3-carbonitrile (0.29 g, 1.0 mmol), prepared in example 1DD, step A, is mixed with K2CO3 (0.35 g, 2.5 mmol), toluene-4-sulfonic acid tetrahydrofuran-2-yl ester (0.36 g, 1.5 mmol) and acetonitrile (5 mL) and the mixture is stirred at 80° C. overnight. The solvent is removed in vacuum and the residue is treated with DCM and chromatographed (silica gel, DCM/EtOAc, 9/1) to provide 2-(4-aminophenyl)-1-cyclopropyl-6-(tetrahydrofuran-2-yloxy)indole-3-carbonitrile (0.27 g, 75%).
N#Cc1c(-c2ccc(N)cc2)n(C2CC2)c2cc(OC3CCCO3)ccc12
null
Cc1ccc(S(=O)(=O)OC2CCCO2)cc1
N#Cc1c(-c2ccc(N)cc2)n(C2CC2)c2cc(O)ccc12
null
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:20]3[CH2:22][CH2:21]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([OH:19])[CH:11]=3)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[O:29]1[CH2:33][CH2:32][CH2:31][CH:30]1OS(C1C=CC(C)=CC=1)(=O)=O>C(#N)C>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:20]3[CH2:21][CH2:22]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][CH:30]2[CH2:31][CH2:32][CH2:33][O:29]2)[CH:11]=3)=[CH:4][CH:3]=1
8
CC#N
null
null
80
null
75.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,051,505
null
null
null
null
ord_dataset-373415d3e0e54004837cf4831e67666f
2011-01-01T00:05:00
true
A mixture of 10-bromo-2-methanesulfinyl-5H,7H-benzo[b]pyrimido[4,5-d]azepin-6-one (100 mg) was stirred with N-methyl aniline (1 mL) and refluxed overnight at 150° C. Water was added and the product was extracted with methylene chloride, dried over MgSO4, filtered and concentrated. Purification by C-18 RP LC-MS chromatography afforded I-85 (10%): MS m/z=395 (M+H).
CN(c1ccccc1)c1ncc2c(n1)-c1cc(Br)ccc1NC(=O)C2
null
CS(=O)c1ncc2c(n1)-c1cc(Br)ccc1NC(=O)C2
CNc1ccccc1
null
[Br:1][C:2]1[CH:20]=[CH:19][C:5]2[NH:6][C:7](=[O:18])[CH2:8][C:9]3[CH:14]=[N:13][C:12](S(C)=O)=[N:11][C:10]=3[C:4]=2[CH:3]=1.[CH3:21][NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>O>[Br:1][C:2]1[CH:20]=[CH:19][C:5]2[NH:6][C:7](=[O:18])[CH2:8][C:9]3[CH:14]=[N:13][C:12]([N:22]([CH3:21])[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[N:11][C:10]=3[C:4]=2[CH:3]=1
null
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
1,254,196
[K+]
[OH-]
null
null
ord_dataset-c544c0c663f54dbea4ddb52ddde7934e
2013-01-01T00:01:00
true
To a solution of 2-fluoro-5-nitro-6-picoline (5.0 g, 32 mmol) and 2-mercaptoethanol (4.5 ml, 64 mmol), KOH (2 g, 36 mmol) was added at 0° C. The mixture was stirred at the same temperature for 15 minutes. The crude mixture was extracted with AcOEt and brine. Organic phase was dried over MgSO4, filtered, and concentrated to provide the crude 2-(6-methyl-5-nitro-pyridin-2-ylsulfanyl)-ethanol as an oil (7.238 g). 1HNMR (DMSO-d4, 400 MHz) δ 2.75 (s, 3H), 3.30-3.33 (m, 2H), 3.63-3.67 (m, 2H), 4.65-4.68 (m, 1H), 7.40-7.43 (m, 1H), 8.24-8.26 (m, 1H). Exact mass calculated for C8H10N2O3S 214.04 found 215.1 (MH+).
Cc1nc(SCCO)ccc1[N+](=O)[O-]
null
OCCS
Cc1nc(F)ccc1[N+](=O)[O-]
null
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([CH3:11])[N:3]=1.[SH:12][CH2:13][CH2:14][OH:15].[OH-].[K+]>>[CH3:11][C:4]1[N:3]=[C:2]([S:12][CH2:13][CH2:14][OH:15])[CH:7]=[CH:6][C:5]=1[N+:8]([O-:10])=[O:9]
0.25
null
null
null
null
null
105.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,457,952
[Na+]
[OH-]
null
null
ord_dataset-a86112d52cd54525a5e36d41f18aced2
2014-01-01T00:07:00
true
To a solution of methyl 2-[2-phenyl-4-p-tolyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-b]pyridin-3-yl]pentanoate (0.194 g; 0.42 mmol) in methanol (4.2 mL) was added a solution of sodium hydroxide 10 N (0.42 ml) and the mixture was heated to 60° C. for 18 h. After cooling, the reaction mixture was concentrated under reduced pressure and the crude solid was suspended in ethyl acetate and the mixture was acidified with 1N HCl (pH˜2). The organic layer was washed with brine, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by preparative thin layer chromatography silica using a mixture ethyl acetate/heptane (1/1)+0.5% acetic acid as eluent to afford 0.072 g (39%) of the title compound as a white solid.
CCCC(C(=O)O)c1c(-c2ccccc2)nc2sc3c(c2c1-c1ccc(C)cc1)CCC3
null
CCCC(C(=O)OC)c1c(-c2ccccc2)nc2sc3c(c2c1-c1ccc(C)cc1)CCC3
null
null
[C:1]1([C:7]2[N:12]=[C:11]3[S:13][C:14]4[CH2:18][CH2:17][CH2:16][C:15]=4[C:10]3=[C:9]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)[C:8]=2[CH:26]([CH2:31][CH2:32][CH3:33])[C:27]([O:29]C)=[O:28])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+]>CO>[C:1]1([C:7]2[N:12]=[C:11]3[S:13][C:14]4[CH2:18][CH2:17][CH2:16][C:15]=4[C:10]3=[C:9]([C:19]3[CH:20]=[CH:21][C:22]([CH3:25])=[CH:23][CH:24]=3)[C:8]=2[CH:26]([CH2:31][CH2:32][CH3:33])[C:27]([OH:29])=[O:28])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
null
CO
null
null
60
null
38.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,017,144
O=C([O-])[O-]
[I-]
[K+]
null
ord_dataset-f024e9664ab64906a71a2ff6004cb3d0
2010-01-01T00:12:00
true
2.87 g (19.8 mmol) of 1-chloromethyl-3-fluoro-benzene in 5 ml of dry dimethylformamide were added to a suspension of 4.66 g (19.6 mmol) of [2-(3-hydroxy-phenyl)-ethyl]-carbamic acid tert-butyl ester, 4 g of K2CO3 and 0.3 g of potassium iodide in 50 ml of dry dimethylformamide. The reaction was first stirred at room temperature overnight, then was heated up to 50° C. for 6 hours. After evaporation of the solvent, water was added to the residue and the product was extracted with ethyl acetate. 7 g of crude oil were obtained. Purification by flash chromatography using a mixture of ethyl acetate/hexane (1:9→2:8 gradient) gave 5.9 g (86% yield) of the title product as a colourless oil.
CC(C)(C)OC(=O)NCCc1cccc(OCc2cccc(F)c2)c1
null
CC(C)(C)OC(=O)NCCc1cccc(O)c1
Fc1cccc(CCl)c1
null
Cl[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[CH:4]=1.[C:10]([O:14][C:15](=[O:26])[NH:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([OH:25])[CH:20]=1)([CH3:13])([CH3:12])[CH3:11].C([O-])([O-])=O.[K+].[K+].[I-].[K+]>CN(C)C=O>[C:10]([O:14][C:15](=[O:26])[NH:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[CH:4]=2)[CH:20]=1)([CH3:13])([CH3:11])[CH3:12]
8
CN(C)C=O
null
null
25
null
87.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,058,220
COCCOC(=O)N=NC(=O)OCCOC
O=C(O)c1ccccc1
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
ord_dataset-373415d3e0e54004837cf4831e67666f
2011-01-01T00:05:00
true
After benzoic acid (300 mg, 2.46 mmol), triphenylphosphine (775 mg, 2.95 mmol), (2R,4R)-2,4-pentanediol (308 mg, 2.95 mmol), and THF (12 ml) were added to a 50 ml flask, azodicarboxylic acid bis(2-methoxyethyl) ester (691.1 mg, 2.95 mmol) dissolved in THF (6 mL) was added dropwise thereto at 20° C., and the reaction was allowed to proceed for one hour. Water (0.5 ml) was added, and concentration was carried out. Then, water (10 ml) was added to the solution, and extraction was carried out using diethyl ether (10 mL, ×2). Then, the organic layer was washed with water (10 ml) and saturated salt water (10 ml), and dehumidified with anhydrous magnesium sulfate. Subsequently, a crude product obtained by concentration was purified by column chromatography (silica gel, 40% ethyl acetate-hexane solution) to give (4S,2R)-4-benzoyloxypentane-2-ol as a colorless oily substance (379 mg, yield: 74%/benzoic acid).
C[C@@H](O)C[C@H](C)OC(=O)c1ccccc1
null
C[C@@H](O)C[C@@H](C)O
null
null
[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:29][C@@H:30](O)[CH2:31][C@H:32]([OH:34])[CH3:33].COCCOC(N=NC(OCCOC)=O)=O>C1COCC1.O>[C:1]([O:9][C@@H:30]([CH3:29])[CH2:31][C@H:32]([OH:34])[CH3:33])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
1
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
1,042,829
[Pd]
null
null
null
ord_dataset-3af92aec23dc4810b92eb0d8c60023ee
2011-01-01T00:03:00
true
After then dissolving 50 mg of the 3-benzyloxycarbonyl-8-(2-fluorophenyl)-7-oxo-3-azabicyclo[4.3.0]nonane in 30 ml of methanol, 100 mg of 10% palladium-carbon was added and the mixture was stirred for 4 days at room temperature under a hydrogen atmosphere (1 atm). The reaction mixture was filtered and the filtrate was distilled off under reduced pressure to obtain 62 mg of 8-(2-fluorophenyl)-7-oxo-3-azabicyclo[4.3.0]nonane.
O=C1C(c2ccccc2F)CC2CNCCC12
null
O=C1C(c2ccccc2F)CC2CN(C(=O)OCc3ccccc3)CCC12
null
null
C(OC([N:11]1[CH2:19][CH2:18][CH:17]2[CH:13]([CH2:14][CH:15]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])[C:16]2=[O:20])[CH2:12]1)=O)C1C=CC=CC=1>CO.[C].[Pd]>[F:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[CH:15]1[CH2:14][CH:13]2[CH:17]([CH2:18][CH2:19][NH:11][CH2:12]2)[C:16]1=[O:20]
96
CO
null
null
25
195.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
949,373
null
null
null
null
ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8
2010-01-01T00:04:00
true
A small screw cap test tube was charged with N-[4-(3-Hydroxymethylene-2-oxo-2,3-dihydro-1H-indole-6-carbonyl)-phenyl]-acetamide (as prepared in Example 29, 70 mg, 0.217 mmol) and THF (2 mL). To the resulting solution was added 3-aminophenol (28 mg, 0.257 mmol), and the mixture was stirred for 24 h at 65° C. Subsequently, the reaction mixture was cooled to room temperature and concentrated in vacuo. The solid residue was recrystallized with ˜5 mL of i-prOH affording the title compound in 76% yield (0.068 g, 0.1645 mmol).
CC(=O)Nc1ccc(C(=O)c2ccc3c(c2)NC(=O)C3=CNc2cccc(O)c2)cc1
null
Nc1cccc(O)c1
CC(=O)Nc1ccc(C(=O)c2ccc3c(c2)NC(=O)C3=CO)cc1
null
O[CH:2]=[C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([C:14]3[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:23])[CH3:22])=[CH:16][CH:15]=3)=[O:13])=[CH:9][CH:10]=2)[NH:5][C:4]1=[O:24].[NH2:25][C:26]1[CH:27]=[C:28]([OH:32])[CH:29]=[CH:30][CH:31]=1>C1COCC1>[OH:32][C:28]1[CH:27]=[C:26]([NH:25][CH:2]=[C:3]2[C:11]3[C:6](=[CH:7][C:8]([C:12]([C:14]4[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:23])[CH3:22])=[CH:16][CH:15]=4)=[O:13])=[CH:9][CH:10]=3)[NH:5][C:4]2=[O:24])[CH:31]=[CH:30][CH:29]=1
24
C1CCOC1
null
null
65
76
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,537,724
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
O=C([O-])[O-]
[Na+]
null
ord_dataset-8d5c200bca27407ab9febe7598e16458
2015-01-01T00:01:00
true
To a mixture of 7-(1-azidoethyl)-6-bromo-3-methyl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (0.10 g, 0.32 mmol) and 4-fluorophenylboronic acid (53 mg, 0.38 mmol) in 1,4-dioxane (2 mL) was added a 1M solution of sodium carbonate in water (0.38 mL, 0.38 mmol) and tetrakis(triphenylphosphine)palladium(0) (18 mg, 0.016 mmol). The reaction mixture was heated at 100° C. overnight. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with water, brine, dried over MgSO4, and concentrated. The crude mixture was purified on silica gel, eluting with 0 to 40% EtOAc in hexane, to give the desired product (69 mg, 66%). LCMS calculated for C15H13FN5OS (M+H)+: m/z=330.1. Found: 330.0.
Cc1csc2nc(C(C)N=[N+]=[N-])c(-c3ccc(F)cc3)c(=O)n12
null
Cc1csc2nc(C(C)N=[N+]=[N-])c(Br)c(=O)n12
OB(O)c1ccc(F)cc1
null
[N:1]([CH:4]([C:6]1[N:7]=[C:8]2[S:16][CH:15]=[C:14]([CH3:17])[N:9]2[C:10](=[O:13])[C:11]=1Br)[CH3:5])=[N+:2]=[N-:3].[F:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:1]([CH:4]([C:6]1[N:7]=[C:8]2[S:16][CH:15]=[C:14]([CH3:17])[N:9]2[C:10](=[O:13])[C:11]=1[C:22]1[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=1)[CH3:5])=[N+:2]=[N-:3]
null
C1COCCO1
O
CCOC(C)=O
100
65.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
968,684
null
null
null
null
ord_dataset-03ba810b7f464a06b5d8787af2e8b64e
2010-01-01T00:06:00
true
Using Method C with 100 mg (0.34 mmol) 2a and 86 mg (0.41 mmol) 1-tert-butoxycarbonyl-2-pyrrolyl boronic acid, 6 mg pure title compound were obtained. The filtrate was submitted to purification by preparative HPLC (eluent:AcOEt) and a fraction of 52 mg of a product containing 25% (LC-MS) of the desired compound was obtained. A second purification using a semi-preparative Supelco discovery C18 column (250×10 mm) (eluent: acetonitrile:H2O 9:1) led to 6 mg (4.1%) of pure title compound. Reaction time: 18 hours. 1H-NMR (DMSO), δ (ppm), J (Hz): 1.25 (s, 9H, t-Bu), 3.60 (s, 3H, CH3O(4′)), 3.72 (s, 6H, CH3O(3′+5′)), 6.33 (t, 1H, Hpyr 4′, J=3.30), 6.58-6.60 (m, 1H, Hpyr 3′ or 5′), 7.16 (s, 2H, Harom(2+6)), 7.42-7.44 (m, 1H, Hpyr 5′ or 3′), 8.04 (s, 1H, HP5), 8.12 (s, 1H, HP3), 9.53 (s, 1H, NHamine); MS, (C22H16N4O5), m/z: 427 [M++1, 100].
COc1cc(Nc2cncc(-c3cccn3C(=O)OC(C)(C)C)n2)cc(OC)c1OC
null
COc1cc(Nc2cncc(Cl)n2)cc(OC)c1OC
CC(C)(C)OC(=O)n1cccc1B(O)O
null
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:13][C:14]2[CH:19]=[N:18][CH:17]=[C:16](Cl)[N:15]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[C:21]([O:25][C:26]([N:28]1[CH:32]=[CH:31][CH:30]=[C:29]1B(O)O)=[O:27])([CH3:24])([CH3:23])[CH3:22]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:13][C:14]2[CH:19]=[N:18][CH:17]=[C:16]([C:29]3[N:28]([C:26]([O:25][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:27])[CH:32]=[CH:31][CH:30]=3)[N:15]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10]
null
null
null
null
null
4.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
277,766
null
null
null
null
ord_dataset-ad17798fcea64e26ba91604fca520090
1993-01-01T00:10:00
true
A solution of 14.6 g (37.38 mmol) of 3-(4-acetoxy-3,5-di-tert-butylphenyl)-l-(tetrahydropyran-2-yloxy)propane in 80 ml of anhydrous methanol is stirred together with 1 g of amberlyst 15 (H+ -form) for 2 hours at 45° C. and maintained at room temperature overnight. After dilution of the suspension with 100 ml of methanol, the catalyst is removed by filtration and the filtrate evaporated at reduced pressure leaving 11.53 g of crude product, which is purified by flashchromatography over silica gel with H/AcOEt 3:1 as the eluent. 6.96 g (61%) of 3-(4-acetoxy-3,5-di-tert-butylphenyl)propanol is isolated from the product-containing fractions as a faintly yellowish oil, which gradually crystallizes upon standing, m.p. 93°-95° C. (C19H30O3 ; F. W. 306.4).
CC(=O)Oc1c(C(C)(C)C)cc(CCCO)cc1C(C)(C)C
null
CC(=O)Oc1c(C(C)(C)C)cc(CCCOC2CCCCO2)cc1C(C)(C)C
null
null
[C:1]([O:4][C:5]1[C:10]([C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:9][C:8]([CH2:15][CH2:16][CH2:17][O:18]C2CCCCO2)=[CH:7][C:6]=1[C:25]([CH3:28])([CH3:27])[CH3:26])(=[O:3])[CH3:2]>CO>[C:1]([O:4][C:5]1[C:6]([C:25]([CH3:26])([CH3:27])[CH3:28])=[CH:7][C:8]([CH2:15][CH2:16][CH2:17][OH:18])=[CH:9][C:10]=1[C:11]([CH3:14])([CH3:13])[CH3:12])(=[O:3])[CH3:2]
null
CO
null
null
25
60.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,553,887
[Ni]
null
null
null
ord_dataset-4e54080057a44c3887653391e24c90b6
2015-01-01T00:03:00
true
A mixture of 4-(5-(prop-2-ynylthio)-4H-1,2,4-triazol-3-yl)pyridine (1.6 g, 7.4 mmol) and Raney Ni in ethanol (30 mL) was stirred at reflux for 8 h. The reaction mixture was then filtered through a Celite pad and the solution was concentrated to obtain the crude compound. The crude product was purified by column chromatography to give 4-(4H-1,2,4-triazol-3-yl)pyridine (0.4 g).
c1cc(-c2nnc[nH]2)ccn1
null
C#CCSc1nnc(-c2ccncc2)[nH]1
null
null
C(S[C:5]1[NH:6][C:7]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)=[N:8][N:9]=1)C#C>C(O)C.[Ni]>[N:9]1[N:8]=[C:7]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)[NH:6][CH:5]=1
null
CCO
null
null
null
37
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
917,432
O=C([O-])[O-]
[K+]
null
null
ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d
2009-01-01T00:11:00
true
Allyl bromide (2.10 ml, 24.8 mmol) was added in one portion to a suspension of potassium carbonate (4.40 g, 31.8 mmol) and tert-butyl[2-(4-hydroxyphenyl)ethyl]carbamate (Prepared according to Journal of Organic Chemistry 1999, 64, 1074, 5.00 g, 21.1 mmol) in acetonitrile (50 ml) at room temperature. The reaction was stirred for 12 hours and the solvent removed in vacuo. Diethyl ether (50 ml) and water (20 ml) were added and the organics separated, washed with water (20 ml), dried (magnesium sulphate) and the solvent removed in vacuo to yield a clear oil. The oil was purified by column chromatography on silica gel eluting with ethyl acetate:pentane (25/75 by volume) to furnish the title compound as a white solid, 3.80 g.
C=CCOc1ccc(CCNC(=O)OC(C)(C)C)cc1
null
CC(C)(C)OC(=O)NCCc1ccc(O)cc1
C=CCBr
null
[CH2:1](Br)[CH:2]=[CH2:3].C(=O)([O-])[O-].[K+].[K+].[C:11]([O:15][C:16](=[O:27])[NH:17][CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=1)([CH3:14])([CH3:13])[CH3:12]>C(#N)C>[C:11]([O:15][C:16](=[O:27])[NH:17][CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:3][CH:2]=[CH2:1])=[CH:22][CH:21]=1)([CH3:14])([CH3:12])[CH3:13]
12
CC#N
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null