original_index
int64
2
1.77M
agent_000
stringlengths
1
540
agent_001
stringlengths
1
852
agent_002
stringlengths
1
247
date_of_experiment
timestamp[ns]date
extracted_from_file
stringclasses
489 values
grant_date
timestamp[ns]date
1976-01-01 00:01:00
2016-01-01 00:09:00
is_mapped
bool
1 class
procedure_details
stringlengths
8
24.5k
product_000
stringlengths
1
484
product_001
stringlengths
1
208
reactant_000
stringlengths
1
902
reactant_001
stringlengths
1
902
reactant_002
stringlengths
1
285
rxn_str
stringlengths
87
6.12k
rxn_time
float64
0
2.16k
solvent_000
stringclasses
446 values
solvent_001
stringclasses
405 values
solvent_002
stringclasses
330 values
temperature
float64
-230
30.1k
yield_000
float64
0
90,205,156,600B
yield_001
float64
0
100M
agent_003
null
agent_004
null
agent_005
null
agent_006
null
agent_007
null
agent_008
null
agent_009
null
agent_010
null
agent_011
null
agent_012
null
agent_013
null
agent_014
null
agent_015
null
agent_016
null
solvent_003
null
solvent_004
null
solvent_005
null
solvent_006
null
solvent_007
null
solvent_008
null
solvent_009
null
solvent_010
null
1,449,190
CN(C)C(On1nnc2ccccc21)=[N+](C)C
F[B-](F)(F)F
null
null
ord_dataset-a86112d52cd54525a5e36d41f18aced2
2014-01-01T00:07:00
true
A solution of 4-iodo-3-methoxybenzoic acid (250 mg, 0.90 mmol) in anhydrous dimethylformamide (8 mL) was treated with N-ethyl-N,N-diisopropylamine (0.63 mL, 3.6 mmol) and TBTU (404 mg, 1.26 mmol). The mixture was then treated with 1-methylpiperidin-4-amine (0.160 ml, 1.26 mmol). The reaction was stirred at room temperature for 24 h. The reaction was diluted with water and the resulting precipitate was collected by filtration to afford the title compound (250 mg, 71% yield).
COc1cc(C(=O)NC2CCCCN2C)ccc1I
null
CCN(C(C)C)C(C)C
CN1CCC(N)CC1
COc1cc(C(=O)O)ccc1I
[I:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[O:11][CH3:12].C([N:15](C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:44][N:45]1[CH2:50][CH2:49][CH:48](N)[CH2:47][CH2:46]1>CN(C)C=O.O>[I:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:15][CH:46]2[CH2:47][CH2:48][CH2:49][CH2:50][N:45]2[CH3:44])=[O:8])=[CH:4][C:3]=1[O:11][CH3:12]
24
O
CN(C)C=O
null
25
74.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
871,348
O=C([O-])O
[Na+]
null
null
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
2009-01-01T00:03:00
true
To a solution of 4-chloro-5-(2-ethoxyethyl)-5H-pyrrolo[3,2-d]pyrimidine (90 mg) in 1-methyl-2-pyrrolidone (0.7 mL), 3-chloro-4-[(3-fluorobenzyl)oxy]aniline (151 mg) was added, and the mixture was heated to 140° C. and stirred for 7 hrs. The reaction mixture was allowed to cool to room temperature. The reaction mixture was diluted with 5% aqueous sodium hydrogen carbonate solution (20 mL) and extracted with ethyl acetate (25 mL×3). The organic layer washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (basic silica gel, eluent:ethyl acetate/methanol=10/0→8/2). The object fraction was concentrated under reduced pressure. The residue was recrystallized from diisopropyl ether, collected by filtration and dried under reduced pressure to give the title compound (90 mg) as pale-yellow needle crystals.
CCOCCn1ccc2ncnc(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)c21
null
Nc1ccc(OCc2cccc(F)c2)c(Cl)c1
CCOCCn1ccc2ncnc(Cl)c21
null
Cl[C:2]1[C:3]2[N:10]([CH2:11][CH2:12][O:13][CH2:14][CH3:15])[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:16][C:17]1[CH:18]=[C:19]([CH:21]=[CH:22][C:23]=1[O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=1)[NH2:20]>CN1CCCC1=O.C(=O)([O-])O.[Na+]>[Cl:16][C:17]1[CH:18]=[C:19]([NH:20][C:2]2[C:3]3[N:10]([CH2:11][CH2:12][O:13][CH2:14][CH3:15])[CH:9]=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:21]=[CH:22][C:23]=1[O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=1
7
CN1CCCC1=O
null
null
140
null
51.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,136,198
null
null
null
null
ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820
2012-01-01T00:02:00
true
To a solution of (S)-tert-butyl 5,6-di(nitrooxy)hexanoate (12.41 g, 42.155 mmol) in DCM (47 mL) cooled to 0° C. under N2, boron trifluoride diethyl ether complex (5.82 mL, 46.37 mmol) was added. The reaction mixture was stirred at 0° C. for 10 minutes and at rt for 3 hrs. The solution was washed with brine, the organic layer was separated, dried over sodium sulfate and concentrated under reduced pressure. The crude brown oil was used in the next step without further purification.
O=C(O)CCC[C@@H](CO[N+](=O)[O-])O[N+](=O)[O-]
null
CC(C)(C)OC(=O)CCC[C@@H](CO[N+](=O)[O-])O[N+](=O)[O-]
null
null
[N+:1]([O:4][C@H:5]([CH2:16][O:17][N+:18]([O-:20])=[O:19])[CH2:6][CH2:7][CH2:8][C:9]([O:11]C(C)(C)C)=[O:10])([O-:3])=[O:2]>C(Cl)Cl>[N+:1]([O:4][C@H:5]([CH2:16][O:17][N+:18]([O-:20])=[O:19])[CH2:6][CH2:7][CH2:8][C:9]([OH:11])=[O:10])([O-:3])=[O: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
895,212
Cl
null
null
null
ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded
2009-01-01T00:08:00
true
N,N-Dimethylaminoacetyl chloride hydrochloride (100 mg) was added portionwise to a stirred solution of N-(3-chloro-2-fluorophenyl)-6-methoxy-7-(piperidin-4-yloxy)quinazolin-4-amine dihydrochloride (250 mg, 0.57 mmol) and diisopropylethylamine (300 μl) in methylene chloride (25 ml) at 0° C. The reaction mixture was allowed to stir for 2 hours to room temperature. The reaction mixture was washed with saturated sodium bicarbonate solution (25 ml), dried (MgSO4), filtered and evaporated. The residues were purified by column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10), followed by methylene chloride/methanol (saturated with ammonia) (90/10). The fractions containing the desired product were combined and evaporated under vacuum to give the title product as a white foam (0.125 g, 45%); 1H NMR Spectrum: (DMSO d6) 1.50-1.65 (m, 1H); 1.65-1.80 (m, 1H); 1.95-2.15 (m, 2H); 2.25 (s, 6H); 3.10-3.50 (m, 4H); 3.75-4.05 (m, 2H); 3.95 (s, 3H); 4.90 (m, 1H); 7.30 (m, 1H); 7.35 (s, 1H); 7.40-7.60 (m, 2H); 7.85 (s, 1H); 8.40 (s, 1H); 9.65 (s, 1H); Mass Spectrum: (M+H)+ 488.
COc1cc2c(Nc3cccc(Cl)c3F)ncnc2cc1OC1CCN(C(=O)CN(C)C)CC1
null
COc1cc2c(Nc3cccc(Cl)c3F)ncnc2cc1OC1CCNCC1
CN(C)CC(=O)Cl
null
Cl.[CH3:2][N:3]([CH2:5][C:6](Cl)=[O:7])[CH3:4].Cl.Cl.[Cl:11][C:12]1[C:13]([F:38])=[C:14]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:31][CH:32]4[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]4)=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:15]=[CH:16][CH:17]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[Cl:11][C:12]1[C:13]([F:38])=[C:14]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:31][CH:32]4[CH2:37][CH2:36][N:35]([C:6](=[O:7])[CH2:5][N:3]([CH3:4])[CH3:2])[CH2:34][CH2:33]4)=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:15]=[CH:16][CH:17]=1
null
ClCCl
CCN(C(C)C)C(C)C
null
null
null
44.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
889,613
O=C([O-])O
[Na+]
null
null
ord_dataset-11068b1e475b4c5b82e56726ab0dddb7
2009-01-01T00:07:00
true
para-Toluene sulfonyl chloride (262 mg, 1.38 mmol) was added to a solution of 5-bromo-2-carboxypyridine (118 mg, 0.58 mmol) and pyridine (0.3 mL, 0.39 mmol) in tert-butanol (1 mL) and the mixture was stirred at 40° C. for 10 minutes and room temperature for 2 hours. Saturated sodium hydrogen carbonate solution (4 mL) was then added and the mixture was stirred for 5 minutes. Diethyl ether was next added and the bi-phasic mixture was stirred for a further 10 minutes. The organic layer was then separated, washed with brine, dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by column chromatography on silica gel, eluting with pentane:ethyl acetate, 100:0 to 80:20, afforded the title compound as a colourless solid in 73% yield, 110 mg.
CC(C)(C)OC(=O)c1ccc(Br)cn1
null
O=C(O)c1ccc(Br)cn1
Cc1ccc(S(=O)(=O)Cl)cc1
null
[C:1]1([CH3:11])[CH:6]=CC(S(Cl)(=O)=O)=C[CH:2]=1.[Br:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]([OH:21])=[O:20])=[N:17][CH:18]=1.N1C=CC=CC=1.C(=O)([O-])O.[Na+]>C(O)(C)(C)C.C(OCC)C>[C:1]([O:20][C:19]([C:16]1[CH:15]=[CH:14][C:13]([Br:12])=[CH:18][N:17]=1)=[O:21])([CH3:11])([CH3:6])[CH3:2]
2
c1ccncc1
CCOCC
CC(C)(C)O
40
73
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,288,790
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
null
null
null
ord_dataset-d5c54236ecd94d61aaa071461bcfc426
2013-01-01T00:04:00
true
A degassed solution of 40 mg of 11i, 45 mg of 5-tributylstannyl thiazole and 15 mg of Pd(PPh3)4 in 3 ml of toluene was heated at 110° C. during 5 hr. The reaction mixture was concentrated and the residue was chromatographed over silica gel, using a gradient of toluene/acetone as eluent. The isolated product was treated with diethyl ether, to provide 31 mg of 11l as white crystalline material; Mp: 254-255° C.; Rf 0.30 (heptane/acetone 1/1).
COc1cc2c(cc1-c1cncs1)-c1c(-c3cncs3)c3c(n1CC2)C(=O)N(C(C)(C)C)CCOC3
null
COc1cc2c(cc1Br)-c1c(-c3cncs3)c3c(n1CC2)C(=O)N(C(C)(C)C)CCOC3
CCCC[Sn](CCCC)(CCCC)c1cncs1
null
Br[C:2]1[C:3]([O:31][CH3:32])=[CH:4][C:5]2[CH2:6][CH2:7][N:8]3[C:14]4[C:15](=[O:25])[N:16]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:17][CH2:18][O:19][CH2:20][C:13]=4[C:12]([C:26]4[S:30][CH:29]=[N:28][CH:27]=4)=[C:9]3[C:10]=2[CH:11]=1.C([Sn](CCCC)(CCCC)[C:38]1[S:42][CH:41]=[N:40][CH:39]=1)CCC>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:21]([N:16]1[C:15](=[O:25])[C:14]2[N:8]3[CH2:7][CH2:6][C:5]4[CH:4]=[C:3]([O:31][CH3:32])[C:2]([C:38]5[S:42][CH:41]=[N:40][CH:39]=5)=[CH:11][C:10]=4[C:9]3=[C:12]([C:26]3[S:30][CH:29]=[N:28][CH:27]=3)[C:13]=2[CH2:20][O:19][CH2:18][CH2:17]1)([CH3:22])([CH3:24])[CH3:23]
null
Cc1ccccc1
null
null
null
76.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
879,188
CS(=O)(=O)Cl
null
null
null
ord_dataset-3592bd645cd143ee8274cd0d834ae581
2009-01-01T00:05:00
true
To a solution of 4-[4-(5-Methoxy-2-methylindol-1-yl)phenyl]but-3-yn-1-ol (60 mg, 0.19 mmol) in methylene chloride (1 mL) at 0° C. was added triethylamine (54 μL, 0.39 mmol) and methanesulfonylchloride (18 μL, 0.39 mmol). After the solution was stirred at 0° C. for 2 hours, pyrrolidine (163 μL, 1.95 mmol) was added and the reaction was allowed to warm to room temperature overnight. After the reaction was quenched with water, the organic layer was dried over MgSO4, and concentrated. The residue was purified by HPLC to give the desired indole (2.8 mg). LC-MS (C24H26N2O calc'd 358) m/z 359 (M+H); 1H NMR (300 MHz, CDCl3) δ 7.53 (d, J=8.4 Hz, 2H), 7.26 (d, J=8.4 Hz, 2H), 7.03 (d, J=2.4 Hz, 1H), 6.99 (d, J=9.0 Hz, 1H), 6.73 (dd, J=2.7, 9.0 Hz, 1H), 6.32 (s, 1H), 3.85 (s, 3H), 2.92-2.83 (m, 4H), 2.76 (m, 4H), 2.28 (s, 3H), 1.88 (m, 4H).
COc1ccc2c(c1)cc(C)n2-c1ccc(C#CCCN2CCCC2)cc1
null
COc1ccc2c(c1)cc(C)n2-c1ccc(C#CCCO)cc1
CCN(CC)CC
null
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12]1[CH:17]=[CH:16][C:15]([C:18]#[C:19][CH2:20][CH2:21]O)=[CH:14][CH:13]=1)[C:7]([CH3:23])=[CH:6]2.[CH2:24]([N:26](CC)[CH2:27][CH3:28])[CH3:25].CS(Cl)(=O)=O.N1CCCC1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12]1[CH:13]=[CH:14][C:15]([C:18]#[C:19][CH2:20][CH2:21][N:26]3[CH2:27][CH2:28][CH2:25][CH2:24]3)=[CH:16][CH:17]=1)[C:7]([CH3:23])=[CH:6]2
2
ClCCl
C1CCNC1
null
0
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
633,922
O=C([O-])O
[I-]
[Na+]
null
ord_dataset-de283386b8034acd99fba96d3c7d3227
2004-01-01T00:04:00
true
2-Chloro-5-[(2-chloroethyl)amino]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (Example 29c, 0.200 g), N-(3-aminopropyl)-imidazole (0.957 g), triethylamine (1.2 ml), sodium iodide (0.010 g) and tetrahydrofuran (4 ml) were heated together in a sealed tube at 80° C. for 24 h. The solution was cooled, poured into saturated aqueous sodium hydrogencarbonate solution and extracted into ethyl acetate. The extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified on silica gel (eluant 19:1:0.1 dichloromethane/methanol/ammonia) to afford the title compound as a gum (0.176 g).
O=C(NCC12CC3CC(CC(C3)C1)C2)c1cc(NCCNCCCn2ccnc2)ccc1Cl
null
NCCCn1ccnc1
O=C(NCC12CC3CC(CC(C3)C1)C2)c1cc(NCCCl)ccc1Cl
null
[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([NH:22][CH2:23][CH2:24]Cl)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:5].[NH2:26][CH2:27][CH2:28][CH2:29][N:30]1[CH:34]=[CH:33][N:32]=[CH:31]1.[I-].[Na+].C(=O)([O-])O.[Na+]>O1CCCC1.C(N(CC)CC)C>[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([NH:22][CH2:23][CH2:24][NH:26][CH2:27][CH2:28][CH2:29][N:30]2[CH:34]=[CH:33][N:32]=[CH:31]2)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:15][CH:14]3[CH2:16][CH:10]([CH2:11][CH:12]([CH2:13]3)[CH2:17]1)[CH2:9]2)=[O:5]
null
CCN(CC)CC
C1CCOC1
null
null
71.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
943,769
null
null
null
null
ord_dataset-ed680843f6d14f5c9901869b2a06b4a4
2010-01-01T00:03:00
true
Formic acid (1.76 ml) was added to acetic acid anhydride (0.91 ml) at 0° C. The solution was stirred for 10 min at this temperature. The reaction was heated under nitrogen to 55° C. for 2 h. The reaction mixture was cooled to 0° C. 4-Chloro-3-fluoroaniline (1.07 g) dissolved in THF (2 ml) was added and the reaction was stirred over night at RT. The solvent was evaporated in vacuo. The residue was dissolved in THF (4 ml). The solution was cooled to 0° C. and borane tetrahydrofuran complex 1M in THF (16.2 ml) was added slowly. Strong gas evolution was observed. The reaction was heated to reflux for 3 h, then cooled to 0° C. and MeOH (4 ml) was added dropwise. The reaction was stirred for 1 h and 1M aq HCl solution (6 ml) was added. The reaction was stirred over night at RT. The solvent was removed in vacuo and the pH of the aqueous layer was adjusted to 9 with 2N aq NaOH solution. The reaction mixture was extracted twice with diethyl ether and the combined organic layers were dried over sodium sulfate, filtered and the solvent was removed in vacuo to yield (4-chloro-3-fluoro-phenyl)-methyl-amine (1150 mg, 98%) as a light brown oil. 1HNMR (DMSO-d6, 300 MHz): δ 2.65 (d, J=5.1 Hz, 3H), 6.15 (d, J=5.1 Hz, 1H), 6.20 (dd, J=3.0 and J=8.4 Hz, 1H), 6.45 (dd, J=2.4 and 12.3 Hz, 1H), 7.18 (t, J=8.7 Hz, 1H).
CNc1ccc(Cl)c(F)c1
null
CC(=O)OC(C)=O
Nc1ccc(Cl)c(F)c1
null
C(O)=O.[C:4](OC(=O)C)(=O)C.[Cl:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][C:13]=1[F:19]>C1COCC1>[Cl:11][C:12]1[CH:18]=[CH:17][C:15]([NH:16][CH3:4])=[CH:14][C:13]=1[F:19]
0.17
O=CO
C1CCOC1
null
55
98
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,423,163
null
null
null
null
ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f
2014-01-01T00:04:00
true
To a melt of urea (6.07 g, 101 mmol) (bath temp 150° C.) was added methyl 3-(2-methoxyphenyl)-2-oxocyclopentanecarboxylate (5.3 g, 20.21 mmol) dropwise. After stirring overnight, the reaction was cooled to rt. Added MeOH (30 ml), and broke up the solid mass with a spatula and stirred for 1 h. Added water (600 ml), and stirred for 3 hr. The mixture was added to a Buchner funnel, and washed with water. Dried overnight in the vacuum oven (45° C.) to obtain 7-(2-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diol (4.03 g, 15.60 mmol, 77% yield) as a tan solid. LC-MS (M+H)+=259.1.
COc1ccccc1C1CCc2c(O)nc(O)nc21
null
NC(N)=O
COC(=O)C1CCC(c2ccccc2OC)C1=O
null
[NH2:1][C:2]([NH2:4])=[O:3].[CH3:5][O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH:13]1[CH2:17][CH2:16][CH:15]([C:18](OC)=[O:19])[C:14]1=O.CO>O>[CH3:5][O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH:13]1[C:14]2[N:1]=[C:2]([OH:3])[N:4]=[C:18]([OH:19])[C:15]=2[CH2:16][CH2:17]1
8
O
CO
null
25
null
77.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,187,907
CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
null
null
null
ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff
2012-01-01T00:07:00
true
To a solution of 1-(1-benzenesulfonyl-5-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-ethanol (1.34 g, 3.07 mmol) in dichloromethane (50 ml) was added Dess-Martin periodinane (2.6 g, 6.14 mmol) at 25° C. The reaction mixture was stirred at 25° C. for 1 h and then quenched with a saturated aqueous sodium bicarbonate solution (20 mL). The mixture was extracted with ethyl acetate (100 mL), washed with a saturated aqueous sodium bicarbonate solution (3×20 mL), brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. The residue was purified by flash column chromatography (silica gel from QingDao, 200-300 mesh, 50% dichloromethane/hexanes) to afford 1-(1-benzenesulfonyl-5-trifluoromethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-ethanone (1.33 g, 100%) as a light yellow solid: LC/MS m/e calcd for C21H19F3N2O3S [M+H]+ 437.46, observed 436.8.
O=C(CC1CCCC1)c1cc2cc(C(F)(F)F)cnc2n1S(=O)(=O)c1ccccc1
null
O=S(=O)(c1ccccc1)n1c(C(O)CC2CCCC2)cc2cc(C(F)(F)F)cnc21
null
null
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[CH:23]([OH:30])[CH2:24][CH:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:23](=[O:30])[CH2:24][CH:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
1
ClCCl
null
null
25
99.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
783,373
CCCC1O[C@@H]2C[C@H]3[C@@H]4CCC5=CC(=O)C=C[C@]5(C)[C@H]4[C@@H](O)C[C@]3(C)[C@]2(C(=O)CO)O1
null
null
null
ord_dataset-4ad5db8537994579bef51f16dd8bf0bd
2007-01-01T00:08:00
true
To the solution of budesonide (431 mg, 1.0 mmol) in DCM (4.5 mL) was added heaxdecyl chloroformate (655 μL, 2.0 mmol) and Et3N (512 μL, 3.7 mmol) at room temperature. After reaction mixture was stirred at room temperature over night, it was poured into water (20 mL) and DCM (10 mL); the aqueous phase was extracted with DCM (10 mL). The combined organic phases were washed with water (10 mL) and brine (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo to provide crude budesonide hexadecylcarbonate. The product was purified by chromatography, eluted with Hexane:AcOEt=9:1 to 3:1 to provide 432 mg of 1:1 mixture of epimers (originated from budesonide) (99.38 area % purity on HPLC). 1H NMR (CDCl3) δ 0.80-2.40 (m, 53H), 2.56 (dt, 1H, 13.1 and 4.6 Hz), 4.30 (t, 2H, 6.7 Hz), 4.5-5.2 (m, 7H), 6.00 (s, 1H), 6.26 (d, 1H, 10.1 Hz), 7.3 (d, 1H, 10.1 Hz). 13C NMR (CDCl3) δ 14.16, 14.18, 14.34, 17.10, 17.27, 17.39, 17.71, 21.21, 22.88, 25.81, 28.79, 29.41, 29.56, 29.70, 29.76, 29.87, 30.54, 31.19, 32.11, 33.08, 33.59, 34.23, 35.19, 37.28, 40.68, 40.98, 44.37, 46.08, 47.52, 50.00, 53.07, 55.39, 55.49, 68.98, 69.73, 69.83, 69.95, 70.04, 82.10, 83.38, 97.71, 98.58, 104.70, 108.51, 122.57, 127.91, 155.08, 156.85, 170.48, 170.59, 186.84, 186.88, 202.10 and 203.38. Mass spectrum (m/e) 699 (M+).
CCCCCCCCCCCCCCCCOC(=O)[O-]
null
O=C([O-])Cl
null
null
[CH3:1][CH2:2][CH2:3][CH:4]1[O:24][C@:23]2([C:25]([CH2:27][OH:28])=[O:26])[C@@H:6]([CH2:7][C@@H:8]3[C@:22]2([CH3:29])[CH2:21][C@H:20]([OH:30])[C@H:19]2[C@H:9]3[CH2:10][CH2:11][C:12]3[C@:18]2([CH3:31])[CH:17]=[CH:16][C:14](=[O:15])[CH:13]=3)[O:5]1.ClC([O-])=[O:34].CCN(CC)CC.O>C(Cl)Cl>[CH3:1][CH2:2][CH2:3][CH:4]1[O:24][C@:23]2([C:25]([CH2:27][OH:28])=[O:26])[C@@H:6]([CH2:7][C@@H:8]3[C@:22]2([CH3:29])[CH2:21][C@H:20]([OH:30])[C@H:19]2[C@H:9]3[CH2:10][CH2:11][C:12]3[C@:18]2([CH3:31])[CH:17]=[CH:16][C:14](=[O:15])[CH:13]=3)[O:5]1.[CH2:23]([O:24][C:4](=[O:5])[O-:34])[CH2:6][CH2:7][CH2:8][CH2:22][CH2:21][CH2:20][CH2:19][CH2:9][CH2:10][CH2:11][CH2:12][CH2:18][CH2:17][CH2:16][CH3:14]
null
CCN(CC)CC
ClCCl
O
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
908,770
Cl
[Na+]
[OH-]
null
ord_dataset-46d216f2c4374ef5b9df90427e2a4cd4
2009-01-01T00:09:00
true
Sodium hydroxide (2 mL, 2 mmol, 1.00 N solution) was added to a solution of 19B (0.467 g, 1.24 mmol) in tetrahydrofuran (2 mL) and methanol (1 mL). The reaction was heated at 80° C. for 1 h. Hydrochloric acid (1 N) was added and the reaction mixture was extracted with ethyl acetate (2×). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure to give 19C (0.411 g, 91%) as a pale yellow solid. LC-MS m/z: 362.4 (M+H)+.
O=C(O)/C=C/c1cc(F)cc(N(Cc2ccccc2)Cc2ccccc2)c1
null
COC(=O)/C=C/c1cc(F)cc(N(Cc2ccccc2)Cc2ccccc2)c1
null
null
[OH-].[Na+].[CH2:3]([N:10]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:11]1[CH:12]=[C:13](/[CH:18]=[CH:19]/[C:20]([O:22]C)=[O:21])[CH:14]=[C:15]([F:17])[CH:16]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl>O1CCCC1.CO>[CH2:24]([N:10]([CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C:11]1[CH:12]=[C:13](/[CH:18]=[CH:19]/[C:20]([OH:22])=[O:21])[CH:14]=[C:15]([F:17])[CH:16]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
null
CO
C1CCOC1
null
80
null
91.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
300,520
O=C([O-])[O-]
[K+]
null
null
ord_dataset-fb70ed83140e4f53a907d87192ad748c
1994-01-01T00:11:00
true
A mixture of 2-acetylamino-5-chlorothiazole (1.76 g), 5-mercapto-2-methyl-1,3,4-thiadiazole (1.3 g) and potassium carbonate (2.0 g) in N,N-dimethylformamide (40 ml) was heated at 120° C. for 4 hours with stirring. The reaction mixture was concentrated under reduced pressure and water was added to this residue. The mixture was extracted with a mixture of tetrahydrofuran and ethyl titrate (1:1), washed with aqueous saturated sodium chloride and dried over magnesium sulfate. The solvent was concentrated under reduced pressure to give solid. The solid was subjected to column chromatography on silica gel (silica gel 60, 70-230 mesh; Merck: 150 g) and eluted with a mixture of chloroform and methanol (10:1). The fractions containing the objective compound were combined and concentrated under reduced pressure to give 2-acetylamino-5-(2-methyl-l,3,4-thiadiazol-5-ylthio)thiazole (1.65 g, yield: 60.7%).
CC(=O)Nc1ncc(Sc2nnc(C)s2)s1
null
Cc1nnc(S)s1
CC(=O)Nc1ncc(Cl)s1
null
[C:1]([NH:4][C:5]1[S:6][C:7](Cl)=[CH:8][N:9]=1)(=[O:3])[CH3:2].[SH:11][C:12]1[S:16][C:15]([CH3:17])=[N:14][N:13]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[C:1]([NH:4][C:5]1[S:6][C:7]([S:11][C:12]2[S:16][C:15]([CH3:17])=[N:14][N:13]=2)=[CH:8][N:9]=1)(=[O:3])[CH3:2]
null
CN(C)C=O
null
null
120
null
61.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,758,108
[Na+]
[OH-]
null
null
ord_dataset-97eb2ab57fec4160922caae33b54d956
2016-01-01T00:08:00
true
2.0 g of tetraethyl 5,5′-(1,8-naphthyridine-2,7-diyl)diisophthalate was dissolved in 60 mL of mixed solvent of THF and MeOH (v/v=1:1), 20 mL of 2N NaOH aqueous solution was added. The mixture was stirred at room temperature overnight. After the organic phase was removed, the aqueous phase was acidified with dilute hydrochloric acid to give white precipitate, which was filtered and washed with water several times. Yield: 1.5 g, 94%. 1H NMR (300 MHz, DMSO-d6): δ 8.44 (d, 2H), 8.62 (s, 2H), 8.68 (d, 2H), 9.10 (s, 4H).
O=C(O)c1cc(C(=O)O)cc(-c2ccc3ccc(-c4cc(C(=O)O)cc(C(=O)O)c4)nc3n2)c1
null
CCOC(=O)c1cc(C(=O)OCC)cc(-c2ccc3ccc(-c4cc(C(=O)OCC)cc(C(=O)OCC)c4)nc3n2)c1
null
null
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[CH:12]=[C:13]([C:22]([O:24]CC)=[O:23])[CH:14]=[C:15]([CH:21]=3)[C:16]([O:18]CC)=[O:17])[N:9]=2)[CH:4]=[CH:3][C:2]=1[C:27]1[CH:28]=[C:29]([C:38]([O:40]CC)=[O:39])[CH:30]=[C:31]([CH:37]=1)[C:32]([O:34]CC)=[O:33]>C1COCC1.CO.[OH-].[Na+]>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[CH:21]=[C:15]([C:16]([OH:18])=[O:17])[CH:14]=[C:13]([CH:12]=3)[C:22]([OH:24])=[O:23])[N:9]=2)[CH:4]=[CH:3][C:2]=1[C:27]1[CH:37]=[C:31]([C:32]([OH:34])=[O:33])[CH:30]=[C:29]([CH:28]=1)[C:38]([OH:40])=[O:39]
8
CO
C1CCOC1
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
702,216
null
null
null
null
ord_dataset-c408dfed796e4354b61e312e67f7143f
2006-01-01T00:04:00
true
In 100 mL of acetone were dissolved 16.2 g of poly(p-hydroxystyrene) and isopropyl chloride. To this reaction mixture was added 1.8 g of triethylamine. This mixture was stirred at 50 to 55° C. for 5 hours. The resultant reaction mixture was transferred to 1,000 mL of water, and the upper layer was removed by decantation. The viscous resinous substance obtained was dissolved in 75 mL of acetone, and this solution was transferred to 500 mL of water. The rubbery resin precipitated was dried under vacuum. Thus, 15.4 g of poly(p-hydroxystyrene/p-isopropoxystyrene) was obtained as a white powder.
C=Cc1ccc(O)cc1
C=Cc1ccc(OC(C)C)cc1
C#Cc1ccc(O)cc1
CC(C)Cl
null
[CH:1]#[C:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.[CH:10](Cl)([CH3:12])[CH3:11].C(N(CC)CC)C.O>CC(C)=O>[OH:9][C:6]1[CH:7]=[CH:8][C:3]([CH:2]=[CH2:1])=[CH:4][CH:5]=1.[CH:10]([O:9][C:6]1[CH:7]=[CH:8][C:3]([CH:2]=[CH2:1])=[CH:4][CH:5]=1)([CH3:12])[CH3:11]
5
CCN(CC)CC
CC(C)=O
O
52.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,214,299
CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC
[OH-]
null
null
ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777
2012-01-01T00:10:00
true
The reaction was carried out under argon. (rac)-4-{2-[(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)sulfonyl]-4-cyanophenyl}-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxamide (740 mg, 1.18 mmol) was initially charged in dry THF (30 ml), methoxy-carbonylsulfamoyltriethylammonium hydroxide (Burgess reagent; 1.699 g, 7.13 mmol; 6 eq.) was added and the mixture was stirred at RT. After 75 min, HPLC control showed complete conversion. The reaction mixture was then taken up in ethyl acetate (150 ml). The organic phase was washed with saturated sodium chloride solution (3×50 ml), dried over solid sodium sulfate, filtered and concentrated. The residue was subjected to flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 1:1). The title compound was obtained as a colorless solid (550 mg, 77% of theory).
CC1=C(C#N)C(c2ccc(C#N)cc2S(=O)(=O)CCO[Si](C)(C)C(C)(C)C)NC(=O)N1c1cccc(C(F)(F)F)c1
null
CC1=C(C(N)=O)C(c2ccc(C#N)cc2S(=O)(=O)CCO[Si](C)(C)C(C)(C)C)NC(=O)N1c1cccc(C(F)(F)F)c1
null
null
[Si:1]([O:8][CH2:9][CH2:10][S:11]([C:14]1[CH:19]=[C:18]([C:20]#[N:21])[CH:17]=[CH:16][C:15]=1[CH:22]1[C:27]([C:28]([NH2:30])=O)=[C:26]([CH3:31])[N:25]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=2)[C:24](=[O:42])[NH:23]1)(=[O:13])=[O:12])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[OH-].COC(NS([N+](CC)(CC)CC)(=O)=O)=O>C1COCC1.C(OCC)(=O)C>[Si:1]([O:8][CH2:9][CH2:10][S:11]([C:14]1[CH:19]=[C:18]([C:20]#[N:21])[CH:17]=[CH:16][C:15]=1[CH:22]1[C:27]([C:28]#[N:30])=[C:26]([CH3:31])[N:25]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:39])([F:40])[F:41])[CH:33]=2)[C:24](=[O:42])[NH:23]1)(=[O:13])=[O:12])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]
1.25
CCOC(C)=O
C1CCOC1
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
178,122
null
null
null
null
ord_dataset-3ef78abb9a384506b240a419b70e6ceb
1988-01-01T00:09:00
true
Another embodiment of the present invention is the use of pervaporation membranes to separate alcohols from ethers and/or hydrocarbons in a process for producing high purity alkenes by the decomposition of ethers. FIG. 4 depicts such a process for producing high purity isobutene by the decomposition of MTBE, although the present invention can be applied to other ether decomposition reactions. An impure C4 feed stream 70 is combined with a methanol feed stream 71 and recycled methanol stream 72 and fed to an MTBE synthesis system 74. The MTBE synthesis system 74 produces a MTBE product stream 76. A portion of the MTBE product stream 76 is collected as final MTBE product stream 78, while another portion of the MTBE product stream 76 is taken off at stream 80 and is heated and vaporized in the heat exchanger 81 and subsequently fed to a decomposition reactor 82 containing a fixed bed of acid cation exchange resin. The decomposition reactor 82 decomposes the MTBE feed to produce an effluent stream 83 containing isobutene/methanol/MTBE, which is cooled and condensed in heat exchanger 84 to produce a liquid mixture 85 which is subsequently fed through a pervaporation membrane system 86. The isobutene/methanol/MTBE mixture is separated by the pervaporation membrane system 86 to produce a high purity methanol permeate vapor 87 and a methanol-depleted liquid concentrate reject stream 88. The high purity methanol permeate vapor stream 87 is withdrawn from the membrane system, cooled and condensed if necessary, and subsequently recycled to the MTBE synthesis reactor 74 as stream 72. The methanol-depleted liquid concentrate reject stream 88 from the pervaporation membrane system 86 is fed to a distillation column 89 to undergo separation. The high purity isobutene stream 90 is taken as overhead product, and a high purity MTBE stream 91 is taken as bottom product and recycled to the feed to the MTBE decomposer 82. A liquid side draw containing isobutene/MTBE/methanol is taken from the distillation column 89 as stream 93 and is fed through a pervaporation membrane 94 where it is separated to form a high purity methanol vapor permeate stream 95 and isobutene/MTBE stream 96. The high purity methanol vapor permeate stream 95 is subsequently combined with the methanol permeate stream from the first pervaporation membrane system 86 and recycled as combined methanol stream 72 to the MTBE synthesis step 74. The isobutene/MTBE reject stream 96 from pervaporation membrane system 94 is returned to the distillation column 89 for further separation.
C=C(C)C
null
CCOCC
null
null
C[CH2:2][O:3]CC.CO.[CH3:8][C:9]([O:12][CH3:13])([CH3:11])[CH3:10]>>[CH2:8]=[C:9]([CH3:11])[CH3:10].[CH3:2][OH:3].[CH3:8][C:9]([O:12][CH3:13])([CH3:11])[CH3:10]
null
COC(C)(C)C
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,371,299
CN(C)C(On1nnc2cccnc21)=[N+](C)C
F[P-](F)(F)(F)(F)F
null
null
ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81
2013-01-01T00:12:00
true
To a 100 mL round bottom flask was added 4-bromo-3-methoxy-benzoic acid (860 mg, 3.7 mmol), HATU (1.4 g, 3.7 mmol), DMF (6 mL) and triethylamine (1.4 mL, 10 mmol). The reaction mixture was allowed to stir for 10 minutes. 1-Methylspiro[chromeno[4,3-c]pyrazole-4,4′-piperidine] (860 mg, 3.4 mmol) dissolved in DMF (6 mL) was added, and the mixture was allowed to stir at 25° C. After 2 h, the reaction was quenched with brine and was extracted with ethyl acetate. The combined organic layers were washed with brine 3 times. The combined organic layer were dried over sodium sulfate and evaporated. The residue was purified via silica gel chromatography (5-90% EtOAc:hexanes) to give (4-bromo-3-methoxyphenyl)(1-methyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine]-1′-yl)methanone as white foam. ESI-MS m/z calc. 467.1. found 468.2 (M+1)+. Retention time: 3.04 minutes (4 min run).
COc1cc(C(=O)N2CCC3(CC2)Oc2ccccc2-c2c3cnn2C)ccc1Br
null
Cn1ncc2c1-c1ccccc1OC21CCNCC1
COc1cc(C(=O)O)ccc1Br
null
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[O:11][CH3:12].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[CH3:44][N:45]1[C:49]2[C:50]3[CH:51]=[CH:52][CH:53]=[CH:54][C:55]=3[O:56][C:57]3([CH2:62][CH2:61][NH:60][CH2:59][CH2:58]3)[C:48]=2[CH:47]=[N:46]1>CN(C=O)C>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:60]2[CH2:61][CH2:62][C:57]3([C:48]4[CH:47]=[N:46][N:45]([CH3:44])[C:49]=4[C:50]4[CH:51]=[CH:52][CH:53]=[CH:54][C:55]=4[O:56]3)[CH2:58][CH2:59]2)=[O:8])=[CH:4][C:3]=1[O:11][CH3:12]
0.17
CN(C)C=O
CCN(CC)CC
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
136,283
null
null
null
null
ord_dataset-3007013966624a1096d71142f31cb5a3
1985-01-01T00:10:00
true
A mixture of tert-butyl 3(S)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (1.65 g), ethyl 2-bromo-10-phthalimidodecanoate (2.4 g), acetonitrile (100 ml) and triethylamine (0.75 g) is heated at 80° C. for 4 days. After evaporation of the solvent, ethyl acetate (200 ml) and water (100 ml) are added to the residue. The ethyl acetate layer is dried over anhydrous magnesium sulfate and evaporated in vacuo. The oily residue is chromatographed on silica gel using hexane-ethyl acetate (2:1) as an eluent. Evaporation of the first fraction gives tert-butyl 3(S)-[1(R)-ethoxycarbonyl-9-phthalimidononyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (0.45 g) as a colorless oil.
CCOC(=O)[C@@H](CCCCCCCCN1C(=O)c2ccccc2C1=O)N[C@H]1COc2ccccc2N(CC(=O)OC(C)(C)C)C1=O
null
CCOC(=O)C(Br)CCCCCCCCN1C(=O)c2ccccc2C1=O
CC(C)(C)OC(=O)CN1C(=O)[C@@H](N)COc2ccccc21
null
[NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[O:4][CH2:3]1.Br[CH:23]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][N:37]1[C:41](=[O:42])[C:40]2=[CH:43][CH:44]=[CH:45][CH:46]=[C:39]2[C:38]1=[O:47])[C:24]([O:26][CH2:27][CH3:28])=[O:25].C(#N)C>C(N(CC)CC)C>[CH2:27]([O:26][C:24]([C@H:23]([NH:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[O:4][CH2:3]1)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][N:37]1[C:38](=[O:47])[C:39]2=[CH:46][CH:45]=[CH:44][CH:43]=[C:40]2[C:41]1=[O:42])=[O:25])[CH3:28]
null
CCN(CC)CC
CC#N
null
80
12.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,387,422
c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
null
null
null
ord_dataset-31641fb65b34430fa7435229b949b604
2014-01-01T00:01:00
true
N-Methyl-N-(2-{2-[3-(4-methyl-piperazin-1-yl)-phenylamino]-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino}-benzyl)-methanesulfonamide was prepared from N-[2-(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-benzyl]-N-methyl-methanesulfonamide (75.0 mg, 0.205 mmol) and 3-(4-methylpiperazin-1-yl)aniline (44.0 mg, 0.230 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (25.0 mg, 0.0457 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a tan foam (0.033 g, 31%). 1H NMR (400 MHz, CDCl3, δ, ppm): 7.98 (d, J=6.5 Hz, 1H), 7.45-7.39 (m, 2H), 7.35 (t, J=7.6 Hz, 1H), 7.23 (d, J=8.0 Hz, 1H), 7.18-7.11 (m, 3H), 6.96 (s, 1H), 6.81 (d, J=7.9 Hz, 1H), 6.77 (s, 1H), 6.70 (t, J=7.0 Hz, 1H), 6.58 (d, J=8.0 Hz, 1H), 4.36 (s, 2H), 3.28-3.23 (m, 4H), 2.91 (s, 3H), 2.78 (s, 3H), 2.61-2.56 (m, 4H), 2.36 (s, 3H). MS=521 (MH)+.
CN1CCN(c2cccc(Nc3nc4c(Nc5ccccc5CN(C)S(C)(=O)=O)cccn4n3)c2)CC1
null
CN1CCN(c2cccc(N)c2)CC1
CN(Cc1ccccc1Nc1cccn2nc(Cl)nc12)S(C)(=O)=O
null
Cl[C:2]1[N:24]=[C:5]2[C:6]([NH:10][C:11]3[CH:23]=[CH:22][CH:21]=[CH:20][C:12]=3[CH2:13][N:14]([CH3:19])[S:15]([CH3:18])(=[O:17])=[O:16])=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[CH3:25][N:26]1[CH2:31][CH2:30][N:29]([C:32]2[CH:33]=[C:34]([CH:36]=[CH:37][CH:38]=2)[NH2:35])[CH2:28][CH2:27]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:19][N:14]([CH2:13][C:12]1[CH:20]=[CH:21][CH:22]=[CH:23][C:11]=1[NH:10][C:6]1[C:5]2[N:4]([N:3]=[C:2]([NH:35][C:34]3[CH:36]=[CH:37][CH:38]=[C:32]([N:29]4[CH2:28][CH2:27][N:26]([CH3:25])[CH2:31][CH2:30]4)[CH:33]=3)[N:24]=2)[CH:9]=[CH:8][CH:7]=1)[S:15]([CH3:18])(=[O:17])=[O:16]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,138,343
O=C([O-])O
[Na+]
null
null
ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820
2012-01-01T00:02:00
true
To a toluene (30 ml)-methanol (3 ml) solution of the 2-(((3-methyl-4-(1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy)pyridin-2-yl)methyl)thio)-1H-benzimidazole (974 mg, 2.21 mmol) obtained in the step (10d), a toluene (1 ml)-methanol (1 ml) solution of 3-chloroperbenzoic acid (528 mg, 1.99 mmol as the content was regarded as 65%) was added dropwise at −65° C. for 5 minutes in a nitrogen atmosphere. The mixture was stirred for 55 minutes in the same conditions. To the reaction mixture, a saturated aqueous solution of sodium hydrogen carbonate was added. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (NH silica gel: 20 g, elution solvent: dichloromethane, dichloromethane/methanol=10/1). The fractions containing the title compound were collected with ethyl acetate and concentrated. After diethyl ether was added to the residue, the solvent was distilled off to obtain the title compound (725 mg, yield: 71.7%) as a pale grayish solid.
Cc1c(OCC2COC3(CCOCC3)OC2)ccnc1CS(=O)c1nc2ccccc2[nH]1
null
O=C(OO)c1cccc(Cl)c1
Cc1c(OCC2COC3(CCOCC3)OC2)ccnc1CSc1nc2ccccc2[nH]1
null
[CH3:1][C:2]1[C:3]([CH2:21][S:22][C:23]2[NH:27][C:26]3[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=3[N:24]=2)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH:10]1[CH2:15][O:14][C:13]2([CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[O:12][CH2:11]1.ClC1C=CC=C(C(OO)=[O:40])C=1.C(=O)([O-])O.[Na+]>CO.C1(C)C=CC=CC=1>[CH3:1][C:2]1[C:3]([CH2:21][S:22]([C:23]2[NH:24][C:25]3[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=3[N:27]=2)=[O:40])=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH:10]1[CH2:15][O:14][C:13]2([CH2:16][CH2:17][O:18][CH2:19][CH2:20]2)[O:12][CH2:11]1
0.92
Cc1ccccc1
CO
null
null
71.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
708,970
CCOC(=O)/N=N/C(=O)OCC
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
null
ord_dataset-c8069773c1a148aca8ab417108daacc5
2006-01-01T00:05:00
true
3-Acetyl-5-methyl-1-(2-hydroxyethyl)pyrazole (1.74 g), triphenyl-phosphine (4.071 g) and 5-mercapto-1-methyltetrazole (3.605 g) were dissolved in dry THF (125 ml) and cooled to 5° C. under an atmosphere of argon. A solution of diethylazodicarboxylate (2.70 g) in THF (25 ml) was added dropwise to the stirred, cooled solution. Stirring was continued at 5° C. for 4 h. The reaction mixture was then partitioned between ethyl acetate and water. The organic solution was washed with NaHCO3 solution, brine, dried (MgSO4) and evaporated. Silica gel column chromatography provided the title compound (1.25 g), umax (CH2Cl2) 1683 cm−1; dH (CDCl3) 2.30 (3H, s), 2.55 (3H, s), 3.80 (2H, t), 3.92 (3H, s), 4.59 (2H, t), 6.51 (1H, s); m/z 266.0953 (M+), calculated for C10H14N6OS 266.0950.
CC(=O)c1cc(C)n(CCSc2nnnn2C)n1
null
Cn1nnnc1S
CC(=O)c1cc(C)n(CCO)n1
null
[C:1]([C:4]1[CH:8]=[C:7]([CH3:9])[N:6]([CH2:10][CH2:11]O)[N:5]=1)(=[O:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[SH:32][C:33]1[N:37]([CH3:38])[N:36]=[N:35][N:34]=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:1]([C:4]1[CH:8]=[C:7]([CH3:9])[N:6]([CH2:10][CH2:11][S:32][C:33]2[N:37]([CH3:38])[N:36]=[N:35][N:34]=2)[N:5]=1)(=[O:3])[CH3:2]
4
C1CCOC1
null
null
5
45.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,293,631
null
null
null
null
ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c
2013-01-01T00:05:00
true
According to General Method 6A, 300 mg (0.828 mmol) of the compound from Example 7A and 91 mg (0.91 mmol) of N-hydroxycyclopropanecarboximidamide were reacted Yield: 141 mg (40% of theory)
CCc1ccc(C2CC(c3nc(C4CC4)no3)CN(C(=O)N3CCSCC3)C2)cc1
null
N=C(NO)C1CC1
CCc1ccc(C2CC(C(=O)O)CN(C(=O)N3CCSCC3)C2)cc1
null
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][N:13]([C:15]([N:17]3[CH2:22][CH2:21][S:20][CH2:19][CH2:18]3)=[O:16])[CH2:12][CH:11]([C:23](O)=[O:24])[CH2:10]2)=[CH:5][CH:4]=1)[CH3:2].O[NH:27][C:28]([CH:30]1[CH2:32][CH2:31]1)=[NH:29]>>[CH:30]1([C:28]2[N:29]=[C:23]([CH:11]3[CH2:10][CH:9]([C:6]4[CH:7]=[CH:8][C:3]([CH2:1][CH3:2])=[CH:4][CH:5]=4)[CH2:14][N:13]([C:15]([N:17]4[CH2:22][CH2:21][S:20][CH2:19][CH2:18]4)=[O:16])[CH2:12]3)[O:24][N:27]=2)[CH2:32][CH2:31]1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
41,480
null
null
null
null
ord_dataset-48929f64ce614f1181a555eafd7c97a6
1978-01-01T00:06:00
true
Heat 40 g of 3-(5-nitro-2-furyl)-1-phenylpyrazole-4-carboxamide together with 290 ml of thionyl chloride and 1 ml of dimethylformamide for 16 hours at boiling point. Cool the resulting solution, draw off the formed precipitate and wash it with thionyl chloride and with carbon tetrachloride to obtain an 89% yield of 3-(5-nitro-2-furyl)-1-phenylpyrazole-4-carboxylic acid chloride [m.p. 208° to 210° C (from dioxane)].
O=C(Cl)c1cn(-c2ccccc2)nc1-c1ccc([N+](=O)[O-])o1
null
NC(=O)c1cn(-c2ccccc2)nc1-c1ccc([N+](=O)[O-])o1
O=S(Cl)Cl
null
[N+:1]([C:4]1[O:8][C:7]([C:9]2[C:13]([C:14](N)=[O:15])=[CH:12][N:11]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[N:10]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].S(Cl)([Cl:25])=O.CN(C)C=O>C(Cl)(Cl)(Cl)Cl>[N+:1]([C:4]1[O:8][C:7]([C:9]2[C:13]([C:14]([Cl:25])=[O:15])=[CH:12][N:11]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[N:10]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
null
ClC(Cl)(Cl)Cl
CN(C)C=O
null
null
null
89
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,190,581
CC(C)(C)OC(=O)CCNC(=O)CNC(=O)CNC(=O)CN
CCN=C=NCCCN(C)C
Cl
null
ord_dataset-4e81c470cc3b429faf5e1caa50f70a98
2012-01-01T00:08:00
true
513 mg (2.8 mmol) of 4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanoic acid, 800 mg (0.2.8 mmol) tert-butyl 3-(2-(2-(2-aminoacetamido)acetamido)acetamido)propanoate and 583 mg (3.0 mmol) N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride were disolved in 12 mL of dimethyl formamide and stirred for 3 hours. The reaction mixture was purified in four equal portions by reverse phase HPLC using a 5.0 cm×25 cm C18 column. The column was eluted at 100 mL/min with deionized water containing 0.3% formic acid and 5% acetonitrile for 10 min followed by a 13 min linear gradient from 5% acetonitrile to 33% acetonitrile. Product fractions (retention time of 21 min) were combined and solvent was removed by rotary evaporation under vacuum to give 832 mg (62%) of the title compound. 1H NMR (d6-DMSO) 8.10-8.16 (m, 2H), 8.07 (t, J=4.8 Hz, 1H), 7.0-7.15 (m, 1H), 3.747 (t, J=6.0 Hz, 3H), 3.64 (d, J=5.6 Hz, 2H), 3.41 (t, J=6.8, 2H), 3.1-3.33 (m, 1H), 3.19-3.26 (m, 2H), 2.348 (t, J=6.8, 2H), 2.132 (t, J=7.2 Hz, 2H), 1.67-1.76 (m, 2H), 1.39 (s, 9H). 13C NMR (d6-DMSO) 171.80, 170.98, 170.39, 169.48, 168.96, 168.56, 134.37, 79.83, 42.05, 41.83, 37.38, 34.82, 34.71, 32.26, 27.83, 23.95. HRMS (M+Na+) Calc. 504.2070 found 504.2046
NCCCC(=O)O
null
O=C(O)CCCN1C(=O)C=CC1=O
null
null
O=C1C=CC(=O)[N:3]1[CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12].[NH2:14][CH2:15][C:16]([NH:18][CH2:19][C:20]([NH:22][CH2:23][C:24]([NH:26][CH2:27][CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:25])=[O:21])=[O:17].Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[CH2:9]([CH2:8][NH2:3])[CH2:10][C:11]([OH:13])=[O:12].[NH2:14][CH2:15][C:16]([NH:18][CH2:19][C:20]([NH:22][CH2:23][C:24]([NH:26][CH2:27][CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:25])=[O:21])=[O:17]
3
CN(C)C=O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
105,996
null
null
null
null
ord_dataset-e7e9fe3dd42b4f499d5b17fe63bbf336
1983-01-01T00:06:00
true
By substituting 3-[(1,1'-biphenyl)-2-yloxy]-2-hydroxypropylamine (4.88 g, 0.0174 moles) for the starting material of Example 2 and following the method of Example 2, the desired compound is obtained.
OC(CNc1ncnc2[nH]cnc12)COc1ccccc1-c1ccccc1
null
OC(CNc1ncnc2[nH]cnc12)COc1cccc2ccccc12
NCC(O)COc1ccccc1-c1ccccc1
null
[C:1]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[O:7][CH2:8][CH:9]([OH:12])[CH2:10][NH2:11].OC(COC1C2C(=CC=CC=2)C=CC=1)CN[C:23]1[N:31]=[CH:30][N:29]=[C:28]2[C:24]=1[N:25]=[CH:26][NH:27]2>>[C:1]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[O:7][CH2:8][CH:9]([OH:12])[CH2:10][NH:11][C:23]1[N:31]=[CH:30][N:29]=[C:28]2[C:24]=1[N:25]=[CH:26][NH:27]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
1,736,331
null
null
null
null
ord_dataset-eacfee6d16d8455a93348409f1b37be4
2016-01-01T00:06:00
true
N-(5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-methylnicotinamide (260 mg, 0.745 mmol) and (R)-tert-butyl piperidin-3-ylcarbamate (447 mg, 2.23 mmol) in n-BuOH (3 mL) was heated to 155° C. in a sealed tube. The reaction was then cooled to room temperature and concentrated to dryness. The crude residue was purified by reverse phase HPLC to give (R)-tert-butyl 1-(5-bromo-3-(6-methylnicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (12 mg, 3% yield).
Cc1ccc(C(=O)Nc2c[nH]c3ncc(Br)c(N4CCC[C@@H](NC(=O)OC(C)(C)C)C4)c23)cn1
null
CC(C)(C)OC(=O)N[C@@H]1CCCNC1
Cc1ccc(C(=O)Nc2c[nH]c3ncc(Br)c(F)c23)cn1
null
[Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12](=[O:20])[C:13]3[CH:18]=[CH:17][C:16]([CH3:19])=[N:15][CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[NH:22]1[CH2:27][CH2:26][CH2:25][C@@H:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:23]1>CCCCO>[Br:1][C:2]1[C:3]([N:22]2[CH2:27][CH2:26][CH2:25][C@@H:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])[CH2:23]2)=[C:4]2[C:10]([NH:11][C:12](=[O:20])[C:13]3[CH:18]=[CH:17][C:16]([CH3:19])=[N:15][CH:14]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
null
CCCCO
null
null
25
null
3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,431,981
Cl
[Na+]
null
null
ord_dataset-5e6956e6e8c24a168866a253f4a66c6c
2014-01-01T00:05:00
true
tert-Butyl 2-methylspiro[inden-1,4′-piperidine]-1′-carboxylate (1.19 g, 3.98 mmol) obtained in step 2 was dissolved in 4 mol/L hydrogen chloride-1,4-dioxane (6 mL), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added to the obtained residue, and the mixture was suction-filtered to give white crystals. Saturated aqueous sodium hydrogen carbonate solution was added to the white crystals, and the mixture was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, and concentrated under reduced pressure to give the title compound (0.790 g, 72%).
CC1=Cc2ccccc2C12CCNCC2
null
O=C([O-])O
C1COCCO1
O=C(O)c1cnn2c(NCc3cccc(F)c3)c(C(=O)N3CCC(c4ccccc4)CC3)cnc12
FC1C=C(C=CC=1)CNC1N2N=CC(C(O)=O)=C2N=CC=1C([N:21]1[CH2:26][CH2:25][CH:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:23][CH2:22]1)=O.[C:36](=O)([O-])O.[Na+].O1[CH2:46][CH2:45]OCC1.Cl>>[CH3:36][C:45]1[C:24]2([CH2:23][CH2:22][NH:21][CH2:26][CH2:25]2)[C:27]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:46]=1
2
null
null
null
25
null
72
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
711,802
O=C([O-])O
[Na+]
null
null
ord_dataset-c8a367b56b4f406b878f51867b157d19
2006-01-01T00:06:00
true
1-Cyclobutyl-5-hydroxymethyl-3-methyl-1,3-dihydro-benzoimidazol-2-one (13.79 g, 59.4 mmol) was diluted with dichloromethane (300 mL) and triethylamine (12.4 mL). The reaction was cooled to 0° C. and methanesulfonyl chloride (6.9 mL, 89.1 mmol) was added. The mixture was stirred for 1 hour at 0° C. then was diluted with saturated sodium bicarbonate and extraced into dichloromethane. The organic layer was dried over sodium sulfate and concentrated. The resulting oil was filtered through silica gel using ethyl acetate containing 1% triethylamine as eluent to give 11.92 g of 5-Chloromethyl-1-cyclobutyl-3-methyl-1,3-dihydro-benzoimidazol-2-one.
Cn1c(=O)n(C2CCC2)c2ccc(CCl)cc21
null
Cn1c(=O)n(C2CCC2)c2ccc(CO)cc21
CS(=O)(=O)Cl
null
[CH:1]1([N:5]2[C:9]3[CH:10]=[CH:11][C:12]([CH2:14]O)=[CH:13][C:8]=3[N:7]([CH3:16])[C:6]2=[O:17])[CH2:4][CH2:3][CH2:2]1.CS([Cl:22])(=O)=O>ClCCl.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>[Cl:22][CH2:14][C:12]1[CH:11]=[CH:10][C:9]2[N:5]([CH:1]3[CH2:4][CH2:3][CH2:2]3)[C:6](=[O:17])[N:7]([CH3:16])[C:8]=2[CH:13]=1
1
CCN(CC)CC
ClCCl
null
0
null
80
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
147,456
null
null
null
null
ord_dataset-2069a3db775a4d9f9310aca092ecbad8
1986-01-01T00:08:00
true
A solution of N-allyl-N-chloromethyldichloroacetamide (21.7 g., 0.1 mole) and 2-methoxyethanol (8.4 g., 8.7 ml., 0.11 mole) in dry chloroform (50 ml.) is placed in a round-bottomed, four-necked flask of 250 ml., equipped with a calcium chloride tube, reflux condenser, mechanical stirrer, dropping funnel and thermometer. Triethylamine (10.1 g., 13.9 ml., 0.1 mole) is added under stirring and external cooling in such a rate that the temperature does not exceed 35° C. After the addition is complete, the mixture is stirred for an additional 2 hours at room temperature. The mixture is washed with water (2×70 ml) for removing the triethylamine hydrochloride formed, the chloroform solution is dried over anhydrous sodium sulfate and, after distillation of the chloroform, the product is dried under reduced pressure to give 23.6 g. (92%) of a pale yellow oil which is the named compound of 95% purity according to an analysis by gas chromatography; nD25 =1.4801. This product is directly useful for practical purposes.
C=CCN(COCCOC)C(=O)C(Cl)Cl
null
C=CCN(CCl)C(=O)C(Cl)Cl
COCCO
null
[CH2:1]([N:4]([CH2:10]Cl)[C:5](=[O:9])[CH:6]([Cl:8])[Cl:7])[CH:2]=[CH2:3].[CH3:12][O:13][CH2:14][CH2:15][OH:16].C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH2:1]([N:4]([CH2:10][O:16][CH2:15][CH2:14][O:13][CH3:12])[C:5](=[O:9])[CH:6]([Cl:8])[Cl:7])[CH:2]=[CH2:3]
null
CCN(CC)CC
ClC(Cl)Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,458,472
null
null
null
null
ord_dataset-a86112d52cd54525a5e36d41f18aced2
2014-01-01T00:07:00
true
Methyl 3-amino-2[(tert-butoxycarbonyl)amino]benzoate (61.8 g, 232 mmol) was added to trifluoroacetic acid (250 mL), and the mixture was stirred at room temperature for 3 hr. Trifluoroacetic acid was evaporated in vacuo, and the resulting solid was suspended in ethyl acetate (200 mL), collected by filtration and washed with ethyl acetate (50 mL). The solid was partitioned between ethyl acetate (300 mL) and saturated aqueous sodium hydrogen carbonate (400 mL), and the aqueous layer was seated and extracted with ethyl acetate (300 mL). The combined organic layer was washed with water (300 mL×2) and concentrated in vacuo to give the title compound (24.6 g, 148 mmol, 64%) as a brown solid. The filtrate described above was concentrated in vacuo, and the resulting solid was collected by filtration and washed with ethyl acetate. The filtrate was concentrated in vacuo, and the resulting solid was collected by filtration and washed with diethyl ether. The combined solid was partitioned between ethyl acetate (100 mL) and saturated aqueous sodium hydrogen carbonate (100 mL), and the aqueous layer was seated and extracted with ethyl acetate). The combined organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give the title compound (8.29 g, 49.9 mmol, 22%) as a brown solid. Total amount: 32.9 g, 198 mmol, 85%.
COC(=O)c1cccc(N)c1N
null
COC(=O)c1cccc(N)c1NC(=O)OC(C)(C)C
null
null
[NH2:1][C:2]1[C:3]([NH:12]C(OC(C)(C)C)=O)=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]>FC(F)(F)C(O)=O>[NH2:12][C:3]1[C:2]([NH2:1])=[CH:11][CH:10]=[CH:9][C:4]=1[C:5]([O:7][CH3:8])=[O:6]
3
O=C(O)C(F)(F)F
null
null
25
null
63.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,101,268
O=C(O)CN1CCC(c2ccc(F)cc2)(c2ccc(F)cc2)C1=O
[H]/N=C(\NO)c1ccc(C(F)(F)F)cc1
null
null
ord_dataset-af85e6f81c2d49f08086afd6d9e6959c
2011-01-01T00:10:00
true
The title compound was prepared using the procedure described in Example 190 substituting 2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetic acid from Example 1C for 2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid and (Z)-4-fluoro-N-hydroxybenzimidamide for (Z)—N-hydroxy-4-(trifluoromethyl)benzimidamide. 1H NMR (300 MHz, CDCl3) δ ppm 8.02-7.96 (m, 2H), 7.45-7.27 (m, 10H), 7.18-7.11 (m, 2H), 4.88 (s, 2H), 3.57 (t, J=6.5, 2H), 2.88 (t, J=6.5, 2H); MS (DCI) m/z 414.1 (M+H)+.
O=C1N(Cc2nc(-c3ccc(F)cc3)no2)CCC1(c1ccccc1)c1ccccc1
null
O=C(O)CN1CCC(c2ccccc2)(c2ccccc2)C1=O
[H]/N=C(\NO)c1ccc(F)cc1
null
[O:1]=[C:2]1[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:5][CH2:4][N:3]1[CH2:19][C:20](O)=[O:21].FC1C=CC(C2(C3C=CC(F)=CC=3)CCN(CC(O)=O)C2=O)=CC=1.[F:47][C:48]1[CH:58]=[CH:57][C:51](/[C:52](=[N:55]/[H])/[NH:53]O)=[CH:50][CH:49]=1.ON/C(=N\[H])/C1C=CC(C(F)(F)F)=CC=1>>[F:47][C:48]1[CH:58]=[CH:57][C:51]([C:52]2[N:55]=[C:20]([CH2:19][N:3]3[CH2:4][CH2:5][C:6]([C:7]4[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=4)([C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:2]3=[O:1])[O:21][N:53]=2)=[CH:50][CH:49]=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
1,623,898
C(=NC1CCCCC1)=NC1CCCCC1
CN(C)c1ccncc1
null
null
ord_dataset-35c51552812941cda45194a013d34bb9
2015-01-01T00:08:00
true
A mixture of 2-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)ethanamine (0.1 g, 0.411 mmol), 3-methylpyridine-4-carboxylic acid (0.056 g, 0.411 mmol), N,N′-dicyclohexylcarbodiimide (0.093 g, 0.452 mmol) and 4-dimethylaminopyridine (0.055 g, 0.452 mmol) in dry dichloromethane (2.0 ml) were stirred at room temperature for 4 h. To the reaction mixture was added 10 ml of water and the product extracted with dichloromethane (10 ml×3). Combined dichloromethane layers were dried over sodium sulfate and concentrated under reduced pressure to obtain 7 mg of N-(2-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)ethyl)-3-methylpyridine-4-carboxamide as TFA salt after purification by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min, injection vol. 5 ml). 1H NMR (DMSO) 10.05 (bs, 1H), 8.7 (t, 1H), 8.45-8.55 (m, 2H), 7.4 (d, 1H), 7.22 (s, 1H), 7.15 (d, 1H), 7.0 (d, 1H), 4.6 (d, 1H), 3.72-3.85 (m, 3H), 3.4-3.6 (m, 3H), 3.1-3.2 (m, 3H), 3.0 (s, 3H), 2.4 (s, 3H), 2.2 (s, 3H).
Cc1ccc2c(c1)c1c(n2CCNC(=O)c2ccncc2C)CCN(C)C1
null
Cc1ccc2c(c1)c1c(n2CCN)CCN(C)C1
Cc1cnccc1C(=O)O
null
[CH3:1][N:2]1[CH2:18][CH2:17][C:5]2[N:6]([CH2:14][CH2:15][NH2:16])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[CH3:19][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][C:25]=1[C:26](O)=[O:27].C1(N=C=NC2CCCCC2)CCCCC1.O>CN(C)C1C=CN=CC=1.ClCCl>[CH3:1][N:2]1[CH2:18][CH2:17][C:5]2[N:6]([CH2:14][CH2:15][NH:16][C:26]([C:25]3[CH:24]=[CH:23][N:22]=[CH:21][C:20]=3[CH3:19])=[O:27])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1
4
ClCCl
O
null
25
4.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,564,006
O=S(=O)(O)O
null
null
null
ord_dataset-4e54080057a44c3887653391e24c90b6
2015-01-01T00:03:00
true
To an ice-cold solution of concentrated sulphuric acid (2 ml) is added a second solution of 2-(5-bromo-2-ethylphenyl)-4,4,6,6-tetramethyl-1,5-dioxaspiro[2.4]heptan-7-one (0.995 g, 2.82 mmol) in 1,2-dichloroethane (2 ml) dropwise over 5 minutes. This biphasic mixture is stirred vigorously for 1 hour at 0° C., then poured into ice-cold water (15 ml). This aqueous mixture is then concentrated under vacuum to remove all organic volatiles, producing a free-flowing solid. The solid is filtered, dried under vacuum, then washed with hexanes to afford 4-(5-bromo-2-ethylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione (0.81 g) as a cream-coloured solid.
CCc1ccc(Br)cc1C1C(=O)C(C)(C)OC(C)(C)C1=O
null
CCc1ccc(Br)cc1C1OC12C(=O)C(C)(C)OC2(C)C
null
null
S(=O)(=O)(O)O.[Br:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:25][CH3:26])=[C:11]([CH:13]2[C:15]3([C:19](=[O:20])[C:18]([CH3:22])([CH3:21])[O:17][C:16]3([CH3:24])[CH3:23])[O:14]2)[CH:12]=1>ClCCCl>[Br:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:25][CH3:26])=[C:11]([CH:13]2[C:19](=[O:20])[C:18]([CH3:21])([CH3:22])[O:17][C:16]([CH3:24])([CH3:23])[C:15]2=[O:14])[CH:12]=1
1
ClCCCl
null
null
0
81.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,519,377
[H-]
[Na+]
null
null
ord_dataset-8c74302143c04eb9983e4b3a7ead2d72
2014-01-01T00:12:00
true
Sodium hydride (60% in mineral oil, 0.32 g, 8.00 mmol) was suspended in dry DMF (15 mL) under argon. To this was added Intermediate 10a (1.05 g, 4.00 mmol) followed by 2-chloro-4-nitropyridine (0.64 g, 4.02 mmol). The dark coloured mixture was stirred at RT under argon for 30 min. The reaction mixture was diluted with water and extracted with DCM (3×30 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered, concentrated in vacuo. Purification by FCC, eluting with 0-70% ethyl acetate in cyclohexane, gave the title compound as a white foam (1.43 g, 95%). LCMS (Method 3): Rt 4.22 min, m/z 373.1 [MH+].
CC(C)(C)OC(=O)N[C@H]1CC[C@H](Oc2ccnc(Cl)c2)c2ccccc21
null
CC(C)(C)OC(=O)N[C@H]1CC[C@H](O)c2ccccc21
O=[N+]([O-])c1ccnc(Cl)c1
null
[H-].[Na+].[C:3]([O:7][C:8](=[O:21])[NH:9][C@@H:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C@@H:13]([OH:20])[CH2:12][CH2:11]1)([CH3:6])([CH3:5])[CH3:4].[Cl:22][C:23]1[CH:28]=[C:27]([N+]([O-])=O)[CH:26]=[CH:25][N:24]=1>CN(C=O)C.O>[C:3]([O:7][C:8](=[O:21])[NH:9][C@@H:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C@@H:13]([O:20][C:27]2[CH:26]=[CH:25][N:24]=[C:23]([Cl:22])[CH:28]=2)[CH2:12][CH2:11]1)([CH3:6])([CH3:4])[CH3:5]
0.5
O
CN(C)C=O
null
25
95.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,235,709
null
null
null
null
ord_dataset-e96f5a2842f14e5380461c234100f05a
2012-01-01T00:12:00
true
To a solution of 72 (2.9 g, 11.9 mmol) in toluene (20 ml) at RT was added SOCl2 (2.83 g, 2 eq, 23.8 mmol) and the mixture was heated to 60° C. for 3 hrs. The solvent was removed and the crude was dissolved in EtOAc then partitioned between water and satd NaHCO3 soln. The organic phase was collected, dried over Na2SO4, filtered and concentrated. The crude was purified by column chromatography (20% EtOAc in hexane) to afford 73 as a brown oil (2.9 g, 93% yield). 1H NMR (DMSO-d6) δ (ppm): 7.45 (m, 2H), 7.21 (m, 2H), 3.57 (t, J=6.85 Hz, 2H), 3.52 (s, 2H), 2.74 (t, J=6.85 Hz, 2H), 2.26 (s, 3H).
CN(CCCl)Cc1ccc(Br)cc1
null
O=S(Cl)Cl
CN(CCO)Cc1ccc(Br)cc1
null
[Br:1][C:2]1[CH:13]=[CH:12][C:5]([CH2:6][N:7]([CH3:11])[CH2:8][CH2:9]O)=[CH:4][CH:3]=1.O=S(Cl)[Cl:16]>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:13]=[CH:12][C:5]([CH2:6][N:7]([CH3:11])[CH2:8][CH2:9][Cl:16])=[CH:4][CH:3]=1
null
Cc1ccccc1
null
null
60
null
92.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,627,440
null
null
null
null
ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d
2015-01-01T00:09:00
true
Trifluoromethanesulfonic anhydride (1.76 mL) was added at 0 C to a mixture of tert-butyl 4-(3-ethyl-4-hydroxy-2-oxopyridin-1(2H)-yl)piperidine-1-carboxylate (1.12 g) in pyridine (17.4 mL), and the mixture was stirred at 0 C for 30 minutes in a nitrogen atmosphere. Water was added thereto, and then, the solvent was distilled off under reduced pressure. Water was added again to the residue, followed by extraction with ethyl acetate. The obtained organic layer was washed with 1 M hydrochloric acid and saturated saline in this order and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (1.14 g).
CCc1c(OS(=O)(=O)C(F)(F)F)ccn(C2CCN(C(=O)OC(C)(C)C)CC2)c1=O
null
O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
CCc1c(O)ccn(C2CCN(C(=O)OC(C)(C)C)CC2)c1=O
null
[F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].[CH2:16]([C:18]1[C:19](=[O:38])[N:20]([CH:25]2[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]2)[CH:21]=[CH:22][C:23]=1O)[CH3:17].O>N1C=CC=CC=1>[CH2:16]([C:18]1[C:19](=[O:38])[N:20]([CH:25]2[CH2:26][CH2:27][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:29][CH2:30]2)[CH:21]=[CH:22][C:23]=1[O:6][S:3]([C:2]([F:15])([F:14])[F:1])(=[O:5])=[O:4])[CH3:17]
0.5
c1ccncc1
O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
228,729
null
null
null
null
ord_dataset-9adbd9cd2fd941f7af27fb31c9bf3bac
1991-01-01T00:06:00
true
Nicotinealdehyde (2.16 ml, 22.9 mmol) and N,N-dimethylethylenediamine (2.51 ml, 22.9 mmol) were added to toluene (100 ml) and the mixture was subjected to azeotropic dehydration for 2 hours. After cooling, solvent was distilled off to obtain N-nicotinylidene-N',N'-dimethylethylenediamine (4.13 g, yield 102%).
CN(C)CCN=Cc1cccnc1
null
CN(C)CCN
O=Cc1cccnc1
null
[CH:1]1[CH:6]=[N:5][CH:4]=[C:3]([CH:7]=O)[CH:2]=1.[CH3:9][N:10]([CH3:14])[CH2:11][CH2:12][NH2:13]>C1(C)C=CC=CC=1>[CH:7](=[N:13][CH2:12][CH2:11][N:10]([CH3:14])[CH3:9])[C:3]1[CH:2]=[CH:1][CH:6]=[N:5][CH:4]=1
2
Cc1ccccc1
null
null
null
null
101.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
363,312
CCN=C=NCCCN(C)C
Cl
Oc1cccc2[nH]nnc12
null
ord_dataset-0b24d1f58a024ed7bc2bda95b2430c72
1997-01-01T00:04:00
true
To a solution of 2.8 g of (3aRS,7RS,7aSR)-7-hydroxy-7-(2-methoxyphenyl)-4-perhydroisoindolone and 1.3 cm3 of triethylamine in 60 cm3 of anhydrous dichloromethane are added 1.55 g of (2-methoxyphenyl)acetic acid, 0.03 g of hydroxybenzotriazole hydrate and 1.96 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. After stirring for 20 hours at 20° C., the reaction mixture is washed with 100 cm3 of water, dried over magnesium sulphate and then concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is recrystallized in ethyl ether and the crystals are drained and then dried under reduced pressure (2.7 kPa). 3.1 g of (3aRS,7RS,7aSR)-7-hydroxy-7-(2-methoxyphenyl)-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolone are obtained, in the form of a white solid melting at 184° C.
COc1ccccc1CC(=O)N1CC2C(=O)CCC(O)(c3ccccc3OC)C2C1
null
COc1ccccc1CC(=O)O
COc1ccccc1C1(O)CCC(=O)C2CNCC21
null
[OH:1][C:2]1([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[O:18][CH3:19])[CH:10]2[CH:6]([CH2:7][NH:8][CH2:9]2)[C:5](=[O:11])[CH2:4][CH2:3]1.C(N(CC)CC)C.[CH3:27][O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH2:35][C:36](O)=[O:37].Cl.CN(C)CCCN=C=NCC>ClCCl.O.OC1C2N=NNC=2C=CC=1>[OH:1][C:2]1([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[O:18][CH3:19])[CH:10]2[CH:6]([CH2:7][N:8]([C:36](=[O:37])[CH2:35][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=3[O:28][CH3:27])[CH2:9]2)[C:5](=[O:11])[CH2:4][CH2:3]1
20
O
ClCCl
CCN(CC)CC
20
null
81.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
643,138
CNCc1cc2ccccc2n1C
COC(=O)C[C@H]1Nc2ccc(C(=O)O)cc2CN(C)C1=O
null
null
ord_dataset-ce71a906ea9c4399a2014cbaaff88c8f
2004-01-01T00:07:00
true
According to the procedure of Example 1 (a), except substituting 5-benzyloxy-1-methyl-2-(methylaminomethyl)indole (0.42 g, 1.50 mmole) for the 1-methyl-2-(methylaminomethyl)indole, and substituting (2R)-2-(hydroxymethyl)-4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxylic acid (0.34 g, 1.37 mmole) for the (2R)-2-[(carbomethoxy)methyl]-4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxylic acid, the title compound (0.66 g, 94%) was prepared as an off-white solid: MS (ES) m/e 513 (M+H)+.
CN(Cc1cc2cc(OCc3ccccc3)ccc2n1C)C(=O)c1ccc2c(c1)CN(C)C(=O)[C@@H](CO)N2
null
CNCc1cc2cc(OCc3ccccc3)ccc2n1C
CN1Cc2cc(C(=O)O)ccc2N[C@H](CO)C1=O
null
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH3:18])[C:13]([CH2:19][NH:20][CH3:21])=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1C2C(=CC=CC=2)C=C1CNC.[OH:35][CH2:36][C@@H:37]1[C:43](=[O:44])[N:42]([CH3:45])[CH2:41][C:40]2[CH:46]=[C:47]([C:50](O)=[O:51])[CH:48]=[CH:49][C:39]=2[NH:38]1.C(C[C@@H]1C(=O)N(C)CC2C=C(C(O)=O)C=CC=2N1)(OC)=O>>[CH3:21][N:20]([CH2:19][C:13]1[N:14]([CH3:18])[C:15]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[CH:17][CH:16]=2)[C:50]([C:47]1[CH:48]=[CH:49][C:39]2[NH:38][C@H:37]([CH2:36][OH:35])[C:43](=[O:44])[N:42]([CH3:45])[CH2:41][C:40]=2[CH:46]=1)=[O:51]
null
null
null
null
null
null
94
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,226,230
null
null
null
null
ord_dataset-cde802cdb7434a5f82a22981ccaefc4e
2012-01-01T00:11:00
true
To a stirred solution of bis(trichloromethyl) carbonate (0.26 mmol, 76 mg) in dichloromethane (3 mL) was added a mixture of 3-((4-(4-amino-2,3-difluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylbenzamide (0.6 mmol, 257 mg) and N-ethyl-N-isopropylpropan-2-amine (0.11 mL) in dichloromethane (2 mL) dropwise over 2 minutes. After 30 minutes stirring, a mixture of cyclobutylamine (1.192 mmol, 0.113 mL, 85 mg) and N-ethyl-N-isopropylpropan-2-amine (0.22 mL) was added. After 2 hours stirring, the reaction mixture was diluted with dichloromethane and water. The organic layer separated, dried with sodium sulfate and purified by basic reverse phase HPLC. The water/acetonitrile fractions were concentrated under vacuum. The residue was taken up in dichloromethane (1 mL) and 2M hydrochloric acid (2 mL) in ether was added. The volatiles were removed under reduced pressure. Drying in a vacuum oven over night at 50° C. gave the title compound (170 mg). MS (ESI) m/z 528.5[M+H]+
CC(C)(C)NC(=O)c1cccc(CN2CCN(C(=O)c3ccc(NC(=O)NC4CCC4)c(F)c3F)CC2)c1
Cl
CC(C)(C)NC(=O)c1cccc(CN2CCN(C(=O)c3ccc(N)c(F)c3F)CC2)c1
NC1CCC1
O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
[C:1](=[O:12])(OC(Cl)(Cl)Cl)OC(Cl)(Cl)[Cl:4].[NH2:13][C:14]1[CH:41]=[CH:40][C:17]([C:18]([N:20]2[CH2:25][CH2:24][N:23]([CH2:26][C:27]3[CH:28]=[C:29]([CH:37]=[CH:38][CH:39]=3)[C:30]([NH:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:22][CH2:21]2)=[O:19])=[C:16]([F:42])[C:15]=1[F:43].C(N(C(C)C)C(C)C)C.[CH:53]1([NH2:57])[CH2:56][CH2:55][CH2:54]1>ClCCl.O>[ClH:4].[C:33]([NH:32][C:30](=[O:31])[C:29]1[CH:37]=[CH:38][CH:39]=[C:27]([CH2:26][N:23]2[CH2:22][CH2:21][N:20]([C:18](=[O:19])[C:17]3[CH:40]=[CH:41][C:14]([NH:13][C:1]([NH:57][CH:53]4[CH2:56][CH2:55][CH2:54]4)=[O:12])=[C:15]([F:43])[C:16]=3[F:42])[CH2:25][CH2:24]2)[CH:28]=1)([CH3:36])([CH3:35])[CH3:34]
0.5
ClCCl
O
CCN(C(C)C)C(C)C
null
115.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
855,309
Cl
c1cc[nH+]cc1
null
null
ord_dataset-faa0236be76c4501841c954527cd1b6c
2008-01-01T00:12:00
true
To a solution of (R,S)-1-[2-(1-Hydroxy-propyl)-phenyl]-propan-1-ol (1.0 g, 5.15 mmol) in pyridine (1.22 g, 15.4 mmol) was added under exclusion of moisture phenyl phosphonic acid dichloride (1.0 g, 5.15 mmol). There is an exotherm and instant formation of pyridinium hydrochloride. The mixture was stirred over night. By 31P-NMR of the crude mixture there was complete conversion, and only one of two possible diastereoisomers present. After addition of HCl (5 ml of 4 N solution) the product was extracted with TBME (20 ml).
CC[C@@H]1OP(=O)(c2ccccc2)O[C@H](CC)c2ccccc21
null
CC[C@@H](O)c1ccccc1[C@@H](O)CC
O=P(Cl)(Cl)c1ccccc1
null
[OH:1][C@H:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C@H:11]([OH:14])[CH2:12][CH3:13])[CH2:3][CH3:4].N1C=CC=CC=1.[C:21]1([P:27](Cl)(Cl)=[O:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl.[NH+]1C=CC=CC=1.Cl>>[CH2:3]([C@@H:2]1[C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C@H:11]([CH2:12][CH3:13])[O:14][P:27](=[O:28])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:1]1)[CH3:4]
null
c1ccncc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
202,536
null
null
null
null
ord_dataset-19e5fc80c1554f4f8641c835e055f02b
1990-01-01T00:01:00
true
Cyclopropylmethyl bromide (1.0 ml) was added to a solution of (2β,3α,5α,16β,17β)-2-(4-morpholinyl)-16-(1-pyrrolidinyl)-androstane-3,17-diol diacetate (2.0 g) in acetonitrile (20 ml) and the solution was heated under reflux for 14 d. Evaporation of the reaction mixture to dryness under reduced pressure gave a pale brown solid (2.30 g), which was crystallised from dichloro-methanediethyl ether to remove most of the unreacted starting material. Further purification, by chromatography on alumina as described above, gave material, which was dissolved in dichloro-methane and precipitated from the solution with diethyl ether to give 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(4-morpholinyl)-androstan-16-yl]-1-(cyclopropylmethyl) pyrrolidinium bromide, m.p. decomposes above 175° C.; [α]D20 =-11.6° (c 0.66 in CHCl3).
CC(=O)O[C@H]1C[C@H]2CC[C@@H]3[C@H](CC[C@@]4(C)[C@H]3C[C@@H]([N+]3(CC5CC5)CCCC3)[C@@H]4OC(C)=O)[C@@]2(C)C[C@@H]1N1CCOCC1
[Br-]
BrCC1CC1
CC(=O)O[C@H]1C[C@@H]2CC[C@@H]3[C@H](CC[C@@]4(C)[C@H]3C[C@H](N3CCCC3)[C@@H]4OC(C)=O)[C@@]2(C)C[C@@H]1N1CCOCC1
null
[CH:1]1([CH2:4][Br:5])[CH2:3][CH2:2]1.[C:6]([O:9][C@@H:10]1[C@@H:27]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[CH2:26][C@@:25]2([CH3:34])[C@@H:12]([CH2:13][CH2:14][C@@H:15]3[C@@H:24]2[CH2:23][CH2:22][C@@:20]2([CH3:21])[C@H:16]3[CH2:17][C@H:18]([N:39]3[CH2:43][CH2:42][CH2:41][CH2:40]3)[C@@H:19]2[O:35][C:36](=[O:38])[CH3:37])[CH2:11]1)(=[O:8])[CH3:7]>C(#N)C>[Br-:5].[C:6]([O:9][C@@H:10]1[C@@H:27]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[CH2:26][C@@:25]2([CH3:34])[C@H:12]([CH2:13][CH2:14][C@@H:15]3[C@@H:24]2[CH2:23][CH2:22][C@@:20]2([CH3:21])[C@H:16]3[CH2:17][C@@H:18]([N+:39]3([CH2:4][CH:1]4[CH2:3][CH2:2]4)[CH2:40][CH2:41][CH2:42][CH2:43]3)[C@@H:19]2[O:35][C:36](=[O:38])[CH3:37])[CH2:11]1)(=[O:8])[CH3:7]
null
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
107,550
C1CCCC(C2CCCCCCC2)CCC1
O=C(Cl)Cl
null
null
ord_dataset-29d79fca4cec4a43b773d0ba25b27651
1983-01-01T00:08:00
true
A mixture of 18.8 g of N-butylaminocarbonyl-4-methyl-3-thiophenesulfonamide, 0.3 g of 1,4-diaza[2.2.2.]bicyclooctane and 100 ml of dry xylenes was heated to reflux (136° C.) and 7.4 g of phosgene was then added at a rate to maintain the temperature at above 125°. The mixture was refluxed for three and one half hours after the addition was completed. It was then cooled, filtered and concentrated in vacuo to yield a dark oil, (15 g) which showed absorption in the infrared spectrum at 2250 cm-1. This intermediate was used without further purification.
Cc1cscc1S(=O)(=O)N=C=O
null
CCCCNC(=O)NS(=O)(=O)c1cscc1C
null
null
C(N[C:6]([NH:8][S:9]([C:12]1[C:16]([CH3:17])=[CH:15][S:14][CH:13]=1)(=[O:11])=[O:10])=[O:7])CCC.C1(C2CCCCCCC2)CCCCCCC1.C(Cl)(Cl)=O>>[CH3:17][C:16]1[C:12]([S:9]([N:8]=[C:6]=[O:7])(=[O:10])=[O:11])=[CH:13][S:14][CH:15]=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
1,417,786
[NH4+]
[OH-]
null
null
ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f
2014-01-01T00:04:00
true
A solution of Example 42C (2.0 g, 3.9 mmol) and copper(I) cyanide (1.047 g, 11.69 mmol) in DMF (19 mL) was heated in a microwave for 7 hours at 160° C. Afterwards the mixture was poured in water (700 mL) and then concentrated ammonium hydroxide (40 mL) was added and the solution extracted with EtOAc. The organic extract was dried, filtered, concentrated and the residue purified by flash chromatography (silica gel, EtOAc/hexanes) to afford 1.23 g (78%) of the title compound. MS (ESI) m/z 406 (M+H)+.
CC(C)(C)c1ccc(N2C(c3ccc(C#N)cc3)CCC2c2ccc(C#N)cc2)cc1
null
CC(C)(C)c1ccc(N2C(c3ccc(Br)cc3)CCC2c2ccc(Br)cc2)cc1
N#C[Cu]
CN(C)C=O
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH:10]([C:13]3[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=3)[N:9]2[C:20]2[CH:25]=[CH:24][C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:22][CH:21]=2)=[CH:4][CH:3]=1.[Cu][C:31]#[N:32].[OH-].[NH4+].[CH3:35][N:36](C=O)C>O>[C:26]([C:23]1[CH:24]=[CH:25][C:20]([N:9]2[CH:8]([C:5]3[CH:6]=[CH:7][C:2]([C:35]#[N:36])=[CH:3][CH:4]=3)[CH2:12][CH2:11][CH:10]2[C:13]2[CH:18]=[CH:17][C:16]([C:31]#[N:32])=[CH:15][CH:14]=2)=[CH:21][CH:22]=1)([CH3:28])([CH3:29])[CH3:27]
null
O
null
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
56,613
[OH-]
null
null
null
ord_dataset-12a0ec4f3cda46e2badc694da2072c39
1979-01-01T00:06:00
true
A mixture of 35 g of 2-bromo-2-(4-chlorophenyl)-1-(2-thienyl)ethanone and 200 ml of formamide was refluxed under an air condenser for two hours. It was cooled, poured into water and the pH adjusted to 8-9 by adding ammonium hydroxide. Chloroform was added to the solution, and solid separated and was filtered and washed with chloroform; yield 19.3 g. This was recrystallized from dimethylformamide, filtered and washed with acetonitrile; yield 14.7 g, m.p. 244°-245° C.
Clc1ccc(-c2nc[nH]c2-c2cccs2)cc1
null
O=C(c1cccs1)C(Br)c1ccc(Cl)cc1
[NH4+]
NC=O
Br[CH:2]([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)[C:3]([C:5]1[S:6][CH:7]=[CH:8][CH:9]=1)=O.[CH:17]([NH2:19])=O.O.[OH-].[NH4+:22]>C(Cl)(Cl)Cl>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([C:2]2[N:22]=[CH:17][NH:19][C:3]=2[C:5]2[S:6][CH:7]=[CH:8][CH:9]=2)=[CH:11][CH:12]=1
null
ClC(Cl)Cl
O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
766,955
null
null
null
null
ord_dataset-7a8649d55889427e85b208ae89475895
2007-01-01T00:04:00
true
Cyclohexyl magnesium bromide (THF solution 1.0 M, 35 mL, 35 mmol) was added to a solution of 4-(4-methoxyphenyl)-1-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-on-5-yl)piperazine (1.00 g, 2.53 mmol) obtained in Reference Example 13 in THF (10 ml) under ice cooling and the reaction mixture was allowed to warm to room temperature. After stirring for one hour, the resulting mixture was poured into water and extracted with ethyl acetate. The organic extract was washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified with silica gel column chromatography (hexane/ethyl acetate=8/1) to obtain 970 mg (yield 80%) of the title compound via recrystallization (hexane). mp. 166–167° C.
COc1ccc(N2CCN(c3c(C)c(C)c4c(c3C)C(O)(C3CCCCC3)C(C)(C)O4)CC2)cc1
null
Br[Mg]C1CCCCC1
COc1ccc(N2CCN(c3c(C)c(C)c4c(c3C)C(=O)C(C)(C)O4)CC2)cc1
null
[CH:1]1([Mg]Br)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][N:20]([C:23]3[C:24]([CH3:37])=[C:25]([CH3:36])[C:26]4[O:30][C:29]([CH3:32])([CH3:31])[C:28](=[O:33])[C:27]=4[C:34]=3[CH3:35])[CH2:19][CH2:18]2)=[CH:13][CH:12]=1.O>C1COCC1>[CH:1]1([C:28]2([OH:33])[C:27]3[C:34]([CH3:35])=[C:23]([N:20]4[CH2:21][CH2:22][N:17]([C:14]5[CH:15]=[CH:16][C:11]([O:10][CH3:9])=[CH:12][CH:13]=5)[CH2:18][CH2:19]4)[C:24]([CH3:37])=[C:25]([CH3:36])[C:26]=3[O:30][C:29]2([CH3:31])[CH3:32])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
1
O
C1CCOC1
null
25
80.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,693,839
null
null
null
null
ord_dataset-c1e70ad912eb438f8d34b1dc681f809a
2016-01-01T00:02:00
true
From intermediate 21 and 2-(trifluoromethoxy)ethanamine, reacted in an analogous manner to the preparation of intermediate 102. (UPLC-MS 3) Rt=0.54 min; MS m/z [M+H]+ 247.
N#Cc1cnc(N)cc1NCCOC(F)(F)F
null
N#Cc1cnc(N)cc1F
NCCOC(F)(F)F
null
[NH2:1][C:2]1[CH:9]=[C:8](F)[C:5]([C:6]#[N:7])=[CH:4][N:3]=1.[F:11][C:12]([F:18])([F:17])[O:13][CH2:14][CH2:15][NH2:16]>>[NH2:1][C:2]1[CH:9]=[C:8]([NH:16][CH2:15][CH2:14][O:13][C:12]([F:18])([F:17])[F:11])[C:5]([C:6]#[N:7])=[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
1,596,244
[BH3-]C#N
[Na+]
[OH-]
null
ord_dataset-e8c6a25568b64529b960953990e6921f
2015-01-01T00:06:00
true
To a solution of (±)-2-(2-(5-methoxy-7-methyl-1H-indol-4-yl)pent-4-en-2-yl)-1H-benzo[d]imidazole-5-carbonitrile (Example 156-F) (150 mg, 0.405 mmol) in acetic acid (2.025 mL) was added sodium cyanoborohydride (38.2 mg, 0.607 mmol) and the reaction was stirred at room temperature for 1 hour. At this point the mixture was placed in an ice bath and quenched with NaOH (17.61 mL, 35.2 mmol) and then diluted with DCM. The layers were separated and the organic layer was dried over sodium sulfate, concentrated and absorbed onto silica and purified via FCC (0-100% EtOAc:heptanes) to give the title compound. MS (ESI+) m/z 373.3 (M+H).
C=CCC(C)(c1nc2cc(C#N)ccc2[nH]1)c1c(OC)cc(C)c2c1CCN2
null
C=CCC(C)(c1nc2cc(C#N)ccc2[nH]1)c1c(OC)cc(C)c2[nH]ccc12
null
null
[CH3:1][O:2][C:3]1[C:4]([C:13]([C:18]2[NH:22][C:21]3[CH:23]=[CH:24][C:25]([C:27]#[N:28])=[CH:26][C:20]=3[N:19]=2)([CH2:15][CH:16]=[CH2:17])[CH3:14])=[C:5]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[NH:8][CH:7]=[CH:6]2.C([BH3-])#N.[Na+].[OH-].[Na+]>C(O)(=O)C.C(Cl)Cl>[CH3:1][O:2][C:3]1[C:4]([C:13]([C:18]2[NH:22][C:21]3[CH:23]=[CH:24][C:25]([C:27]#[N:28])=[CH:26][C:20]=3[N:19]=2)([CH2:15][CH:16]=[CH2:17])[CH3:14])=[C:5]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[NH:8][CH2:7][CH2:6]2
1
CC(=O)O
ClCCl
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,605,399
[Na+]
[OH-]
null
null
ord_dataset-9cecb3a8d3b9494191b28dcefea66af2
2015-01-01T00:07:00
true
A mixture of Example 229D (0.16 g, 0.261 mmol) and 3N sodium hydroxide (0.261 mL, 0.784 mmol) in 1,4-dioxane (1.743 mL), ethanol (1.743 mL) and water (0.7 mL) was heated at 75° C. for 2.5 hours. The mixture was concentrated and the residue was partitioned in ethyl acetate and water. The organic layer was dried over sodium sulfate, filtered, and concentrated. Purification by flash chromatography on silica gel (AnaLogix IntelliFlash 280) eluting with a gradient of from 0-4% methanol in dichloromethane afforded the title compound. MS (ESI+) m/z 458.1 (M+H)+.
COc1ccc(F)cc1-c1c(Cl)cnc2[nH]c(C3=CCN(C(=O)OC(C)(C)C)CC3)cc12
null
COc1ccc(F)cc1-c1c(Cl)cnc2c1cc(C1=CCN(C(=O)OC(C)(C)C)CC1)n2S(=O)(=O)c1ccc(C)cc1
null
null
[Cl:1][C:2]1[C:3]([C:34]2[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=2[O:41][CH3:42])=[C:4]2[CH:10]=[C:9]([C:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]=3)[N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[OH-].[Na+]>O1CCOCC1.C(O)C.O>[Cl:1][C:2]1[C:3]([C:34]2[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=2[O:41][CH3:42])=[C:4]2[CH:10]=[C:9]([C:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1
null
CCO
O
C1COCCO1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,570,866
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
O=CO[O-]
[Na+]
null
ord_dataset-9741bb5fd93044078df2a45f45733054
2015-01-01T00:04:00
true
Compound number 247 (i.e., 6-chloro-5-(3,5-dichlorophenyl)-2-trifluoromethylbenzimidazole) was prepared as follows. A 100-mL round-bottom flask was purged and maintained with an inert atmosphere of nitrogen. 5-chloro-6-iodo-2-(trifluoromethyl)-1H-1,3-benzodiazole (200 mg, 0.58 mmol, 1.00 equiv), (3,5-dichlorophenyl)boronic acid (110 mg, 0.58 mmol, 2.00 equiv), dioxane (15 mL), Pd(PPh3)4 (66.8 mg, 0.06 mmol, 0.10 equiv), water (5 mL) and sodium methaneperoxoate sodium (183.8 mg, 1.72 mmol, 3.00 equiv) was placed in the flask. The resulting solution was stirred overnight at 100° C. in an oil bath. The reaction was then quenched by the addition of 15 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). The crude product (100 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-2): Column, C18 silica gel; mobile phase, water increasing to acetonitrile within 40 min; Detector, UV 254 nm. 47.7 mg product was obtained. This resulted in 47.7 mg (23%) of 6-chloro-5-(3,5-dichlorophenyl)-2-trifluoromethylbenzimidazole as a white solid.
FC(F)(F)c1nc2cc(Cl)c(-c3cc(Cl)cc(Cl)c3)cc2[nH]1
null
FC(F)(F)c1nc2cc(Cl)c(I)cc2[nH]1
OB(O)c1cc(Cl)cc(Cl)c1
null
[Cl:1][C:2]1[C:14](I)=[CH:13][C:5]2[NH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[N:8][C:4]=2[CH:3]=1.[Cl:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[C:21]([Cl:23])[CH:22]=1.O1CCOCC1.[Na+].C(O[O-])=O.[Na+].C(O[O-])=O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:1][C:2]1[C:14]([C:19]2[CH:18]=[C:17]([Cl:16])[CH:22]=[C:21]([Cl:23])[CH:20]=2)=[CH:13][C:5]2[NH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[N:8][C:4]=2[CH:3]=1
8
C1COCCO1
O
null
100
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
555,709
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
CN1C(=O)CC(=O)N(C)C1=O
On1nnc2ccccc21
null
ord_dataset-ec9decb576c4424c9685993f6262bd9c
2002-01-01T00:07:00
true
To a solution of 2-[6-(4-allyloxy-3,5-dichloro-benzoylamino)-2-methyl-3,7-dioxo-[1,2]diazepan-1-yl]-propionic acid (18) (183 mg, 0.40 mmol) in dichloromethane was added HOBT (65 mg, 0.48 mmol) followed by EDC (123 mg, 0.64 mmol). The mixture was stirred at 0° C. for 30 min, then a solution of (2-benzyloxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester (9, anti diastereomer) (140 mg, 0.48 mmol) in dichloromethane, charged with 1,3-dimethylbarbituric acid (DMBA) (75 mg, 0.48 mmol) and Pd(PPh3)4 (60 mg, 0.05 mmol) for 30 min, was added and the resulting mixture was stirred at room temperature for 5 hours. The second portion of DMBA (63 mg, 0.40 mmol) was added and the reaction mixture was continuously stirred at room temperature for 16 hours. The reaction was quenched with water and extracted with dichloromethane. The organic layer was dried over anhydrous Na2SO4, filtered and evaporated to give a pale yellow solid, that was purified by flash chromatography using dichloromethane/methanol (99/1 to 95/5) to afford 70 mg (29% yield) of the title compound as a mixture of diastereomers. 1H-NMR (500 MHz, CDCl3) δ 1.39-1.45 (m, 3H), 2.60-2.80 (m, 2H), 2.80-3.10 (m, 1H), 3.12-3.32 (m, 4H), 4.20-4.62 (m, 2H), 4.70-4.88 (m, 2H), 5.25-5.45 (m, 1H), 6.65-6.95 (m, 3H), 7.20-7.50 (m, 5H), 7.61 (s, 1H), 7.72 (d, 1H). Analytical HPLC: 10.86 and 10.98 min. LC-MS (ES+): m/e=607, 609 (M+H+).
CC(C(=O)NC1CC(=O)OC1OCc1ccccc1)N1C(=O)C(NC(=O)c2cc(Cl)c(O)c(Cl)c2)CCC(=O)N1C
null
C=CCOc1c(Cl)cc(C(=O)NC2CCC(=O)N(C)N(C(C)C(=O)O)C2=O)cc1Cl
C=CCOC(=O)NC1CC(=O)OC1OCc1ccccc1
null
C([O:4][C:5]1[C:28]([Cl:29])=[CH:27][C:8]([C:9]([NH:11][CH:12]2[C:18](=[O:19])[N:17]([CH:20](C)[C:21](O)=O)[N:16]([CH3:25])[C:15](=[O:26])[CH2:14][CH2:13]2)=[O:10])=[CH:7][C:6]=1[Cl:30])C=C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(O[C:49](=[O:65])[NH:50][CH:51]1[CH2:55][C:54](=[O:56])[O:53][CH:52]1[O:57][CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)C=C.CN1C(=O)CC(=O)N(C)C1=O>ClCCl.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>[CH2:58]([O:57][CH:52]1[CH:51]([NH:50][C:49]([CH:20]([N:17]2[C:18](=[O:19])[CH:12]([NH:11][C:9](=[O:10])[C:8]3[CH:27]=[C:28]([Cl:29])[C:5]([OH:4])=[C:6]([Cl:30])[CH:7]=3)[CH2:13][CH2:14][C:15](=[O:26])[N:16]2[CH3:25])[CH3:21])=[O:65])[CH2:55][C:54](=[O:56])[O:53]1)[C:59]1[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=1
0.5
ClCCl
ClCCCl
null
0
null
28.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
747,558
null
null
null
null
ord_dataset-4b705442211b4a3988e26d5f65098160
2006-01-01T00:12:00
true
To a solution of 2-{(4EZ)-5-[(4-{5-[(4-fluorophenyl)ethynyl]pyridin-2-yl}piperazin-1-yl)sulfonyl]pent-4-enyl}pyrimidine (760 mg, 1.55 mmol) in THF (10 mL) was added a solution of hydroxylamine (2 mL, 50% aqueous solution in water). The reaction was stirred for 2 hours at RT before being quenched with saturated aqueous ammonium chloride solution (5 mL). The layers were separated and the aqueous phase extracted with ethyl acetate (3×20 mL). The combined organic extracts were then dried, (MgSO4), filtered and concentrated in vacuo. The residue was then purified by bond elut (silica, EtOAc to 10% MeOH in ethyl acetate) to give 2-[5-[(4-{5-[(4-fluorophenyl)ethynyl]pyridin-2-yl}piperazin-1-yl)sulfonyl]-4-(hydroxyamino)pentyl]pyrimidine (518 mg, 0.99 mmol, 64%).
O=S(=O)(CC(CCCc1ncccn1)NO)N1CCN(c2ccc(C#Cc3ccc(F)cc3)cn2)CC1
null
NO
O=S(=O)(C=CCCCc1ncccn1)N1CCN(c2ccc(C#Cc3ccc(F)cc3)cn2)CC1
null
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[CH:11]=[CH:12][C:13]([N:16]3[CH2:21][CH2:20][N:19]([S:22]([CH:25]=[CH:26][CH2:27][CH2:28][CH2:29][C:30]4[N:35]=[CH:34][CH:33]=[CH:32][N:31]=4)(=[O:24])=[O:23])[CH2:18][CH2:17]3)=[N:14][CH:15]=2)=[CH:4][CH:3]=1.[NH2:36][OH:37]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[CH:11]=[CH:12][C:13]([N:16]3[CH2:17][CH2:18][N:19]([S:22]([CH2:25][CH:26]([NH:36][OH:37])[CH2:27][CH2:28][CH2:29][C:30]4[N:35]=[CH:34][CH:33]=[CH:32][N:31]=4)(=[O:24])=[O:23])[CH2:20][CH2:21]3)=[N:14][CH:15]=2)=[CH:4][CH:3]=1
2
C1CCOC1
null
null
25
64
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,127,570
Cl
null
null
null
ord_dataset-285df12e34cd46e993e3c8ebc3a8962a
2012-01-01T00:01:00
true
Chlorine gas was passed through a suspension of 230 g of ice, CH2Cl2 (457 ml) and methyl thioglycolate (86 ml, 942 mmol), cooling with an ice/water bath to maintain an internal temperature below 30° C. After approximately six hours, the yellow/green color of the dissolved chlorine persisted for 30 minutes after gas flow was stopped and passing additional chlorine gas was no longer exothermic. The cooling bath was then removed and the biphasic mixture was allowed to stir at ambient temperature for 1 h before being sparged with nitrogen for 20 minutes. The layers were then separated and the organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure to provide the intermediate methyl (chlorosulfonyl)acetate (160 g, 927 mmol) as a yellow oil. A portion of the intermediate methyl (chlorosulfonyl)acetate (100 g, 579 mmol) was added dropwise as a solution in CH2Cl2 (290 ml) to a stirring −15° C. solution of N-methylaniline (124 g, 1159 mmol) dissolved in CH2Cl2 (290 ml). The rate of addition was adjusted to maintain the internal temperature below 5° C. After the addition was complete, the reaction mixture was allowed to warm to room temperature over the course of 2 h and 1 M HCl (1000 mL) was added and the aqueous phase was extracted with dichloromethane (2×500 mL). The combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting oil was seed crystallized to afford a brown solid. Recrystallization from hot ethanol (320 mL) provided the title compound as an off-white solid. 1H NMR (600 MHz, DMSO-D6) δ 7.40 (m, 4H); 7.31 (m, 1H); 4.30 (s, 2H); 3.65 (s, 3H); 3.26 (s, 3H). LRMS (APCI) calculated for C25H21N4O3S [M+H]+, 244.1; found 244.0.
COC(=O)CS(=O)(=O)N(C)c1ccccc1
null
CNc1ccccc1
COC(=O)CS(=O)(=O)Cl
null
Cl[S:2]([CH2:5][C:6]([O:8][CH3:9])=[O:7])(=[O:4])=[O:3].[CH3:10][NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl>C(Cl)Cl>[CH3:10][N:11]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[S:2]([CH2:5][C:6]([O:8][CH3:9])=[O:7])(=[O:4])=[O:3]
null
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
null
1,760,184
[H-]
[Na+]
null
null
ord_dataset-97eb2ab57fec4160922caae33b54d956
2016-01-01T00:08:00
true
A solution of 2 ml (18.0 mmol) of (2,6-difluorophenyl)methanol in 15 ml of dry tetrahydrofuran stirred at 0° C. was admixed with 865.9 mg (21.6 mmol) of sodium hydride (60% in mineral oil), followed by 1.72 ml (18.0 mmol) of 2-bromopyridine. The resulting solution was stirred at room temperature for 15 h. The reaction mixture was diluted with water (15 ml) and extracted with dichloromethane (2×20 ml). The organic phase was removed, dried with a phase separation cartridge and concentrated under reduced pressure. The residue was purified by flash chromatography using a prepacked silica gel cartridge (eluent:cyclohexane-ethyl acetate 10:1 to 1:1), which gave 800 mg (15% of theory, 77% pure) of the target compound.
Fc1cccc(F)c1COc1ccccn1
null
OCc1c(F)cccc1F
Brc1ccccn1
null
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH2:9][OH:10].[H-].[Na+].Br[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1>O1CCCC1.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH2:9][O:10][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1
15
O
C1CCOC1
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
296,611
CC(=O)[O-]
[Na+]
null
null
ord_dataset-ec7cb3d5a8704f64b01d401ea555974f
1994-01-01T00:09:00
true
A mixture of 4,6-bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidine carboxaldehyde (1.00 g, 4.23 mmol), sodium acetate (1.36 g, 16.6 mmol), and 3-aminorhodanine (0.63 g, 4.3 mmol) in glacial acetic acid (15 mL), under nitrogen atmosphere, is warmed to reflux and refluxed 7 hours. This mixture is then cooled to room temperature and stirred 16 hours. After stirring, the reaction mixture is diluted with a 1:2 mixture of ethanol and water and extracted with ethyl acetate. The combined organic extracts are washed with water, aqueous 0.2N hydrochloric acid solution, and brine. The organic phase is dried over magnesium sulfate, concentrated, and purified by flash chromatography (SiO2, 20% ethyl acetate/hexane) followed by recrystallization from methanol and water to give 0.42 g (27%) of the title compound, mp 194°-196° C.
CC(C)(C)c1nc(C=C2SC(=S)N(N)C2=O)nc(C(C)(C)C)c1O
null
NN1C(=O)CSC1=S
CC(C)(C)c1nc(C=O)nc(C(C)(C)C)c1O
null
[CH3:1][C:2]([C:5]1[C:10]([OH:11])=[C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[N:8]=[C:7]([CH:16]=O)[N:6]=1)([CH3:4])[CH3:3].C([O-])(=O)C.[Na+].[NH2:23][N:24]1[C:28](=[O:29])[CH2:27][S:26][C:25]1=[S:30]>C(O)(=O)C.C(O)C.O>[CH3:1][C:2]([C:5]1[C:10]([OH:11])=[C:9]([C:12]([CH3:14])([CH3:15])[CH3:13])[N:8]=[C:7]([CH:16]=[C:27]2[S:26][C:25](=[S:30])[N:24]([NH2:23])[C:28]2=[O:29])[N:6]=1)([CH3:3])[CH3:4]
16
CC(=O)O
O
CCO
25
27.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,397,420
Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)(=Cc2ccccc2)[P](C2CCCCC2)(C2CCCCC2)C2CCCCC2)c(C)c1
Cl[Ru](Cl)(=Cc1ccccc1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1
null
null
ord_dataset-12dc3bd21bcf44d09e5b4249afe15161
2014-01-01T00:02:00
true
To a solution of but-3-enyl-(3-fluoro-6-nitro-2-vinylphenyl)amine (327.6 mg, 1.386 mmol) in DCM (30 mL) was added Grubbs catalyst (2nd generation, benzylidene[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(tricyclohexylphosphine)ruthenium) (47 mg, 0.055 mmol). The reaction mixture was stirred at RT for 16 h, and then a further portion of the Grubbs catalyst (47 mg, 0.055 mmol) was added and stirring continued for a further 64 h. The reaction mixture was concentrated in vacuo and then purified by column chromatography (Si—PCC, eluant 2-6% EtOAc in cyclohexane). The recovered starting material (145 mg) was dissolved in DCM (20 mL) and Grubbs 2nd generation catalyst (30 mg, 0.035 mmol) was added. The reaction mixture was heated under reflux for 6 h, then left at RT for 16 h. The reaction mixture was concentrated in vacuo, combined with the product from the initial purification and purified by column chromatography (Si—PCC, eluant 2-8% EtOAc in cyclohexane) affording the title compound as a red solid (225.4 mg, 78%). 1H NMR (CDCl3, 300 MHz): 8.90 (1H, bs), 8.09 (1H, dd, J=9.4, 6.0 Hz), 6.67 (1H, dt, J=12.3, 1.8 Hz), 6.47 (1H, t, J=9.6 Hz), 6.16 (1H, dt, J=12.3, 4.7 Hz), 3.52 (2H, q, J=4.9 Hz), 2.65 (2H, dq, J=4.8, 1.8 Hz)
O=[N+]([O-])c1ccc(F)c2c1NCCC=C2
null
C=CCCNc1c([N+](=O)[O-])ccc(F)c1C=C
null
null
[CH2:1]([NH:5][C:6]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][CH:9]=[C:8]([F:15])[C:7]=1[CH:16]=[CH2:17])[CH2:2]C=C>C(Cl)Cl.Cl[Ru](=CC1C=CC=CC=1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)Cl.Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1>[F:15][C:8]1[C:7]2[CH:16]=[CH:17][CH2:2][CH2:1][NH:5][C:6]=2[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][CH:9]=1
16
ClCCl
null
null
25
null
78.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,260,111
null
null
null
null
ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0
2013-01-01T00:02:00
true
The mixture of Wogonin (28.4 g), methanol (350 ml), 37% formaldehyde solution (8.1 ml), piperazine (8.6 g) was stirred under for 4 hours at 55° C., then precipitates were removed by filtration and washed several times with methanol, after drying under reduced pressure at 65° C. to get the product as yellow solid 36.1 g of purity 99.1%. MS: (API-ES) m/z 383.5[M+H]+; 1H NMR (DMSO-d6, 400 MHz) δ 8.13˜8.14 (m, 2H, Ar-2′,6′-H), 7.64˜7.66 (m, 3H, Ar-3′,4′,5′-H), 7.14 (s, 1H, 3-H), 4.43 (s, 2H, CH2), 3.98 (s, 3H, 8-OCH3), 3.36 (s, 4H, CH2), 3.56 (s, 4H, CH2), 1.25 (s, 1H, NH).
COc1c(O)c(CN2CCNCC2)c(O)c2c(=O)cc(-c3ccccc3)oc12
null
C1CNCCN1
C=O
COc1c(O)cc(O)c2c(=O)cc(-c3ccccc3)oc12
[CH3:1][O:2][C:3]1[C:4]([OH:21])=[CH:5][C:6]([OH:20])=[C:7]2[C:12](=[O:13])[CH:11]=[C:10]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[O:9][C:8]=12.[CH2:22]=O.[NH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>CO>[OH:20][C:6]1[C:5]([CH2:22][N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[C:4]([OH:21])[C:3]([O:2][CH3:1])=[C:8]2[C:7]=1[C:12](=[O:13])[CH:11]=[C:10]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[O:9]2
4
CO
null
null
55
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
630,484
Cl
O=C([O-])[O-]
null
null
ord_dataset-0a66204fc43e49c2922e6f9107e6b62f
2004-01-01T00:03:00
true
Prepared analogously to Example 25d from 1-methyl-2-[N-(4-cyano-2-ethylphenyl)aminomethyl]benzimidazol-5-yl-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)amide, ethanolic hydrochloric acid, ethanol, and ammonium carbonate. Yield: 61% of theory, C30H34N6O3 (526.6); EKA mass spectrum: (M+H)+=527; (M+H+Na)++=275; (M+2H)++=264.
CCOC(=O)CCN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C(=N)N)cc1CC)n2C)c1ccccc1
null
CCOC(=O)CCN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C#N)cc1CC)n2C)c1ccccc1
[NH4+]
null
[C:1]1([N:7]([CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:8]([C:10]2[CH:31]=[CH:30][C:13]3[N:14]([CH3:29])[C:15]([CH2:17][NH:18][C:19]4[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[CH:21][C:20]=4[CH2:27][CH3:28])=[N:16][C:12]=3[CH:11]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:39].C(=O)([O-])[O-].[NH4+:44].[NH4+]>C(O)C>[ClH:39].[C:1]1([N:7]([CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:8]([C:10]2[CH:31]=[CH:30][C:13]3[N:14]([CH3:29])[C:15]([CH2:17][NH:18][C:19]4[CH:24]=[CH:23][C:22]([C:25](=[NH:44])[NH2:26])=[CH:21][C:20]=4[CH2:27][CH3:28])=[N:16][C:12]=3[CH:11]=2)=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
null
CCO
null
null
null
61
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
743,855
null
null
null
null
ord_dataset-437aa6654d5044ddaef3346dc4c6e08a
2006-01-01T00:11:00
true
To a stirred solution of N-{[(2-{4-[(3-amino-4,6-dimethyl-2-pyridinyl)amino]phenyl}ethyl)amino]carbonyl}-4-methylbenzenesulfonamide (300 mg, 0.66 mmol) in THF (6 ml) was added a solution of BrCN (175 mg, 1.65 mmol) in water (2 ml). The resultant mixture was stirred at room temperature for 16 hours. The mixture was diluted with CH2Cl2 and washed with brine. The organic layer was dried over MgSO4 and filtered. After concentration in vacuo, the residue was purified by preparative TLC (CH2Cl2/MeOH=10/1) to afford 224 mg (71%) of the title compound.
Cc1ccc(S(=O)(=O)NC(=O)NCCc2ccc(-n3c(N)nc4c(C)cc(C)nc43)cc2)cc1
null
N#CBr
Cc1ccc(S(=O)(=O)NC(=O)NCCc2ccc(Nc3nc(C)cc(C)c3N)cc2)cc1
null
[NH2:1][C:2]1[C:3]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][NH:19][C:20]([NH:22][S:23]([C:26]3[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=3)(=[O:25])=[O:24])=[O:21])=[CH:13][CH:12]=2)=[N:4][C:5]([CH3:9])=[CH:6][C:7]=1[CH3:8].Br[C:34]#[N:35]>C1COCC1.O.C(Cl)Cl>[NH2:35][C:34]1[N:10]([C:11]2[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][NH:19][C:20]([NH:22][S:23]([C:26]3[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=3)(=[O:25])=[O:24])=[O:21])=[CH:13][CH:12]=2)[C:3]2=[N:4][C:5]([CH3:9])=[CH:6][C:7]([CH3:8])=[C:2]2[N:1]=1
null
C1CCOC1
ClCCl
O
null
70.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
498,041
null
null
null
null
ord_dataset-18e9ed24dbd44e98b33bdc22aa7580a8
2001-01-01T00:04:00
true
In substantially the same manner as in Working Example 109, 1-[4-(4-hydroxyphenyl)butyl]imidazole was allowed to react with 2-(4-benzoylphenyl)-4-chloromethyloxazole to give 2-(4-benzoylphenyl)-4-[4-[4-(1-imidazolyl)butyl]phenoxymethyl]oxazole. The yield was 64%. Recrystallization from ethyl acetate-hexane gave colorless prisms, mp 91-92° C.
O=C(c1ccccc1)c1ccc(-c2nc(COc3ccc(CCCCn4ccnc4)cc3)co2)cc1
null
O=C(c1ccccc1)c1ccc(-c2nc(CCl)co2)cc1
Oc1ccc(CCCCn2ccnc2)cc1
null
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][N:12]2[CH:16]=[CH:15][N:14]=[CH:13]2)=[CH:4][CH:3]=1.[C:17]([C:25]1[CH:30]=[CH:29][C:28]([C:31]2[O:32][CH:33]=[C:34]([CH2:36]Cl)[N:35]=2)=[CH:27][CH:26]=1)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[C:17]([C:25]1[CH:30]=[CH:29][C:28]([C:31]2[O:32][CH:33]=[C:34]([CH2:36][O:1][C:2]3[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][N:12]4[CH:16]=[CH:15][N:14]=[CH:13]4)=[CH:4][CH:3]=3)[N:35]=2)=[CH:27][CH:26]=1)(=[O:24])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
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
1,125,202
Cl[Ni]Cl
[BH4-]
[Na+]
null
ord_dataset-285df12e34cd46e993e3c8ebc3a8962a
2012-01-01T00:01:00
true
NaBH4 (2.64 g, 69.8 mmol) was added carefully in portions to a suspension of 1-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-4-[2-(methylsulfonyl)-ethyl]piperazine (9.9 g, 23.3 mmol), nickel(II)chloride hexahydrate (1.66 g, 7 mmol), MeOH (120 mL) and THF (60 mL) at 0° C. The ice bath was removed and the reaction mixture was stirred at rt overnight (˜16 h). The reaction mixture was concentrated onto silica gel and flash chromatography afforded the title compound of step B (6.24 g, 68%) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ 6.49-6.44 (m, 2H), 6.26 (dd, J=8.4, 2.6 Hz, 1H), 4.18 (bs, 2H), 3.71 (s, 3H), 3.43-3.36 (m, 2H), 3.25 (t, J=6.8 Hz, 2H), 3.00 (s, 3H), 2.65 (t, J=6.8 Hz, 2H), 2.47-2.36 (m, 4H), 2.23-2.15 (m, 1H), 1.82-1.75 (m, 2H), 1.54-1.43 (m, 2H).
COc1cc(N2CCC(N3CCN(CCS(C)(=O)=O)CC3)CC2)ccc1N
null
COc1cc(N2CCC(N3CCN(CCS(C)(=O)=O)CC3)CC2)ccc1[N+](=O)[O-]
null
null
[BH4-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([N:14]2[CH2:19][CH2:18][CH:17]([N:20]3[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH2:22][CH2:21]3)[CH2:16][CH2:15]2)[CH:8]=[CH:9][C:10]=1[N+:11]([O-])=O.CO>O.O.O.O.O.O.[Ni](Cl)Cl.C1COCC1>[CH3:3][O:4][C:5]1[CH:6]=[C:7]([N:14]2[CH2:15][CH2:16][CH:17]([N:20]3[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][S:28]([CH3:31])(=[O:29])=[O:30])[CH2:24][CH2:25]3)[CH2:18][CH2:19]2)[CH:8]=[CH:9][C:10]=1[NH2:11]
16
CO
O
C1CCOC1
25
null
67.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
237,849
CC(C)(C#N)N=NC(C)(C)C#N
O=C(OOC(=O)c1ccccc1)c1ccccc1
null
null
ord_dataset-56e7a343b17a4d6da818127ceb19589d
1991-01-01T00:11:00
true
A slurry of 1,1-bis(4-fluorophenyl)-2-(1-methyl-1H-tetrazol-5-yl)-1-propene (61.46 g, 0.197 mole) [prepared in Step C], N-bromosuccinamide (35.06 g, 0.197 mole) and catalytic amount of azobis isobutyronitrile or benzoyl peroxide in carbon tetrachloride (1.2 liters) was heated to reflux in an inert atmosphere for a period of 2 hours. The reaction mixture was cooled to ambient temperature and the solid from the reaction was filtered. The filtrate was concentrated under reduced pressure and the solid obtained was recrystallized from toluene-hexane to give 72 g (93%) of the title compound as white crystals; m.p.=159°-160° C.
Cn1nnnc1C(CBr)=C(c1ccc(F)cc1)c1ccc(F)cc1
null
NC(=O)CCC(=O)NBr
CC(=C(c1ccc(F)cc1)c1ccc(F)cc1)c1nnnn1C
null
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[C:9]([C:11]2[N:15]([CH3:16])[N:14]=[N:13][N:12]=2)[CH3:10])=[CH:4][CH:3]=1.[Br:24]NC(=O)CCC(N)=O.N(C(C)(C)C#N)=NC(C)(C)C#N.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:17]2[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=2)=[C:9]([C:11]2[N:15]([CH3:16])[N:14]=[N:13][N:12]=2)[CH2:10][Br:24])=[CH:4][CH:3]=1
null
ClC(Cl)(Cl)Cl
null
null
25
null
93.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,626,706
null
null
null
null
ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d
2015-01-01T00:09:00
true
Following general procedure D, {6-bromo-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]quinolin-3-yl}(cyclopropyl)methanone (102 mg, 0.225 mmol was reacted with 2-chloro-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (42 mg, 0.150 mmol) to afford the desired product (16.8 mg, 48%) as an orange-brown solid: 1H NMR (500 MHz, CD3OD) δ 8.76 (2, 1H), 8.30 (d, J=1.4 Hz, 1H), 8.08-8.00 (m, 2H), 7.33 (d, 0.1=2.1 Hz, 1H), 7.26 (d, J=2.0 Hz, 1H), 4.00 (s, 3H), 3.57 (d, J=12.9 Hz, 2H), 3.34 (s, 3H), 3.24-3.16 (m, 2H), 2.79-2.52 (m, 7H), 2.36 (s, 3H), 2.11 (d, J=11.3 Hz, 2H), 1.96-1.83 (m, 2H), 1.34-1.28 (m, 2H), 126-1.19 (m, 2H); ESI MS m/z 535 [C30H35ClN4O3+H]+; HPLC>99% (AUC), tR=10.13 min.
COc1cc(-c2ccc3ncc(C(=O)C4CC4)c(N4CCC(N5CCN(C)CC5)CC4)c3c2)cc(Cl)c1O
null
CN1CCN(C2CCN(c3c(C(=O)C4CC4)cnc4ccc(Br)cc34)CC2)CC1
COc1cc(B2OC(C)(C)C(C)(C)O2)cc(Cl)c1O
null
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([CH:14]1[CH2:16][CH2:15]1)=[O:13])=[C:5]2[N:17]1[CH2:22][CH2:21][CH:20]([N:23]2[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]2)[CH2:19][CH2:18]1.[Cl:30][C:31]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[C:33]([O:46][CH3:47])[C:32]=1[OH:48]>>[Cl:30][C:31]1[CH:36]=[C:35]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][C:6]([C:12]([CH:14]2[CH2:15][CH2:16]2)=[O:13])=[C:5]3[N:17]2[CH2:18][CH2:19][CH:20]([N:23]3[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH2:28]3)[CH2:21][CH2:22]2)[CH:34]=[C:33]([O:46][CH3:47])[C:32]=1[OH:48]
null
null
null
null
null
48
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
100,631
null
null
null
null
ord_dataset-e984b2d4813f44d59867e1771acc9b66
1982-01-01T00:11:00
true
A 100-ml stainless steel-lined tube charged with 38.5 g (0.14 mol) of perfluoro-4-oxa-6-heptenenitrile was heated at 140° while oxygen was added incrementally (over 5.5 h) until reaction was complete. Fractionation of the liquid products gave perfluoro-6,7-epoxy-4-oxaheptanenitrile, bp 65°-67°, 15.7 g (39%). IR (CCl4); 4.40 (CN), 6.47 (epoxide) and 8-9μ (CF, C-O). NMR (CCl4): -87.5 (m, 2F, OCF2), -109.2 (t, JFF 4.7 Hz, 2F, CF2CN), and -156.7 ppm (d of d of m, JFF 18.7, 16.7 Hz, 1F, CF) with AB groupings for ring CF2 at -10347 and -10389 Hz (d of t, JFF 18.7, 9.5 Hz, 1F) and -10570 and -10610 Hz (d, JFF 16.7 Hz, 1F) and for CF 2 adjacent to epoxide ring at -7376, -7529, -7556, and -7707 Hz (m, 2F).
N#CC(F)(F)C(F)(F)OC(F)(F)C1(F)OC1(F)F
null
N#CC(F)(F)C(F)(F)OC(F)(F)C(F)=C(F)F
O=O
null
[F:1][C:2]([F:17])([C:5]([F:16])([F:15])[O:6][C:7]([F:14])([F:13])[C:8]([F:12])=[C:9]([F:11])[F:10])[C:3]#[N:4].[O:18]=O>>[F:1][C:2]([F:17])([C:5]([F:15])([F:16])[O:6][C:7]([F:14])([F:13])[C:8]1([F:12])[O:18][C:9]1([F:11])[F:10])[C:3]#[N: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
716,723
CN(C)C(On1nnc2ccccc21)=[N+](C)C
F[P-](F)(F)(F)(F)F
null
null
ord_dataset-c8a367b56b4f406b878f51867b157d19
2006-01-01T00:06:00
true
To a solution of 1-(3-carboxymethoxybenzoyl)-6,7-dimethoxy-isoquinoline-4-carboxylic acid ethyl ester (103.5 mg, 0.22 mmol) in 8 ml of methylene chloride was added 1.0 equivalent of N-benzylpiperazine, 1.05 equivalent of HBTU and 4 equivalent of triethylamine. The mixture was stirred at room temperature overnight. The solvents were evaporated and the residue was extracted with ethyl acetate and water. The organic phase was dried and solvents were evaporated. The residue was dissolved in 4 ml of methanol and aqueous lithium hydroxide was added (0.5N, 1 ml). The mixture was stirred overnight until all starting material disappeared. The reaction was loaded on a preparative HPLC for purification to give 1-{3-[2-(4-Benzyl-piperazin-1-yl)-2-oxo-ethoxy]-benzoyl}-6,7-dimethoxy-isoquinoline-4-carboxylic acid as a fluffy solid (43 mg, 35%). ES-MS calcd for C32H31N3O7 (m/e) 569.6, obsd 570.3 (M+H).
COc1cc2c(C(=O)O)cnc(C(=O)c3cccc(OCC(=O)N4CCN(Cc5ccccc5)CC4)c3)c2cc1OC
null
CCOC(=O)c1cnc(C(=O)c2cccc(OCC(=O)O)c2)c2cc(OC)c(OC)cc12
c1ccc(CN2CCNCC2)cc1
null
C([O:3][C:4]([C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=2)[C:9]([C:20](=[O:32])[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH2:28][C:29]([OH:31])=O)[CH:22]=2)=[N:8][CH:7]=1)=[O:5])C.[CH2:33]([N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(Cl)Cl>[CH2:33]([N:40]1[CH2:45][CH2:44][N:43]([C:29](=[O:31])[CH2:28][O:27][C:23]2[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=2)[C:20]([C:9]2[C:10]3[C:15](=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=3)[C:6]([C:4]([OH:3])=[O:5])=[CH:7][N:8]=2)=[O:32])[CH2:42][CH2:41]1)[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1
8
ClCCl
CCN(CC)CC
null
25
35
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
332,038
Cl
null
null
null
ord_dataset-1558660634294cc8ad7e01746e9083fd
1996-01-01T00:06:00
true
The procedure of Example 3(iv) was followed using 5-(2-chloro)ethyl-1-[(2-chlorophenyl)methyl]-2-propylthio-1H-imidazole hydrochloride in place of 5-chloromethyl-1-[(2-chlorophenyl)methyl]2-propylthio-1H-imidazole hydrochloride. The title compound was obtained in 71% yield after chromatography over silica gel with a gradient of ethyl acetate in methylene chloride.
CCCSc1ncc(CCC(C(=O)OCC)C(=O)OCC)n1Cc1ccccc1Cl
null
CCCSc1ncc(CCCl)n1Cc1ccccc1Cl
CCOC(C)=O
null
Cl.Cl[CH2:3][CH2:4][C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])[C:8]([S:18][CH2:19][CH2:20][CH3:21])=[N:7][CH:6]=1.[C:22]([O:25][CH2:26][CH3:27])(=[O:24])[CH3:23]>C(Cl)Cl>[Cl:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[CH2:10][N:9]1[C:5]([CH2:4][CH2:3][CH:23]([C:22]([O:25][CH2:26][CH3:27])=[O:24])[C:22]([O:25][CH2:26][CH3:27])=[O:24])=[CH:6][N:7]=[C:8]1[S:18][CH2:19][CH2:20][CH3:21]
null
ClCCl
null
null
null
71
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,386,748
CN(C)C(=N)N(C)C
null
null
null
ord_dataset-31641fb65b34430fa7435229b949b604
2014-01-01T00:01:00
true
Prepared as in Example 274c (except DBU was replaced with 1,1,3,3-tetramethylguanidine) from 1,9-nonanediol and 2,6-dinitrobenzonitrile in 30.7% yield. MS 307 (MH+).
N#Cc1c(OCCCCCCCCCO)cccc1[N+](=O)[O-]
null
OCCCCCCCCCO
N#Cc1c([N+](=O)[O-])cccc1[N+](=O)[O-]
null
C1CCN2C(=NCCC2)CC1.CN(C)C(N(C)C)=N.[CH2:20]([OH:30])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][OH:29].[N+:31]([C:34]1[CH:41]=[CH:40][CH:39]=[C:38]([N+]([O-])=O)[C:35]=1[C:36]#[N:37])([O-:33])=[O:32]>>[OH:30][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][O:29][C:38]1[CH:39]=[CH:40][CH:41]=[C:34]([N+:31]([O-:33])=[O:32])[C:35]=1[C:36]#[N:37]
null
C1CCC2=NCCCN2CC1
null
null
null
30.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
280,488
Cl
[Na+]
[OH-]
null
ord_dataset-140fb5527ff24f97bcf0094c5d100120
1993-01-01T00:11:00
true
2-t-butyl-4-t-octylphenol (140 g, 0.53 mole) was dissolved in 420 ml of absolute ethanol in a 3 L round bottom flask equipped with a water-cooled condenser. Sodium hydroxide (213 g, 5.3 moles) was dissolved in 200 ml water and added while still hot to the solution of phenol. Chloroform (127 g, 1.06 mole) was added in 2 to 3 ml portions over a 1 hour period. The resulting yellow-brown mixture was stirred for 1 hour while it cooled to ambient temperature. The mixture was diluted into 500 ml of 5M hydrochloric acid. The organic layer was isolated in a separatory funnel and dried over anhydrous magnesium sulfate. The mixture was filtered and rotoevaporated to a thick syrup to yield 26% crude product with an IR spectrum having the characteristic aldehyde carbonyl stretching frequency. The product was used without further purification.
CC(C)(C)CC(C)(C)c1cc(C=O)c(O)c(C(C)(C)C)c1
null
Oc1ccccc1
CC(C)(C)CC(C)(C)c1ccc(O)c(C(C)(C)C)c1
null
[C:1]([C:5]1[CH:10]=[C:9]([C:11]([CH2:14][C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:13])[CH3:12])[CH:8]=[CH:7][C:6]=1[OH:19])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[C:22]1([OH:28])C=CC=CC=1.C(Cl)(Cl)Cl.Cl>C(O)C.O>[C:1]([C:5]1[CH:10]=[C:9]([C:11]([CH2:14][C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:13])[CH3:12])[CH:8]=[C:7]([CH:22]=[O:28])[C:6]=1[OH:19])([CH3:4])([CH3:3])[CH3:2]
1
CCO
ClC(Cl)Cl
O
25
null
26
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
898,664
null
null
null
null
ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded
2009-01-01T00:08:00
true
N-[6-(6,7-Dimethoxyquinazolin-4-ylamino)benzothiazol-2-yl]isonicotinamide was prepared by heating a mixture of N-(6-aminobenzothiazol-2-yl)isonicotinamide Intermediate 3, 50 mg, 0.185 mmol) and 4-chloro-6,7-dimethoxyquinazoline (Fluorochem, 42 mg, 0.185 mmol in ethanol (3 mL) to 80° C. for 2 h. The resulting precipitate was separated by filtration, washed with ethanol and dried (yellow solid, 82 mg, 0.179 mmol, 97%). LC/ESI-MS: m/z 459 [M+H]+; m/z=457 [M−H]−; Rt=2.65 min.
COc1cc2ncnc(Nc3ccc4nc(NC(=O)c5ccncc5)sc4c3)c2cc1OC
null
Nc1ccc2nc(NC(=O)c3ccncc3)sc2c1
COc1cc2ncnc(Cl)c2cc1OC
null
[NH2:1][C:2]1[CH:19]=[CH:18][C:5]2[N:6]=[C:7]([NH:9][C:10](=[O:17])[C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)[S:8][C:4]=2[CH:3]=1.Cl[C:21]1[C:30]2[C:25](=[CH:26][C:27]([O:33][CH3:34])=[C:28]([O:31][CH3:32])[CH:29]=2)[N:24]=[CH:23][N:22]=1>C(O)C>[CH3:32][O:31][C:28]1[CH:29]=[C:30]2[C:25](=[CH:26][C:27]=1[O:33][CH3:34])[N:24]=[CH:23][N:22]=[C:21]2[NH:1][C:2]1[CH:19]=[CH:18][C:5]2[N:6]=[C:7]([NH:9][C:10](=[O:17])[C:11]3[CH:12]=[CH:13][N:14]=[CH:15][CH:16]=3)[S:8][C:4]=2[CH:3]=1
null
CCO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,706,404
Br
null
null
null
ord_dataset-54347fcace774f89850681d6dec8009f
2016-01-01T00:03:00
true
500 mg (1.53 mmol) of the compound of Example 1A is reacted analogously to the synthesis of the compound of Example 20A with 342 mg (1.68 mmol) of 2-methylpyridin-4-yl-hydrazine hydrobromide. After hydrolysis, 425 mg (84% of theory) of the title compound is obtained.
Cc1cc(-n2nc(C(=O)O)cc2-c2cc(F)cc(Cl)c2)ccn1
null
O=C(O)c1cc(-c2cc(F)cc(Cl)c2)n(-c2ccccn2)n1
Cc1cc(NN)ccn1
null
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][CH:17]=CN=3)[N:12]=[C:11]([C:20]([OH:22])=[O:21])[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.Br.[CH3:24][C:25]1C=C(NN)C=C[N:26]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]([C:14]3[CH:24]=[CH:25][N:26]=[C:18]([CH3:17])[CH:19]=3)[N:12]=[C:11]([C:20]([OH:22])=[O:21])[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,592,966
Cl
[H-]
[Na+]
null
ord_dataset-e8c6a25568b64529b960953990e6921f
2015-01-01T00:06:00
true
To a stirred solution of (4-(4-chlorophenoxy)piperidin-1-yl)(1H-indol-5-yl)methanone (30 mg, 0.085 mmol, Step-1) and sodium hydride (60% in oil, 6 mg, 0.25 mmol) in N,N-dimethylformamide (1.5 mL) was added 4-(2-chloroethyl)morpholine hydrochloride (35 mg, 0.19 mmol) at room temperature. Then the mixture was stirred at 70° C. for 2 hours. The mixture was poured into water (20 mL) and extracted with ethyl acetate (20 mL). The organic layer was washed with water (20 mL), and dried over sodium sulfate. After removal of the solvent, the residue was purified by silica-gel column chromatography (NH-gel, eluting with ethyl acetate) and then preparative LC-MS to give 11.9 mg (30% yield) of the title compound.
O=C(c1ccc2c(ccn2CCN2CCOCC2)c1)N1CCC(Oc2ccc(Cl)cc2)CC1
null
O=C(c1ccc2[nH]ccc2c1)N1CCC(Oc2ccc(Cl)cc2)CC1
ClCCN1CCOCC1
null
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([O:6][CH:7]2[CH2:12][CH2:11][N:10]([C:13]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[NH:20][CH:19]=[CH:18]4)=[O:14])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl.Cl[CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.O>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH:7]2[CH2:12][CH2:11][N:10]([C:13]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[N:20]([CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[CH:19]=[CH:18]4)=[O:14])[CH2:9][CH2:8]2)=[CH:24][CH:25]=1
2
CN(C)C=O
O
null
70
null
29.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,262,060
null
null
null
null
ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0
2013-01-01T00:02:00
true
A vial equipped with a flea stirbar was charged with (±)-(E)-1-(3-amino-7-bromo-2,3-dihydrospiro[indene-1,4′-piperidine]-1′-yl)-3-(2-(trifluoromethyl)phenyl)prop-2-en-1-one TFA salt (9 mg, 0.015 mmol), i-Pr2NEt (0.01 mL) and CH2Cl2 (1 mL). MeNCO (0.05 mL, 0.085 mmol) was added. The mixture was stirred at rt for 3 h and evaporated to dryness. The residue was purified by prep HPLC to afford (±)-(E)-1-(7-bromo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)-3-methylurea (2.9 mg, 59%). LC-MS Method 1 tR=1.77, min, m/z=536, 538.
CNC(=O)NC1CC2(CCN(C(=O)/C=C/c3ccccc3C(F)(F)F)CC2)c2c(Br)cccc21
null
CN=C=O
NC1CC2(CCN(C(=O)/C=C/c3ccccc3C(F)(F)F)CC2)c2c(Br)cccc21
null
OC(C(F)(F)F)=O.[NH2:8][CH:9]1[C:36]2[C:31](=[C:32]([Br:37])[CH:33]=[CH:34][CH:35]=2)[C:11]2([CH2:16][CH2:15][N:14]([C:17](=[O:30])/[CH:18]=[CH:19]/[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:29])([F:28])[F:27])[CH2:13][CH2:12]2)[CH2:10]1.CCN(C(C)C)C(C)C.[CH3:47][N:48]=[C:49]=[O:50]>C(Cl)Cl>[Br:37][C:32]1[CH:33]=[CH:34][CH:35]=[C:36]2[C:31]=1[C:11]1([CH2:16][CH2:15][N:14]([C:17](=[O:30])/[CH:18]=[CH:19]/[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:27])([F:28])[F:29])[CH2:13][CH2:12]1)[CH2:10][CH:9]2[NH:8][C:49]([NH:48][CH3:47])=[O:50]
3
CCN(C(C)C)C(C)C
ClCCl
O=C(O)C(F)(F)F
25
36
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
430,724
CCOC(=O)N=NC(=O)OCC
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
null
ord_dataset-2d21ceeb77844edc9eaedb2fabca2ff1
1999-01-01T00:04:00
true
To 458 mg (1.49 mmol) 3-(2-methoxy-5-methylphenylsulfonyloxy)-5-methylphenol, as prepared in the preceding step, 1.08 mL (14.9 mmol) of 1,3-propanediol and 782 mg (2.98 mmol) of triphenylphosphine in 10 mL of anhydrous tetrahydrofuran was added 0.470 mL (2.98 mmol) of diethyl azodicarboxylate dropwise over 15 min. After stirring at ambient temperature for 2 h, the reaction mixture was concentrated to a semisolid. The resulting mixture was flash chromatographed on 50 g of silica gel with 8-10% ethyl acetate-dichloromethane. Impure fractions were re-chromatographed on 40 g of silica gel with 50-100% ethyl acetate-hexane. Material from the two purifications was combined to afford 530 mg (97% yield) of the title compound as a colorless oil: 1H-NMR (300 MHz; CDCl3) δ 7.95 (d, 1 H, J=2.2 Hz), 7.40 (dd, 1 H, J=8.5, 2.3 Hz), 6.97 (d, 1 H, J=8.5 Hz), 6.59 (br s, 1 H), 6.53 (br s, 1 H), 6.47 (t, 1 H, J=2.1 Hz), 4.01 (t, 2 H, J=6.0 Hz), 3.98 (s, 3 H), 3.81 (q, 2 H, J=5.7 Hz), 2.29 (s, 3 H), 2.25 (s, 3 H) and 1.98 (m, 2 H).
COc1ccc(C)cc1S(=O)(=O)Oc1cc(C)cc(OCCCO)c1
null
OCCCO
COc1ccc(C)cc1S(=O)(=O)Oc1cc(C)cc(O)c1
null
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][C:4]=1[S:10]([O:13][C:14]1[CH:15]=[C:16]([OH:21])[CH:17]=[C:18]([CH3:20])[CH:19]=1)(=[O:12])=[O:11].[CH2:22](O)[CH2:23][CH2:24][OH:25].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][C:4]=1[S:10]([O:13][C:14]1[CH:15]=[C:16]([CH:17]=[C:18]([CH3:20])[CH:19]=1)[O:21][CH2:22][CH2:23][CH2:24][OH:25])(=[O:11])=[O:12]
2
C1CCOC1
null
null
25
null
97.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,016,459
null
null
null
null
ord_dataset-f024e9664ab64906a71a2ff6004cb3d0
2010-01-01T00:12:00
true
In a manner analogous to the method described in example 5, rac-(4S*,5R*)-4,5-bis-(4-chloro-phenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride was reacted with 1-(2-methanesulfonyl-ethyl)-piperazine (prepared as described in Fotouhi, N. et al. WO 2005110996) to give the title compound. HR-MS (ES, m/z) calculated for C35H43N4O5SCl2 [(M+H)+] 701.2326, observed 701.2325.
COc1ccc(C2=N[C@@](C)(c3ccc(Cl)cc3)[C@@](C)(c3ccc(Cl)cc3)N2C(=O)N2CCN(CCS(C)(=O)=O)CC2)c(OC(C)C)c1
null
CS(=O)(=O)CCN1CCNCC1
COc1ccc(C2=NC(C)(c3ccc(Cl)cc3)C(C)(c3ccc(Cl)cc3)N2C(=O)Cl)c(OC(C)C)c1
null
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH3:36])[C:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH3:13])[N:11]([C:21](Cl)=[O:22])[C:10]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=3[O:32][CH:33]([CH3:35])[CH3:34])=[N:9]2)=[CH:4][CH:3]=1.[CH3:37][S:38]([CH2:41][CH2:42][N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)(=[O:40])=[O:39]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]2([CH3:36])[C@:12]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)([CH3:13])[N:11]([C:21]([N:46]3[CH2:45][CH2:44][N:43]([CH2:42][CH2:41][S:38]([CH3:37])(=[O:39])=[O:40])[CH2:48][CH2:47]3)=[O:22])[C:10]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=3[O:32][CH:33]([CH3:35])[CH3:34])=[N:9]2)=[CH:6][CH:7]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,515,578
[Cu]I
CCCC[N+](CCCC)(CCCC)CCCC
[OH-]
null
ord_dataset-8c74302143c04eb9983e4b3a7ead2d72
2014-01-01T00:12:00
true
A mixture of (S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.05 g, 0.099 mmol) (as prepared in Ex. 3, Part A), tetra-N-butylammonium hydroxide. 30H2O (0.463 g, 1.784 mmol) and water (1.5 mL) was added over 0.1 h to a stirred solution of copper(I) iodide (1.89 mg, 9.91 μmol) and 2-methyl 8-quinolinol (3.16 mg, 0.020 mmol) in DMSO (1 mL). The reaction mixture was heated to 120° C. and stirred for 14 h. The resulting mixture was cooled to room temperature. The crude product was purified by reverse phase HPLC (10 mM ammonium acetate) to afford a (S)-8-((2-amino-4-methylpentyl)oxy)-9-hydroxy-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (0.004 g, 0.011 mmol, 12% yield) as a brown solid. LC/MS (ESI) m/e 342.2 [(M+H)+, calcd for C19H24N3O3, 342.2]; HPLC retention time (method F): tR=1.62 min. HPLC retention time (method B): tR=5.88 min. 1H NMR (400 MHz, CD3OD) δ 9.39 (s, 1H), 8.62 (d, J=6.00 Hz, 1H), 7.96 (d, J=5.60 Hz, 1H), 7.56 (s, 1H), 6.73 (s, 1H), 3.80 (s, 3H), 3.67-3.70 (m, 1H), 3.49-3.59 (m, 2H), 1.81-1.85 (m, 1H), 1.56-1.63 (m, 2H), 1.05 (d, J=6.80 Hz, 3H), 0.98 (d, J=6.80 Hz, 3H).
CC(C)C[C@H](N)COc1cc2c(cc1O)c1ccncc1c(=O)n2C
null
CC(C)C[C@@H](COc1cc2c(cc1Br)c1ccncc1c(=O)n2C)NC(=O)OC(C)(C)C
Cc1ccc2cccc(O)c2n1
null
Br[C:2]1[C:17]([O:18][CH2:19][C@@H:20]([NH:25]C(=O)OC(C)(C)C)[CH2:21][CH:22]([CH3:24])[CH3:23])=[CH:16][C:5]2[N:6]([CH3:15])[C:7](=[O:14])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][CH:9]=3.CCCC[N+](CCCC)(CCCC)CCCC.[OH-].O.CC1C=CC2C(=C([OH:63])C=CC=2)N=1>CS(C)=O.[Cu]I>[NH2:25][C@@H:20]([CH2:21][CH:22]([CH3:23])[CH3:24])[CH2:19][O:18][C:17]1[C:2]([OH:63])=[CH:3][C:4]2[C:13]3[C:8](=[CH:9][N:10]=[CH:11][CH:12]=3)[C:7](=[O:14])[N:6]([CH3:15])[C:5]=2[CH:16]=1
14
CS(C)=O
O
null
120
55
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
143,292
C[O-]
[Na+]
null
null
ord_dataset-1895fe091c3f47afa1ee96a41a250de4
1986-01-01T00:05:00
true
A mixture of sodium methoxide (7.02 g, 0.13 mole), 7,8-dimethoxy-5-formyl-2H-1-benzopyran (57 g, 0.26 mole) and 3-ethoxypropanenitrile (28.35 g, 0.286 mole) in methanol (150 mL) was heated at reflux for 4 hr, allowed to cool and diluted with water (150 mL) and ethylether (500 mL). The layers were separated and the ether portion was washed with water (3×250 mL and 1×100 mL) and dried over magnesium sulfate. The ether solution was concentrated to give 55 g (73%) of an amber oil which was used without further purification.
COCC(C#N)=Cc1cc(OC)c(OC)c2c1C=CCO2
null
CCOCCC#N
COc1cc(C=O)c2c(c1OC)OCC=C2
null
C[O-].[Na+].[CH3:4][O:5][C:6]1[CH:15]=[C:14]([CH:16]=O)[C:9]2[CH:10]=[CH:11][CH2:12][O:13][C:8]=2[C:7]=1[O:18][CH3:19].[CH2:20]([O:22][CH2:23][CH2:24][C:25]#[N:26])C>CO.O.C(OCC)C>[CH3:4][O:5][C:6]1[CH:15]=[C:14]([CH:16]=[C:24]([CH2:23][O:22][CH3:20])[C:25]#[N:26])[C:9]2[CH:10]=[CH:11][CH2:12][O:13][C:8]=2[C:7]=1[O:18][CH3:19]
null
O
CCOCC
CO
null
73.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,684,258
[Pd]
null
null
null
ord_dataset-3953983e052a4076aa7cc0880b79cb8b
2016-01-01T00:01:00
true
N-isobutyl-N-(3-methyl-5-(prop-1-en-2-yl)pyridin-2-yl)-4-((tetrahydro-2H-pyran-4-yl)methoxy)benzenesulfonamide (83 mg, 0.18 mmol) was dissolved in ethyl acetate (3 mL) and methanol (3 mL). The reaction was hydrogenated using an H-cube flow hydrogenator (settings: room temperature, 1 bar, 1 mL/min flow rate) and a 10% Pd/C CatCart as the catalyst. Two clean fractions of product were collected along with a third impure fraction, the impure fraction was then purified by mass directed autoprep (formic acid modifier). The two clean product fractions and purified third fraction were then combined and evaporated to give the title compound (61 mg). LCMS (2 min, formic) Rt 1.45 min, m/z (ES+) 461 (M+H).
Cc1cc(C(C)C)cnc1N(CC(C)C)S(=O)(=O)c1ccc(OCC2CCOCC2)cc1
null
C=C(C)c1cnc(N(CC(C)C)S(=O)(=O)c2ccc(OCC3CCOCC3)cc2)c(C)c1
null
null
[CH2:1]([N:5]([C:23]1[C:28]([CH3:29])=[CH:27][C:26]([C:30]([CH3:32])=[CH2:31])=[CH:25][N:24]=1)[S:6]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[CH:11][CH:10]=1)(=[O:8])=[O:7])[CH:2]([CH3:4])[CH3:3]>C(OCC)(=O)C.CO.[Pd]>[CH2:1]([N:5]([C:23]1[C:28]([CH3:29])=[CH:27][C:26]([CH:30]([CH3:32])[CH3:31])=[CH:25][N:24]=1)[S:6]([C:9]1[CH:10]=[CH:11][C:12]([O:15][CH2:16][CH:17]2[CH2:18][CH2:19][O:20][CH2:21][CH2:22]2)=[CH:13][CH:14]=1)(=[O:7])=[O:8])[CH:2]([CH3:4])[CH3:3]
null
CCOC(C)=O
CO
null
null
73.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,074,294
N=C=N
On1nnc2ccccc21
[N-]=C=O
null
ord_dataset-5df93261afc143c3ae919a57ff4fc1d4
2011-01-01T00:07:00
true
A 8.9 mg portion of 1-(4-fluorobenzyl)-2,3-dimethyl-1H-indole-5-carboxylic acid, 3.1 mg of N,N-dimethylpropane-1,3-diamine, 4.1 mg of 1-hydroxybenzotriazole (HOBt) and 0.0083 ml of triethylamine were dissolved in 1.0 ml of N,N-dimethylformamide, and 100 mg of PS-Carbodiimide (Argonaut Technologies, Inc., USA) was added, followed by overnight stirring at room temperature. Then, 50 mg of MP-Carbodiimide (Argonaut Technologies, Inc., USA) and 50 mg of PS-Isocyanate (Argonaut Technologies, Inc., USA) was added to the reaction liquid at room temperature, followed by stirring for 4 hours. Then, the reaction liquid was filtered. By concentrating the filtrate under a reduced pressure, 9.5 mg of N-[3-(dimethylamino)propyl]-(4-fluorobenzyl)-2,3-dimethyl-1H-indole-5-carboxamide was obtained.
Cc1c(C)n(Cc2ccc(F)cc2)c2ccc(C(=O)NCCCN(C)C)cc12
null
CN(C)CCCN
Cc1c(C)n(Cc2ccc(F)cc2)c2ccc(C(=O)O)cc12
null
[F:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([OH:18])=O)=[CH:13][CH:14]=3)[C:9]([CH3:19])=[C:8]2[CH3:20])=[CH:4][CH:3]=1.[CH3:23][N:24]([CH3:29])[CH2:25][CH2:26][CH2:27][NH2:28].ON1C2C=CC=CC=2N=N1.N=C=N.[N-]=C=O>CN(C)C=O.C(N(CC)CC)C>[CH3:23][N:24]([CH3:29])[CH2:25][CH2:26][CH2:27][NH:28][C:16]([C:12]1[CH:11]=[C:10]2[C:15](=[CH:14][CH:13]=1)[N:7]([CH2:6][C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:22][CH:21]=1)[C:8]([CH3:20])=[C:9]2[CH3:19])=[O:18]
8
CCN(CC)CC
CN(C)C=O
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
352,859
null
null
null
null
ord_dataset-127eb5fdd5b4402e92b51d0b55a5dcb5
1997-01-01T00:01:00
true
To KH (35%; (0.34 g; 0.0029 mole) in THF (8 ml) under N2 and cooled in an ice bath is added N-trityl-5-hydroxytricyclo-[3.3.1.13,7 ]decan-2-amine (1.0 g; 0.0025 mole) This forms a pale yellow solution and is stirred at room temperature for 1 hour. The reaction mixture is then cooled in ice and 4-(benzoxazol-2-yl)benzyl bromide (0.7 g; 0.0025 mole) is added all at once. The mixture is stirred for 1/2 hour with ice cooling and then 31/2 hours at room temperature then cooled in ice and MeOH is added to quench the KH. The mixture is evaporated to dryness. Purification is accomplished on HPLC eluting with a gradient system staring with 10% and ending with 20% ethyl acetate/hexane to obtain N-trityl-5-[4-(benzoxazol-2-yl)benzyloxy]tricyclo[3.3.1.13,7 ]decan-2-amine which is used directly in step F.
c1ccc(C(NC2C3CC4CC2CC(OCc2ccc(-c5nc6ccccc6o5)cc2)(C4)C3)(c2ccccc2)c2ccccc2)cc1
null
BrCc1ccc(-c2nc3ccccc3o2)cc1
OC12CC3CC(C1)C(NC(c1ccccc1)(c1ccccc1)c1ccccc1)C(C3)C2
null
[C:1]([NH:20][CH:21]1[CH:28]2[CH2:29][CH:24]3[CH2:25][C:26]([OH:31])([CH2:30][CH:22]1[CH2:23]3)[CH2:27]2)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:32]1[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[N:34]=[C:33]1[C:41]1[CH:48]=[CH:47][C:44]([CH2:45]Br)=[CH:43][CH:42]=1.CO>C1COCC1>[C:1]([NH:20][CH:21]1[CH:22]2[CH2:23][CH:24]3[CH2:25][C:26]([O:31][CH2:45][C:44]4[CH:47]=[CH:48][C:41]([C:33]5[O:32][C:36]6[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=6[N:34]=5)=[CH:42][CH:43]=4)([CH2:27][CH:28]1[CH2:29]3)[CH2:30]2)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
1
CO
C1CCOC1
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
1,743,771
O=C([O-])[O-]
[Cs+]
null
null
ord_dataset-60a3e71da3174666a50a61dcfa611a9f
2016-01-01T00:07:00
true
A mixture of methyl 5-chloro-3-hydroxy-2-methylbenzoate (1.25 g, 6.23 mmol), tert-butyl 4-((methylsulfonyl)oxy)piperidine-1-carboxylate (3.66 g, 13.08 mmol) and cesium carbonate (5.08 g, 15.58 mmol) in DMF (25 mL) was heated at 75° C. for 18 h. The reaction was allowed to cool to ambient temperature and poured into ice/water (200 mL) with stirring. The mixture was extracted with EtOAc (3×100 mL), dried over magnesium sulfate, and concentrated in vacuo. The light yellow residue was purified by flash chromatography (5-50% EtOAc/hexanes) to give tert-butyl 4-(5-chloro-3-(methoxycarbonyl)-2-methylphenoxy)piperidine-1-carboxylate (1.95 g, 5.08 mmol, 82% yield) as a solid. 1H NMR (DMSO-d6) δ 7.37 (d, J=2.0 Hz, 1H), 7.31 (d, J=2.0 Hz, 1H), 4.71 (dt, J=7.4, 3.8 Hz, 1H), 3.83 (s, 3H), 3.54-3.63 (m, 2H), 3.22-3.31 (m, 2H), 2.28 (s, 3H), 1.83-1.93 (m, 2H), 1.51-1.63 (m, 2H), 1.41 (s, 9H).
COC(=O)c1cc(Cl)cc(OC2CCN(C(=O)OC(C)(C)C)CC2)c1C
null
CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1
COC(=O)c1cc(Cl)cc(O)c1C
null
[Cl:1][C:2]1[CH:3]=[C:4]([OH:13])[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].CS(O[CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Cl:1][C:2]1[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[C:5]([CH3:12])=[C:4]([CH:3]=1)[O:13][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1
null
CN(C)C=O
null
null
75
81.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
135,435
[Na]
null
null
null
ord_dataset-3007013966624a1096d71142f31cb5a3
1985-01-01T00:10:00
true
A mixture of 9(R)-bromoacetyl-6,9,11-trihydroxy-5,7,8,9,10,12-hexahydronaphthacene-5,12-dione (1.00 g) obtained in Reference Example 4-(1), sodium octate (4.8 g) and acetone (50 ml) was stirred under reflux for 3 hours, cooled to room temperature and concentrated under reduced pressure. The residue was triturated with addition of ether (15 ml). Solid substances were filtered to give orange crystals of 9(R)-octyloxyacetyl-6,9,11-trihydroxy-5,7,8,9,10,12-hexahydronaphthacene-5,12-dione. M.P., 144°-148° C.
CCCCCCCCOCC(=O)[C@@]1(O)CCc2c(O)c3c(c(O)c2C1)C(=O)c1ccccc1C3=O
null
O=C1c2ccccc2C(=O)c2c(O)c3c(c(O)c21)CC[C@](O)(C(=O)CBr)C3
null
null
Br[CH2:2][C:3]([C@:5]1([OH:27])[CH2:22][C:21]2[C:20]([OH:23])=[C:19]3[C:10]([C:11](=[O:25])[C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=4[C:18]3=[O:24])=[C:9]([OH:26])[C:8]=2[CH2:7][CH2:6]1)=[O:4].[Na]>CC(C)=O>[CH2:3]([O:4][CH2:2][C:3]([C@:5]1([OH:27])[CH2:22][C:21]2[C:20]([OH:23])=[C:19]3[C:10]([C:11](=[O:25])[C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=4[C:18]3=[O:24])=[C:9]([OH:26])[C:8]=2[CH2:7][CH2:6]1)=[O:4])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:21][CH2:20][CH3:19]
null
CC(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
501,051
null
null
null
null
ord_dataset-d673d02cdac14dba9ff59f12845a4f37
2001-01-01T00:05:00
true
Prepared from bromine (0.21 ml, 4 mmol) and a solution of 3-methoxy-6-trifluoromethyl-2-trimethylstannylpyridine (0.7 g, 2.0 mmol) in dichloromethane (10 ml) according to the method of Description 42 to afford 4-bromo-3-methoxy-6-trifluoromethylpyridine as a yellow solid.
COc1cnc(C(F)(F)F)cc1Br
null
COc1ccc(C(F)(F)F)nc1[Sn](C)(C)C
BrBr
null
[Br:1]Br.[CH3:3][O:4][C:5]1[C:6]([Sn](C)(C)C)=[N:7][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:9][CH:10]=1>ClCCl>[Br:1][C:10]1[CH:9]=[C:8]([C:11]([F:14])([F:13])[F:12])[N:7]=[CH:6][C:5]=1[O:4][CH3:3]
null
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
null
1,144,921
null
null
null
null
ord_dataset-68715347640045adb1b09e6a04722b0e
2012-01-01T00:03:00
true
1-[(2-Amino-4-chloro-1H-imidazo[4,5-c]quinolin-1-yl)methyl]cyclobutanol (1.14 g, 3.77 mmol) and ammonia (15 mL of a 7 N solution in methanol) were added to a pressure vessel, which was sealed and heated at 150° C. for five days. Additional ammonia in methanol (50 mL) was added after two days. When the reaction was complete, the volatiles were removed under reduced pressure, and the residue was triturated sequentially with methanol and saturated aqueous sodium bicarbonate and isolated by filtration. The resulting yellow solid was purified by automated flash chromatography on silica gel (40+M cartridge, eluting with 0% to 75% CMA in chloroform) followed by recrystallization from methanol. The crystals were dried overnight in a vacuum oven at 90° C. to provide 0.240 g of 1-[(2,4-diamino-1H-imidazo[4,5-c]quinolin-1-yl)methyl]cyclobutanol as pale yellow crystals, mp 295° C. (decomposition).
Nc1nc2ccccc2c2c1nc(N)n2CC1(O)CCC1
null
N
Nc1nc2c(Cl)nc3ccccc3c2n1CC1(O)CCC1
null
[NH2:1][C:2]1[N:3]([CH2:16][C:17]2([OH:21])[CH2:20][CH2:19][CH2:18]2)[C:4]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N:7]=[C:6](Cl)[C:5]=2[N:15]=1.[NH3:22]>CO>[NH2:1][C:2]1[N:3]([CH2:16][C:17]2([OH:21])[CH2:20][CH2:19][CH2:18]2)[C:4]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N:7]=[C:6]([NH2:22])[C:5]=2[N:15]=1
null
CO
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
424,247
[BH3-]C#N
[Na+]
null
null
ord_dataset-1a231de00bfe4443b547e1f03885ed41
1999-01-01T00:01:00
true
4-Amino-N-((1-(5-benzylaminopentyl)piperidin-4-yl)methyl)-5-chloro-2-methoxybenzamide (2.0 g) as starting compound, propionaldehyde (0.13 ml) and sodium cyanoborohydride (0.35 g) were reacted and treated in the same manner as in Example 136 to give 1.05 g of 4-amino-5-chloro-2-methoxy-N-((1-(5-(N-n-propyl-N-benzylamino)pentyl)piperidin-4-yl)methyl)-benzamide.
CCCN(CCCCCN1CCC(CNC(=O)c2cc(Cl)c(N)cc2OC)CC1)Cc1ccccc1
null
COc1cc(N)c(Cl)cc1C(=O)NCC1CCN(CCCCCNCc2ccccc2)CC1
CCC=O
null
[NH2:1][C:2]1[C:30]([Cl:31])=[CH:29][C:5]([C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][NH:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:12][CH2:11]2)=[O:7])=[C:4]([O:32][CH3:33])[CH:3]=1.[CH:34](=O)[CH2:35][CH3:36].C([BH3-])#N.[Na+]>>[NH2:1][C:2]1[C:30]([Cl:31])=[CH:29][C:5]([C:6]([NH:8][CH2:9][CH:10]2[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]([CH2:34][CH2:35][CH3:36])[CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:14][CH2:15]2)=[O:7])=[C:4]([O:32][CH3:33])[CH:3]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
694,855
[Mg+]
null
null
null
ord_dataset-a7baa616c65d42559e25ca0ba61e0744
2006-01-01T00:01:00
true
To a solution of 4-(pyridin-3-yloxy)benzoic acid (11.2 g, 52.0 mmol) in tetrahydrofuran (160 ml) was added N,N′-carbonyldiimidazole (9.28 g, 57.3 mmol), and the mixture was heated under reflux for 3 hrs. After cooling the reaction solution to room temperature, monobenzyl malonate magnesium salt (11.7 g, 28.6 mmol) was added, and the mixture was heated under reflux for 2 hrs. The reaction solution was concentrated and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give the objective substance (14.1 g, 78%).
O=C(CC(=O)c1ccc(Oc2cccnc2)cc1)OCc1ccccc1
null
O=C(O)c1ccc(Oc2cccnc2)cc1
O=C([O-])CC(=O)OCc1ccccc1
null
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)[CH:2]=1.[Mg+].[C:18]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=[O:23])[CH2:19]C([O-])=O>O1CCCC1>[O:14]=[C:12]([C:11]1[CH:10]=[CH:9][C:8]([O:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[CH:16][CH:15]=1)[CH2:19][C:18]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23]
null
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
1,201,725
null
null
null
null
ord_dataset-fb72428f30234761b4216139dc228d0c
2012-01-01T00:09:00
true
1-{5-[1-(4-Fluoro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-yl}-piperidine-4-carboxylic acid was prepared from 1-(4-Fluoro-2-trifluoromethyl-benzyl)-1H-indazole-5-carbaldehyde and 1-(4-Oxo-4,5-dihydro-thiazol-2-yl)piperidine-4-carboxylic acid following General Procedure E.
O=C1N=C(N2CCC(C(=O)O)CC2)SC1=Cc1ccc2c(cnn2Cc2ccc(F)cc2C(F)(F)F)c1
null
O=Cc1ccc2c(cnn2Cc2ccc(F)cc2C(F)(F)F)c1
O=C1CSC(N2CCC(C(=O)O)CC2)=N1
null
[F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=O)=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:20]([F:23])([F:22])[F:21])[CH:3]=1.[O:24]=[C:25]1[CH2:29][S:28][C:27]([N:30]2[CH2:35][CH2:34][CH:33]([C:36]([OH:38])=[O:37])[CH2:32][CH2:31]2)=[N:26]1>>[F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:29]4[S:28][C:27]([N:30]5[CH2:31][CH2:32][CH:33]([C:36]([OH:38])=[O:37])[CH2:34][CH2:35]5)=[N:26][C:25]4=[O:24])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:20]([F:21])([F:23])[F:22])[CH:3]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
323,674
[NH2-]
[Na+]
null
null
ord_dataset-24ad29d930104afea313b6c3bd11099e
1996-01-01T00:01:00
true
32.1 g (0.25 mol) of o-chlorophenol were slowly added dropwise under nitrogen to a mixture of 20.5 g (0.5 mol) of 95% by weight pure crystalline sodium amide and 750 ml of diethylamine. The reaction mixture was refluxed under nitrogen for 72 h with stirring. The workup comprised hydrolysis with 100 ml of saturated aqueous ammonium chloride solution, distillative removal of excess diethylamine, neutralization with dilute hydrochloric acid up to a pH of 7.5, extraction of the residue with a total of 600 ml of methylene chloride, drying over sodium sulfate and concentrating of the organic phase. Thereafter the crude oil thus obtained (46.3 g) was distilled, which yielded 31.5 g (76%) of 3-diethylaminophenol (purity>96% (GC)).
CCN(CC)c1cccc(O)c1
null
CCNCC
Oc1ccccc1Cl
null
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].[NH2-].[Na+].[CH2:11]([NH:13][CH2:14][CH3:15])[CH3:12]>>[CH2:11]([N:13]([CH2:14][CH3:15])[C:7]1[CH:2]=[C:3]([OH:8])[CH:4]=[CH:5][CH:6]=1)[CH3:12]
null
null
null
null
null
76
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,739,558
null
null
null
null
ord_dataset-eacfee6d16d8455a93348409f1b37be4
2016-01-01T00:06:00
true
Compound 51 was prepared from pivalamide and 4-(diethylamino)benzaldehyde using method 1. Yield: 77%. 1H NMR (400 MHz, DMSO) δ 7.70 (d, J=8.8 Hz, 2H), 7.03 (d, J=8.8 Hz, 2H), 6.62 (d, J=8.8 Hz, 2H), 6.52 (t, J=8.4 Hz, 1H), 3.30-3.33 (m, 4H), 1.12 (s, 18H), 1.05-1.08 (m, 6H). LC-MS (ESI): m/z 262.2 (M+H)+. HRMS (ESI) for C21H36N3O2 (MH+): calcd, 362.2802. found 362.2795.
CCN(CC)c1ccc(C(NC(=O)C(C)(C)C)NC(=O)C(C)(C)C)cc1
null
CC(C)(C)C(N)=O
CCN(CC)c1ccc(C=O)cc1
null
[C:1]([NH2:7])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[CH2:8]([N:10]([CH2:19][CH3:20])[C:11]1[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=1)[CH3:9]>>[CH2:8]([N:10]([CH2:19][CH3:20])[C:11]1[CH:18]=[CH:17][C:14]([CH:15]([NH:7][C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])[NH:7][C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])=[CH:13][CH:12]=1)[CH3:9]
null
null
null
null
null
77
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
46,645
CN
null
null
null
ord_dataset-6d529f04a1724b5d85dcc290cf4c38bb
1978-01-01T00:10:00
true
In a similar manner N,N'-bis-[2-((5-methyl-4-imidazolyl)-methylthio)ethyl]-N"-butylguanidine may be prepared using butylamine in ethanol in place of ethanolic methylamine.
CN=C(NCCSCc1nc[nH]c1C)NCCSCc1nc[nH]c1C
null
CCCCN=C(NCCSCc1nc[nH]c1C)NCCSCc1nc[nH]c1C
null
null
[CH3:1][C:2]1[NH:6][CH:5]=[N:4][C:3]=1[CH2:7][S:8][CH2:9][CH2:10][NH:11][C:12]([NH:18][CH2:19][CH2:20][S:21][CH2:22][C:23]1[N:24]=[CH:25][NH:26][C:27]=1[CH3:28])=[N:13][CH2:14]CCC.C(N)CCC.CN>C(O)C>[CH3:28][C:27]1[NH:26][CH:25]=[N:24][C:23]=1[CH2:22][S:21][CH2:20][CH2:19][NH:18][C:12]([NH:11][CH2:10][CH2:9][S:8][CH2:7][C:3]1[N:4]=[CH:5][NH:6][C:2]=1[CH3:1])=[N:13][CH3:14]
null
CCCCN
CCO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
477,014
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-21c1b1c06c7e4e09a38b5b1c71a32e52
2000-01-01T00:10:00
true
To a solution of 2-methoxymethoxy-4-methoxyphenyl boronic acid (2.89 g, 13.65 mmol) in MeOH (8-10 ml) and 6-benzyloxymethyl-5-iodo-4-propoxy-pyrimidine (5 g, 13 mmol) in toluene (75 ml) was added an aqueous solution of 2 M sodium carbonate (14 ml) followed by Tetrakis(triphenylphosphine)palladium (0) (1.25 g, 1.08 mmol). The reaction was allowed to stir at 90-95° for 18 h. The mixture was cooled to room temperature then diluted with ethyl acetate, washed with water, sat'd NH4Cl, 5% NaHCO3 solution, brine and dried (MgSO4). After removing the solvent, flash chromatography of the residue (silica gel, 1:1 t-butyl methyl ether/hexane) provided the title compound as a solid (3.41 g, 62%).
CCCOc1ncnc(COCc2ccccc2)c1-c1ccc(OC)cc1OCOC
null
COCOc1cc(OC)ccc1B(O)O
CCCOc1ncnc(COCc2ccccc2)c1I
null
[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:6]=1B(O)O.[CH2:16]([O:23][CH2:24][C:25]1[N:30]=[CH:29][N:28]=[C:27]([O:31][CH2:32][CH2:33][CH3:34])[C:26]=1I)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(=O)([O-])[O-].[Na+].[Na+]>CO.C1(C)C=CC=CC=1.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>[CH2:16]([O:23][CH2:24][C:25]1[N:30]=[CH:29][N:28]=[C:27]([O:31][CH2:32][CH2:33][CH3:34])[C:26]=1[C:6]1[CH:7]=[CH:8][C:9]([O:11][CH3:12])=[CH:10][C:5]=1[O:4][CH2:3][O:2][CH3:1])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
18
Cc1ccccc1
CCOC(C)=O
CO
25
61.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
234,559
Cl
null
null
null
ord_dataset-45d20d09e4d64f45bdd419044025b4d3
1991-01-01T00:09:00
true
6.3 g of E-2-formylamino-3-methyl-5-diethylphosphono-3-pentenoic acid ethylester are heated for 30 hours at 100°-100° under nitrogen in 400 ml of 4.35N hydrochloric acid. Working up as in Example 11 yields E-2-amino-3-methyl-5-phosphono-3-pentenoic acid in the form of a white powder, m.p. 168°, 1H-NMR (D2O): 1.50 (d, 3H, CH3); 2.4 (m, 2H, CH2); 4.30 (s, 1H, C(2)--H); 5.60 (m, 1H, C(4)--H).
C/C(=C\CP(=O)(O)O)C(N)C(=O)O
null
CCOC(=O)C(NC=O)/C(C)=C/CP(=O)(OCC)OCC
null
null
C([O:3][C:4](=[O:21])[CH:5]([NH:18]C=O)/[C:6](/[CH3:17])=[CH:7]/[CH2:8][P:9]([O:14]CC)([O:11]CC)=[O:10])C>Cl>[NH2:18][CH:5](/[C:6](/[CH3:17])=[CH:7]/[CH2:8][P:9]([OH:14])([OH:11])=[O:10])[C:4]([OH:21])=[O:3]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
787,522
CC(=O)O[BH-](OC(C)=O)OC(C)=O
[Na+]
null
null
ord_dataset-4ad5db8537994579bef51f16dd8bf0bd
2007-01-01T00:08:00
true
A solution of 4-(3-phenylpyrazolo[1,5-a]pyrimidin-6-yl)benzaldehyde (1-5, 75 mg, 0.25 mmol), benzylamine (0.056 mL, 0.50 mmol), acetic acid (14 TL, 0.25 mmol), and sodium triacetoxyborohydride(106 mg, 0.50 mmol) in 1,2-dichloro-ethane (6 mL) was stirred under ambient conditions overnight. The residue was partitioned between sat. NaHCO3 solution (4 mL) and ethyl acetate (3×4 mL). The organic layer was washed with brine and dried over MgSO4 and concentrated. The residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present) to provide 1-phenyl-N-[4-(3-phenylpyrazolo[1,5-a]pyrimidin-6-yl)benzyl]methanamine (1-6) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ9.21 (d, 1H, J=2.4 Hz), 8.96 (d, 1H, J=2.4 Hz), 8.61 (s, 1H), 8.12 (br d, 2H, J=7.8 Hz), 7.91 (d, 2H, J=8.2 Hz), 7.67 (d, 2H, J=7.8 Hz), 7.49 (m, 5H), 7.44 (br t, 2H, J=7.8 Hz), 7.27 (t, 1H, J=7.5 Hz), 4.34 (s, 2H), 4.29 (s, 2H).
c1ccc(CNCc2ccc(-c3cnc4c(-c5ccccc5)cnn4c3)cc2)cc1
null
NCc1ccccc1
O=Cc1ccc(-c2cnc3c(-c4ccccc4)cnn3c2)cc1
null
[C:1]1([C:7]2[CH:8]=[N:9][N:10]3[CH:15]=[C:14]([C:16]4[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][CH:17]=4)[CH:13]=[N:12][C:11]=23)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:24]([NH2:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:25]1([CH2:24][NH:31][CH2:20][C:19]2[CH:22]=[CH:23][C:16]([C:14]3[CH:13]=[N:12][C:11]4[N:10]([N:9]=[CH:8][C:7]=4[C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH:15]=3)=[CH:17][CH:18]=2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
null
ClCCCl
CC(=O)O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,593,551
null
null
null
null
ord_dataset-e8c6a25568b64529b960953990e6921f
2015-01-01T00:06:00
true
The title compound was prepared by a procedure similar to that described for E9 starting from (3-fluoro-4-((2-(trifluoromethyl)pyrimidin-5-yl)oxy)phenyl)methanol and tert-buty-7-chloro-2,2-dimethyl-5-oxo-2,3-dihydroimidazo[1,2-c]pyrimidine-1(5H)-carboxylate.
CC1(C)Cn2c(cc(OCc3ccc(Oc4cnc(C(F)(F)F)nc4)c(F)c3)nc2=O)N1
null
CC(C)(C)OC(=O)N1c2cc(Cl)nc(=O)n2CC1(C)C
OCc1ccc(Oc2cnc(C(F)(F)F)nc2)c(F)c1
null
[F:1][C:2]1[CH:3]=[C:4]([CH2:19][OH:20])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:10]=[N:11][C:12]([C:15]([F:18])([F:17])[F:16])=[N:13][CH:14]=1.C(OC([N:28]1[C:36]2[N:31]([C:32](=[O:38])[N:33]=[C:34](Cl)[CH:35]=2)[CH2:30][C:29]1([CH3:40])[CH3:39])=O)(C)(C)C>>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[N:13][C:12]([C:15]([F:17])([F:18])[F:16])=[N:11][CH:10]=1)[CH2:19][O:20][C:34]1[CH:35]=[C:36]2[NH:28][C:29]([CH3:40])([CH3:39])[CH2:30][N:31]2[C:32](=[O:38])[N:33]=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
59,816
null
null
null
null
ord_dataset-09e9a37ee5794dc28c0ad7bf7a442c18
1979-01-01T00:11:00
true
2-(2,2,2-Trifluoroethoxy)-5-aminopyridine (0.5 gram) and 2,6-dichlorobenzoyl isocyanate (0.5 gram) were mixed in ethyl acetate, and the reaction mixture stirred overnight (about 18 hours) at room temperature. Solvent was removed by evaporation and the product residue crystallized from ethyl acetate-hexanes, yield 0.6 gram, m.p., 146°-148° C.
O=C(NC(=O)c1c(Cl)cccc1Cl)Nc1ccc(OCC(F)(F)F)nc1
null
Nc1ccc(OCC(F)(F)F)nc1
O=C=NC(=O)c1c(Cl)cccc1Cl
null
[F:1][C:2]([F:13])([F:12])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[CH:7][N:6]=1.[Cl:14][C:15]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:16]=1[C:17]([N:19]=[C:20]=[O:21])=[O:18]>C(OCC)(=O)C>[Cl:14][C:15]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:16]=1[C:17]([NH:19][C:20]([NH:11][C:8]1[CH:7]=[N:6][C:5]([O:4][CH2:3][C:2]([F:1])([F:12])[F:13])=[CH:10][CH:9]=1)=[O:21])=[O:18]
18
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
476,791
O=S(=O)([O-])[O-]
[Na+]
[OH-]
null
ord_dataset-d56f0a7ec215495c92e641d9fa932d28
2000-01-01T00:09:00
true
Starting from 2,6-dichlorobenzaldehyde 75 g (0.43 mol) of 2,6-dichlorobenzaldehyde were dissolved in 400 ml of toluene and then 155 g (0.24 mol) of 25% strength hydroxylammonium sulfate solution were added. At 75° C., 38 g of 50% strength NaOH were added dropwise. After stirring for half an hour, the phases were separated at 75° C., and the organic phase was washed with water and then cooled. At 25° C., 276 g (0.46 mol) of 12.5% strength sodium hypochlorite solution were added dropwise over 4-6 h while simultaneously passing in ethylene. After addition of the hypochlorite solution was complete, the mixture was stirred for 1 h, the phases were separated, the organic phase was washed with water, and the solvent was distilled off under reduced pressure. 82 g (89% of theory) of the required product were obtained with a purity (by GC) of 96%.
Clc1cccc(Cl)c1C1=NOCC1
null
Cc1ccccc1
O=Cc1c(Cl)cccc1Cl
[NH3+]O
[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[CH:4]=O.S([O-])([O-])(=O)=O.[OH:16][NH3+:17].O[NH3+].[OH-].[Na+].[C:22]1([CH3:28])C=CC=CC=1>>[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[C:4]1[CH2:28][CH2:22][O:16][N:17]=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
758,978
null
null
null
null
ord_dataset-2e58cb8db2bf482bbea23283b7e04488
2007-01-01T00:03:00
true
To a stirred solution of 2-aminophenol (2.18 g, 20 mmol) in acetone (20 mL) a solution of 3-chloropropionyl chloride (1.28 g, 0.87 mL, 10 mmol) in acetone (20 mL) was added dropwise. After the addition was completed, the reaction mixture was stirred at room temperature for 0.5 h and then diluted with water (50 mL). Acetone was removed in vacuo, the precipitate formed was collected by filtration, washed with water, and dried to give the subtitle compound (1.53 g, 77%).
O=C(CCCl)Nc1ccccc1O
null
Nc1ccccc1O
O=C(Cl)CCCl
null
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].[Cl:9][CH2:10][CH2:11][C:12](Cl)=[O:13]>CC(C)=O.O>[Cl:9][CH2:10][CH2:11][C:12]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8])=[O:13]
0.5
O
CC(C)=O
null
25
76.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
801,228
[H-]
[Na+]
null
null
ord_dataset-56a22bc0c3b14f87b9aa3f2fc6488ee7
2007-01-01T00:12:00
true
A solution of diethyl hydroxymethylphosphonate (1 mmole) in toluene was treated with sodium hydride (1.1 mmole) at 0° C., and after 15 min 2-bromomethyl-4,6-dimethylpyridine (1 mmole) was added. After 3 h the reaction mixture was subjected to extraction and chromatography to give 2-diethylphosphonomethyl-4,6-dimethylpyridine.
CCOP(=O)(Cc1cc(C)cc(C)n1)OCC
null
Cc1cc(C)nc(CBr)c1
CCOP(=O)(CO)OCC
null
O[CH2:2][P:3](=[O:10])([O:7][CH2:8][CH3:9])[O:4][CH2:5][CH3:6].[H-].[Na+].Br[CH2:14][C:15]1[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17](C)[N:16]=1>C1(C)C=CC=CC=1>[CH2:5]([O:4][P:3]([CH2:2][C:17]1[CH:18]=[C:19]([CH3:21])[CH:20]=[C:15]([CH3:14])[N:16]=1)([O:7][CH2:8][CH3:9])=[O:10])[CH3:6]
null
Cc1ccccc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,425,069
Cl
O=C([O-])O
[Na+]
null
ord_dataset-5e6956e6e8c24a168866a253f4a66c6c
2014-01-01T00:05:00
true
To a round bottom flask was added 3-amino-adamantane-1-carboxylic acid methyl ester hydrochloride (20.0 g, 81.4 mmol) and methylene chloride (500 mL) and the solution was cooled at 0° C. To this solution was then added triethylamine (57 mL, 0.41 mol) followed by picolinoyl chloride hydrochloride (15.2 g 85.4 mmol; TCI America, Wellesley Hills, Mass., USA) and the reaction was stirred at 0° C. for 30 minutes, then at room temperature for 6 hours. To the reaction was added saturated aqueous sodium bicarbonate (500 mL) and the biphasic mixture was stirred vigorously for a few minutes, then transferred to a 2-L separatory funnel. The mixture was extracted, the layers separated and the aqueous layer was extracted again with methylene chloride (2×200 mL). The combined organic layers were washed with brine (300 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 24.8 g (97%) of the title compound, 3-[(pyridine-2-carbonyl)-amino]-adamantane-1-carboxylic acid methyl ester, as a pale brown solid. 1H NMR (400 MHz, CDCl3) δ 8.54-8.49 (m, 1H), 8.16 (dt, J=7.8, 1.0 Hz, 1H), 7.96 (br s, 1H), 7.83 (td, J=7.8, 1.8 Hz, 1H), 7.40 (ddd, J=7.6, 4.8, 1.3 Hz, 1H), 3.66 (s, 3H), 2.34-2.30 (m, 2H), 2.29-2.23 (m, 2H), 2.17-2.13 (m, 4H), 1.97-1.80 (m, 4H), 1.78-1.62 (m, 2H). ESI-MS m/z: 315.0 (M+H)+.
COC(=O)C12CC3CC(CC(NC(=O)c4ccccn4)(C3)C1)C2
null
O=C(Cl)c1ccccn1
COC(=O)C12CC3CC(CC(N)(C3)C1)C2
null
Cl.[CH3:2][O:3][C:4]([C:6]12[CH2:15][CH:10]3[CH2:11][CH:12]([CH2:14][C:8]([NH2:16])([CH2:9]3)[CH2:7]1)[CH2:13]2)=[O:5].C(N(CC)CC)C.Cl.[N:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31](Cl)=[O:32].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH3:2][O:3][C:4]([C:6]12[CH2:15][CH:10]3[CH2:11][CH:12]([CH2:14][C:8]([NH:16][C:31]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][N:25]=4)=[O:32])([CH2:9]3)[CH2:7]1)[CH2:13]2)=[O:5]
0.5
CCN(CC)CC
ClCCl
null
0
null
96.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null