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
1,098,520
Cl
null
null
null
ord_dataset-af85e6f81c2d49f08086afd6d9e6959c
2011-01-01T00:10:00
true
A mixture of 4-oxo-cyclohexanecarboxylic acid (4.05 g, 28.5 mmol) and phenylhydrazine hydrochloride (4.12 g, 28.5 mmol) in EtOH (200 ml) is stirred at reflux for 3 h. Then, the solvent is evaporated and the residue is dissolved in boiling toluene. Precipitating ammonium chloride is filtered off and the clear filtrate is cooled to rt. The resulting precipitate is filtered and tried under high vacuum to give pure subtitle compound as a white solid (5.16 g) in 84% yield. tR (LC-3) 2.21 min; ESI-MS (positive ion): m/z 216.30 [M+H]+(calcd 215.09 for C13H13NO2). 1H-NMR (CDCl3): 2.01 (m, 1H); 2.28 (m, 1H); 2.83 (m, 4H); 3.04 (dd, J=14.8 Hz, 4.7 Hz, 1H); 7.02 (m, 2H); 7.19 (d, J=7.2 Hz, 1H); 7.38 (d, J=7.0 Hz, 1H); 7.63 (s br, 1H).
O=C(O)C1CCc2[nH]c3ccccc3c2C1
null
O=C1CCC(C(=O)O)CC1
NNc1ccccc1
null
O=[C:2]1[CH2:7][CH2:6][CH:5]([C:8]([OH:10])=[O:9])[CH2:4][CH2:3]1.Cl.[C:12]1([NH:18]N)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>CCO>[CH2:7]1[C:2]2[NH:18][C:12]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:3]=2[CH2:4][CH:5]([C:8]([OH:10])=[O:9])[CH2:6]1
null
CCO
null
null
25
84.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
870,001
O=C1CCc2cccc(Nc3ncc(-c4ccc(C(F)(F)F)cc4)o3)c2C1
null
null
null
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
2009-01-01T00:03:00
true
The title compound was prepared using the procedure as described in Example 2, substituting the product of Example 8C for the product of Example 1I. 1H NMR (DMSO-d6) 69.17 (s, 1H), 7.43-7.57 (m, 6H), 7.10 (t, 1H, J=7.3 Hz), 6.81 (d, 1H, J=6.8 Hz), 4.80 (d, 1H, J=3.9 Hz), 3.90 (m, 1H), 2.68-2.96 (m, 4H), 1.82 (m, 1H), 1.60 (m, 1H); MS (ESI+) m/z 385/387 (M+H, 79Br/81Br).
OC1CCc2cccc(Nc3ncc(-c4ccc(Br)cc4)o3)c2C1
null
O=C1CCc2cccc(Nc3ncc(-c4ccc(Br)cc4)o3)c2C1
null
null
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([NH:13][C:14]3[CH:15]=[CH:16][CH:17]=[C:18]4[C:23]=3[CH2:22][C:21](=[O:24])[CH2:20][CH2:19]4)=[N:10][CH:9]=2)=[CH:4][CH:3]=1.FC(F)(F)C1C=CC(C2OC(NC3C=CC=C4C=3CC(=O)CC4)=NC=2)=CC=1>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([NH:13][C:14]3[CH:15]=[CH:16][CH:17]=[C:18]4[C:23]=3[CH2:22][CH:21]([OH:24])[CH2:20][CH2:19]4)=[N:10][CH:9]=2)=[CH:4][CH:3]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
910,577
Cl
[Li+]
[OH-]
null
ord_dataset-c663259b80f947e2a8923796fb0e9a6b
2009-01-01T00:10:00
true
To a solution of methyl [1-((3S)-3-isopropyl-3-{[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopentyl)piperidin-4-yl]acetate (470 mgs, 0.92 mmol) in methanol (5 ml) was added 2N Lithium Hydroxide solution (1.8 ml, 3.7 mmol), the reaction was then stirred overnight at room temperature. The reaction was neutralized to pH=5 using 3N HCl. The crude was purified on reverse phase HPLC using 5%-100% ACN/H2O to yield [1-((3S)-3-{[3-(1,1-difluoroethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}-3-isopropylcyclopentyl)piperidin-4-yl]acetic acid (320 mgs, 91%), LC-MS 482 (M++1).
CC(C)[C@]1(C(=O)N2CCc3ncc(C(C)(F)F)cc3C2)CCC(N2CCC(CC(=O)O)CC2)C1
null
COC(=O)CC1CCN(C2CC[C@@](C(=O)N3CCc4ncc(C(F)(F)F)cc4C3)(C(C)C)C2)CC1
CO
null
[CH:1]([C@:4]1([C:20]([N:22]2[CH2:31][CH2:30][C:29]3[N:28]=[CH:27][C:26]([C:32]([F:35])(F)[F:33])=[CH:25][C:24]=3[CH2:23]2)=[O:21])[CH2:8][CH2:7][CH:6]([N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][C:16]([O:18]C)=[O:17])[CH2:11][CH2:10]2)[CH2:5]1)([CH3:3])[CH3:2].[OH-].[Li+].Cl.[CH3:39]O>>[F:35][C:32]([C:26]1[CH:27]=[N:28][C:29]2[CH2:30][CH2:31][N:22]([C:20]([C@@:4]3([CH:1]([CH3:2])[CH3:3])[CH2:8][CH2:7][CH:6]([N:9]4[CH2:10][CH2:11][CH:12]([CH2:15][C:16]([OH:18])=[O:17])[CH2:13][CH2:14]4)[CH2:5]3)=[O:21])[CH2:23][C:24]=2[CH:25]=1)([F:33])[CH3:39]
8
null
null
null
25
null
91
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,516,828
CS(N)(=O)=O
null
null
null
ord_dataset-8c74302143c04eb9983e4b3a7ead2d72
2014-01-01T00:12:00
true
Compound 10h was synthesized by a procedure similar to that described for (R)-10a using (Z)-tert-butyl(1-(naphthalen-1-yl)prop-1-enyloxy)dimethylsilane, (9h, 4.58 g, 0.015 mol), AD-mix-β (21.4 g), and CH3SO2NH2 (1.5 g, 0.0158 mol) in tert-butyl alcohol-water (60 mL:60 mL). The reaction was quenched with sodium sulfite (15.3 g). After purification by column chromatography on silica gel, 1.15 g (38%) of the title product was isolated plus 2.1 g of starting olefin was recovered, raising the effective yield to 70%: [α]20D +140.2° (c 3.2, CHCl3); 1H NMR (CDCl3) δ 8.51-8.46 (m, 1H), 8.04 (d, 1H, J=8.3 Hz), 7.93-7.87 (m, 1H), 7.80-7.75 (m, 1H), 7.66-7.48 (m, 3H), 5.30-5.17 (m, 1H), 3.96 (d, 111, J=5.8 Hz), 1.36 (d, 3H, J=7.1 Hz); 13C NMR (CDCl3) δ 205.7, 134.1, 133.5, 132.5, 130.7, 128.7, 128.4, 127.7, 126.9, 125.5, 124.4, 71.2, 21.3; LCMS (ESI) m/z 201.2 [(M+H)+, M=C13H12O2].
C[C@@H](O)C(=O)c1cccc2ccccc12
null
C/C=C(\O[Si](C)(C)C(C)(C)C)c1cccc2ccccc12
CC[C@H]1CN2CC[C@H]1C[C@@H]2[C@@H](Oc1nnc(O[C@@H](c2ccnc3ccc(OC)cc23)[C@H]2C[C@@H]3CCN2C[C@@H]3CC)c2ccccc12)c1ccnc2ccc(OC)cc12
null
C([Si]([O:8]/[C:9](/[C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][CH:13]=1)=[CH:10]\[CH3:11])(C)C)(C)(C)C.CC[C@@H]1[C@@H]2C[C@H]([C@@H](OC3C4C(=CC=CC=4)C(O[C@@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C([O:43]C)C=C4)N(CC2)C1.CS(N)(=O)=O>C(O)(C)(C)C.O>[OH:43][C@H:10]([CH3:11])[C:9]([C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][CH:13]=1)=[O:8]
null
CC(C)(C)O
O
null
null
null
38.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,271,236
null
null
null
null
ord_dataset-d3580a12b15e46cc91aa73f4f1a4a8cc
2013-01-01T00:03:00
true
The title compound, MS: m/e=374.1 (M+H+), was prepared in accordance with the general method of example 1 from 2,6-dichloroquinoline, 2-methoxybenzylamine and (1-methyl-1H-imidazol-5-yl)methylamine.
COc1ccccc1CNc1ccc2cc(NCc3cncn3C)ccc2n1
null
Clc1ccc2nc(Cl)ccc2c1
Cn1cncc1CN
COc1ccccc1CN
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7](Cl)[CH:8]=2)[N:3]=1.[CH3:13][O:14][C:15]1[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=1[CH2:17][NH2:18].[CH3:23][N:24]1[C:28]([CH2:29][NH2:30])=[CH:27][N:26]=[CH:25]1>>[CH3:13][O:14][C:15]1[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=1[CH2:17][NH:18][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:30][CH2:29][C:28]3[N:24]([CH3:23])[CH:25]=[N:26][CH:27]=3)[CH:8]=2)[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
849,092
null
null
null
null
ord_dataset-171b840ae6e84e45bab43b987d09f5c7
2008-01-01T00:11:00
true
A mixture of 2-amino-4-(2-chlorophenyl)-thiophene-3-carboxylic acid ethyl ester (2 mmol, Example 8, Part B) and phthalic anhydride (2.2 mmol) in glacial acetic acid (20 mL) is heated at reflux overnight. After cooling to room temperature, the acetic acid is removed in vacuo and the residue triturated with petroleum ether. The crude product is collected by filtration, suspended in acetyl chloride (5 mL), and heated to reflux for one hour. After removing the solvent in vacuo, the residue is dissolved in ethyl acetate (30 mL), washed sequentially with 5% aqueous NaHCO3 (10 mL), water (10 mL), brine (10 mL), dried (Na2SO4), filtered, and concentrated in vacuo. Recrystallization from petroleum ether affords the desired product.
CCOC(=O)c1c(-c2ccccc2Cl)csc1N1C(=O)c2ccccc2C1=O
null
O=C1OC(=O)c2ccccc21
CCOC(=O)c1c(-c2ccccc2Cl)csc1N
null
[CH2:1]([O:3][C:4]([C:6]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])=[CH:9][S:8][C:7]=1[NH2:18])=[O:5])[CH3:2].[C:19]1(=O)[O:24][C:22](=[O:23])[C:21]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:20]12>C(O)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])=[CH:9][S:8][C:7]=1[N:18]1[C:22](=[O:23])[C:21]2[C:20](=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:19]1=[O:24])=[O:5])[CH3:2]
null
CC(=O)O
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,607,674
[Li+]
[OH-]
null
null
ord_dataset-9cecb3a8d3b9494191b28dcefea66af2
2015-01-01T00:07:00
true
Add lithium hydroxide (0.10 g, 4.18 mmol) to a suspension of 3-[(4-cyano-phenylcarbamoyl)-methoxy]-benzoic acid methyl ester (0.50 g, 1.61 mmol) in a 1:1:1 mixture of water: MeOH: tetrahydrofuran. Stir the mixture at room temperature for 36 h then dilute with water and wash with EtOAc. Adjust the pH of the aqueous phase by the addition of a 1 N solution of hydrochloric acid. Extract the mixture with EtOAc and dry the combined organic phase over anhydrous sodium sulfate. Concentrate under reduced pressure to provide 0.290 g of 3-[(4-cyano-phenylcarbamoyl)-methoxy]-benzoic acid as a solid.
N#Cc1ccc(NC(=O)COc2cccc(C(=O)O)c2)cc1
null
COC(=O)c1cccc(OCC(=O)Nc2ccc(C#N)cc2)c1
null
null
[OH-].[Li+].C[O:4][C:5](=[O:25])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH2:13][C:14](=[O:24])[NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=2)[CH:7]=1.CO.O1CCCC1>O>[C:22]([C:19]1[CH:18]=[CH:17][C:16]([NH:15][C:14]([CH2:13][O:12][C:8]2[CH:7]=[C:6]([CH:11]=[CH:10][CH:9]=2)[C:5]([OH:25])=[O:4])=[O:24])=[CH:21][CH:20]=1)#[N:23]
36
O
C1CCOC1
CO
25
null
60.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
866,651
[I-]
[Na+]
null
null
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
2009-01-01T00:03:00
true
Sodium iodide (1.4 g, 9.3 mmol) was added to a solution of chloromethyl isopropyl carbonate (750 mg, 4.8 mmol) in acetone (5 mL). The resulting mixture was stirred at room temperature for 2.5 h, followed by addition of 2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-amine (500 mg, 1.6 mmol). The reaction mixture was then stirred at room temperature for 7 d. The reaction mixture was concentrated under reduced pressure to provide isopropyl 3-(2-(3-(2,6-dichlorophenyl)isoxazol-5-yl)pyridin-4-ylamino)propanoate, which was carried forward without further purification. 1H NMR (CDCl3): 8.56 (d, 1H), 7.96 (s, 1H), 7.62 (m, 1H), 7.42-7.30 (m, 4H), 7.01 (s, 1H), 6.26 (d, 2H), 5.02 (m, 1H), 1.31 ppm (d, 6H).
CC(C)OC(=O)CCNc1ccnc(-c2cc(-c3c(Cl)cccc3Cl)no2)c1
null
CC(C)=O
CC(C)OC(=O)OCCl
Nc1ccnc(-c2cc(-c3c(Cl)cccc3Cl)no2)c1
[I-].[Na+].[C:3](=[O:11])([O:7][CH:8]([CH3:10])[CH3:9])OCCl.[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=1[C:20]1[CH:24]=[C:23]([C:25]2[CH:30]=[C:29]([NH2:31])[CH:28]=[CH:27][N:26]=2)[O:22][N:21]=1.[CH3:32][C:33](C)=O>>[Cl:19][C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([Cl:12])[C:14]=1[C:20]1[CH:24]=[C:23]([C:25]2[CH:30]=[C:29]([NH:31][CH2:32][CH2:33][C:3]([O:7][CH:8]([CH3:9])[CH3:10])=[O:11])[CH:28]=[CH:27][N:26]=2)[O:22][N:21]=1
2.5
null
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
705,450
CC(=O)[O-]
null
null
null
ord_dataset-c408dfed796e4354b61e312e67f7143f
2006-01-01T00:04:00
true
Ammonium acetate (26 g, 0.34 mol) was added to a solution of {4-[2-Oxo-2-(3-trifluoromethyl-phenyl)-ethylcarbamoyl]-cyclohexylmethyl}-carbamic acid benzyl ester (5.4 g, 0.0113 mol) in acetic acid. The resulting homogeneous mixture was refluxed overnight and then concentrated under reduced pressure. The residue was partitioned between 10% NaOH and EtOAc (1:1) and the EtOAc layer was washed with 10% NaOH (3×) and brine. The EtOAc was dried (Na2SO4) and concentrated under reduced pressure to give {4-[4-(3-Trifluoromethyl-phenyl)-1H-imidazol-2-yl]-cyclohexylmethyl}-carbamic acid benzyl ester. 1H NMR (CDCl3): δ 1.02–1.18 (m, 2H), 1.46–1.62 (m, 3H), 1.86–1.96 (m, 2H), 2.12–2.21 (m, 2H), 2.74 (m, 1H), 3.10 (t, J=6 Hz, 2H), 4.91 (t, 1H, N—H), 5.10 (s, 2H), 7.22 (s, 1H), 7.32–7.37 (m, 5H), 7.45 (d, J=4.9 hz, 2H), 7.87 (m, 1H), 7.95 (s, 1H). MS 458 (M+H)+
O=C(NCC1CCC(c2nc(-c3cccc(C(F)(F)F)c3)c[nH]2)CC1)OCc1ccccc1
null
O=C(NCC1CCC(C(=O)NCC(=O)c2cccc(C(F)(F)F)c2)CC1)OCc1ccccc1
[NH4+]
null
C([O-])(=O)C.[NH4+:5].[CH2:6]([O:13][C:14](=[O:39])[NH:15][CH2:16][CH:17]1[CH2:22][CH2:21][CH:20]([C:23](=O)[NH:24][CH2:25][C:26](=O)[C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=2)[CH2:19][CH2:18]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C(O)(=O)C>[CH2:6]([O:13][C:14](=[O:39])[NH:15][CH2:16][CH:17]1[CH2:22][CH2:21][CH:20]([C:23]2[NH:24][CH:25]=[C:26]([C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=3)[N:5]=2)[CH2:19][CH2:18]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
null
CC(=O)O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,456,517
O=C([O-])[O-]
[Na+]
null
null
ord_dataset-a86112d52cd54525a5e36d41f18aced2
2014-01-01T00:07:00
true
2-Chloro-3-fluoropyridine (0.4380 g, 3.33 mmol), 4-chlorophenylboronic acid (0.6248 g, 3.996 mmol), palladium tetrakistriphenylphosphine (0.1924 g, 0.1665 mmol), sodium carbonate (0.4235 g, 3.996 mmol), toluene (10 mL), and water (1 mL) were placed in a teflon lined vial. The vial was sealed and stirred at 125° C. for 21 hour. The mixture was cooled to ambient temperature and the whole mixture was purified on silica gel (EtOAc-hexanes gradient) to provide 569.4 mg of the title compound as white solid (82%).
Fc1cccnc1-c1ccc(Cl)cc1
null
OB(O)c1ccc(Cl)cc1
Fc1cccnc1Cl
null
Cl[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[Cl:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>O>[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:2]2[C:7]([F:8])=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:12][CH:11]=1
21
Cc1ccccc1
O
null
125
82.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
22,236
[Al+3]
[Cl-]
null
null
ord_dataset-19b9e29d593f4660ab77c07b459da9bb
1977-01-01T00:04:00
true
In a most preferred embodiment of the process of this invention, a solution of 0.05 equivalents of the isatin derivative, 0.06 mole equivalents of the carbanilide, and 0.30 moles of aluminum chloride in 200 ml. of nitrobenzene are maintained at 100° C for about 12 hours. The cooled solution is poured into one liter of ice water and 600 ml. of hexane to precipitate the product. After filtering, the product is suspended in 200 ml. of acetic acid, 5 ml. of water, and 20 ml. of sulfuric acid. This solution is refluxed for approximately 24 hours, cooled and filtered. This refluxing hydrolyzes the reacted anilide and yields the desired oxindole diamine derivative. The filtrate containing the oxindole diamine derivative is neutralized with sodium carbonate and the solution concentrated in vacuo and taken in about 300 ml. of boiling 1N hydrochloric acid. This solution is diluted in about 300 ml. of water, cooled to about 5° C, filtered, and made basic with ammonia to precipitate the product. The product is collected and may be recrystallized from a dioxane hexane solution to yield the pure oxindole diamine derivative.
NC1C(=O)N(N)c2ccccc21
null
O=C1Nc2ccccc2C1=O
O=C(Nc1ccccc1)Nc1ccccc1
O=[N+]([O-])c1ccccc1
[NH:1]1[C:11]2C(=CC=CC=2)C(=O)C1=O.C1C=CC(N[C:19]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:20])=CC=1.[Cl-].[Al+3].[Cl-].[Cl-].[N+:32](C1C=CC=CC=1)([O-])=O>>[N:21]1([NH2:32])[C:22]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:11]([NH2:1])[C:19]1=[O:20]
null
null
null
null
0
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
786,444
CC[SiH](CC)CC
null
null
null
ord_dataset-4ad5db8537994579bef51f16dd8bf0bd
2007-01-01T00:08:00
true
A 50 mL single-neck round bottom flask was charged with ethyl 6-acetyl-2-(trifluoromethyl)-2H-chromene-3-carboxylate (1.465 g, 4.662 mmole), dichloromethane (4 mL), and triethyl silane (1.71 mL, 1.25 g, 10.72 mmole) and stirred at RT overnight. The crude reaction was poured into water and extracted several times with dichloromethane. The combined organics were washed with water, then with aqueous 10% sodium carbonate solution, dried over MgSO4, filtered and concentrated in vacuo to yield a colorless oil. This oil was purified by silica chromatography (9 hexane: 1 ethyl acetate) yielding the title compound as a clear, colorless oil (1.25 g, 89%): 1H NMR (acetone-d6/300 MHz) 7.84 (s, 1H), 7.30 (d, 1H, J=2.0 Hz), 7.26 (dd, 1H, J=8.3, 2.0 Hz), 6.93 (d, 1H, J=8.3 Hz), 5.79 (q, 1H, J=7.3 Hz), 4.37-4.24 (m, 2H), 2.60 (q, 2H, J=7.6 Hz), 1.32 (t, 3H, J=7.3 Hz), 1.20 (t, 3H, J=7.6 Hz). GCMS m/z 300 (M+).
CCOC(=O)C1=Cc2cc(CC)ccc2OC1C(F)(F)F
null
CCOC(=O)C1=Cc2cc(C(C)=O)ccc2OC1C(F)(F)F
null
null
[C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[O:10][CH:9]([C:14]([F:17])([F:16])[F:15])[C:8]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:7]2)(=O)[CH3:2].ClCCl.C([SiH](CC)CC)C>O>[CH2:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[O:10][CH:9]([C:14]([F:15])([F:16])[F:17])[C:8]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:7]2)[CH3:2]
8
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
1,517,009
null
null
null
null
ord_dataset-8c74302143c04eb9983e4b3a7ead2d72
2014-01-01T00:12:00
true
To a suspension of methyl 2-(6-oxo-4-phenyl-2-(piperidin-1-yl)-1,6-dihydropyrimidin-5-yl)pentanoate (1.74 g; 4,71 mmol) in dry toluene (10 mL) under nitrogen atmosphere were carefully added phosphorus oxychloride (4.38 mL; 47.1 mmol) and dimethylaniline (0.476 mL; 3.77 mmol) and the reaction mixture was heated to reflux for 3 h. The volatiles were removed under reduced pressure (while the reaction mixture was still at elevated temperature), the residue was cooled in an ice-bath and quenched by adding crushed ice and a saturated solution of sodium hydrogen carbonate until neutralization. The aqueous layer was extracted with ethyl acetate, the organics were collected, dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (1-10%) in heptane furnished 0.040 g (1.6%, over 3 last steps) of the title compound as a yellow oil.
CCCC(C(=O)OC)c1c(Cl)nc(N2CCCCC2)nc1-c1ccccc1
null
O=P(Cl)(Cl)Cl
CCCC(C(=O)OC)c1c(-c2ccccc2)nc(N2CCCCC2)[nH]c1=O
null
O=[C:2]1[NH:7][C:6]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[N:5][C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:3]1[CH:20]([CH2:25][CH2:26][CH3:27])[C:21]([O:23][CH3:24])=[O:22].P(Cl)(Cl)([Cl:30])=O.CN(C)C1C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:30][C:2]1[C:3]([CH:20]([CH2:25][CH2:26][CH3:27])[C:21]([O:23][CH3:24])=[O:22])=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[N:7]=1
null
Cc1ccccc1
CN(C)c1ccccc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,655,007
Br
null
null
null
ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0
2015-01-01T00:11:00
true
(R)-4-methoxy-2-(2-(methoxymethyl)pyrrolidin-1-yl)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidine (96 mg, 0.20 mmol) was dissolved in AcOH (3 mL) and then 48% hydrobromic acid (0.1 mL) was added. The mixture was heated at 90° C. FOR 3.5 hours. The mixture was concentrated and the residue was treated with NaHCO3 solution. The solution was extracted with EtOAc (3×) and the organic was washed with NaHCO3, dried over Na2SO4, filtered and concentrated to obtain the crude. The material was treated with ether and sonicated. The solid was filtered, washed with ether and dried under vacuum to obtain (R)-2-(2-(methoxymethyl)pyrrolidin-1-yl)-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-4(3H)-one (58 mg, 60.1% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.15 (br s, 1H), 8.73 (s, 1H), 8.36 (d, J=5.7 Hz, 1H), 8.28 (br s, 1H), 8.26 (s, 1H), 7.97 (s, 1H), 7.53 (m, 1H), 7.23 (d, J=2.4 Hz, 1H), 6.62 (m, 1H), 4.34 (m, 1H), 3.85 (s, 3H), 3.52-3.40 (m, 4H), 3.28 (s, 3H), 2.35 (s, 3H), 1.95 (br d, J=27.5 Hz, 4H); MS (ESI) m/z: 474.3 (M+H+).
COC[C@H]1CCCN1c1ncc(-c2ccc(Oc3ccnc(-c4cnn(C)c4)c3)c(C)n2)c(=O)[nH]1
null
COC[C@H]1CCCN1c1ncc(-c2ccc(Oc3ccnc(-c4cnn(C)c4)c3)c(C)n2)c(OC)n1
null
null
C[O:2][C:3]1[C:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]4[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=4)[CH:17]=3)=[C:11]([CH3:28])[N:10]=2)=[CH:7][N:6]=[C:5]([N:29]2[CH2:33][CH2:32][CH2:31][C@@H:30]2[CH2:34][O:35][CH3:36])[N:4]=1.Br.CCOCC>CC(O)=O>[CH3:36][O:35][CH2:34][C@H:30]1[CH2:31][CH2:32][CH2:33][N:29]1[C:5]1[NH:4][C:3](=[O:2])[C:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([C:22]4[CH:23]=[N:24][N:25]([CH3:27])[CH:26]=4)[CH:17]=3)=[C:11]([CH3:28])[N:10]=2)=[CH:7][N:6]=1
3.5
CC(=O)O
CCOCC
null
90
61.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,413,542
null
null
null
null
ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f
2014-01-01T00:04:00
true
(S)-tert-butoxycarbonylamino-cyclohexyl-acetic acid cyclopentyl ester (1.17 g, 3.60 mmol) was dissolved in a TFA/DCM mixture (1:1, 10 ml) at 0° C. The solution was stirred for 90 minutes, the solvent removed in vacuo. The residue was azetroped with a DCM/heptane mixture (2×) to give a gum. The gum was redissolved in DCM (10 ml) and washed with saturated aqueous NaHCO3 solution (3×10 ml), dried (MgSO4) and filtered. The solvent of the filtrate was removed in vacuo to give the product as an oil (0.780 g, 78% yield). 1H NMR (300 MHz, CDCl3), δ: 1.00-1.40 (10H, m, CH×10), 1.50-2.00 (8H, m, CH×8), 3.25 (1H, d, CH, J=7.2Hz), 5.20 (1H, m, CH).
N[C@H](C(=O)OC1CCCC1)C1CCCCC1
null
CC(C)(C)OC(=O)N[C@H](C(=O)OC1CCCC1)C1CCCCC1
null
null
[CH:1]1([O:6][C:7](=[O:23])[C@@H:8]([NH:15]C(OC(C)(C)C)=O)[CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH2:5][CH2:4][CH2:3][CH2:2]1>C(O)(C(F)(F)F)=O.C(Cl)Cl.C(Cl)Cl>[CH:1]1([O:6][C:7](=[O:23])[C@@H:8]([NH2:15])[CH:9]2[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]2)[CH2:5][CH2:4][CH2:3][CH2:2]1
1.5
ClCCl
O=C(O)C(F)(F)F
null
null
96.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,700,303
null
null
null
null
ord_dataset-54347fcace774f89850681d6dec8009f
2016-01-01T00:03:00
true
The title compound was prepared in an analogous fashion to that described in Example 75 using (S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 78.1) and 2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine to afford an off-white solid. UPLC-MS (condition 1) tR=2.30 min, m/z=499.0 [M+H]+, m/z=497.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 0.90-1.04 (m, 4H) 1.49-1.62 (m, 1H) 1.77-1.88 (m, 1H) 2.10-2.19 (m, 1H) 2.18-2.26 (m, 1H) 2.99 (dd, J=11.00, 6.85 Hz, 1H) 3.09-3.20 (m, 2H) 3.21-3.29 (m, 1H) 3.29-3.41 (m, 2H) 4.60 (br. s, 1H) 7.29-7.40 (m, 3H) 7.64 (dd, J=8.07, 2.20 Hz, 1H) 7.85 (d, J=9.05 Hz, 2H) 7.99 (d, J=2.20 Hz, 1H) 8.45 (d, J=2.20 Hz, 1H) 8.73 (d, J=2.20 Hz, 1H) 10.14 (s, 1H).
O=C(Nc1ccc(OC(F)(F)F)cc1)c1cnc(N2CC[C@H](CO)C2)c(-c2ccc(C3CC3)nc2)c1
null
O=C(Nc1ccc(OC(F)(F)F)cc1)c1cnc(N2CC[C@H](CO)C2)c(Br)c1
CC1(C)OB(c2ccc(C3CC3)nc2)OC1(C)C
null
Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@H:24]([CH2:27][OH:28])[CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[CH:29]1([C:32]2[CH:37]=[CH:36][C:35](B3OC(C)(C)C(C)(C)O3)=[CH:34][N:33]=2)[CH2:31][CH2:30]1>>[CH:29]1([C:32]2[N:33]=[CH:34][C:35]([C:2]3[C:3]([N:22]4[CH2:26][CH2:25][C@H:24]([CH2:27][OH:28])[CH2:23]4)=[N:4][CH:5]=[C:6]([C:7]([NH:9][C:10]4[CH:11]=[CH:12][C:13]([O:16][C:17]([F:19])([F:18])[F:20])=[CH:14][CH:15]=4)=[O:8])[CH:21]=3)=[CH:36][CH:37]=2)[CH2:31][CH2:30]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
1,254,029
Cl[Ti](Cl)(Cl)Cl
null
null
null
ord_dataset-c544c0c663f54dbea4ddb52ddde7934e
2013-01-01T00:01:00
true
8-Methoxy-3,4-dihydro-1H-quinolin-2-one (5 g) was dissolved in dichloromethane (100 ml), and dichloromethyl methyl ether (6.4 ml) was added at room temperature, followed by cooling in an ice water bath. Titanium tetrachloride (85 ml) was added dropwise at a temperature not higher than 10° C., and the resulting mixture was stirred at room temperature overnight. The reaction mixture was poured into ice water, and the aqueous layer was subjected to extraction with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Diethyl ether was added to the residue and the produced solid was collected by filtration and dried to thereby obtain 5.2 g (yield: 90%) of 8-methoxy-2-oxo-1,2,3,4-tetrahydroquinoline-5-carboxaldehyde.
COc1ccc(C=O)c2c1NC(=O)CC2
null
COC(Cl)Cl
COc1cccc2c1NC(=O)CC2
null
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[NH:11][C:10](=[O:13])[CH2:9][CH2:8]2.[CH3:14][O:15]C(Cl)Cl>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[C:12]2[NH:11][C:10](=[O:13])[CH2:9][CH2:8][C:7]=2[C:6]([CH:14]=[O:15])=[CH:5][CH:4]=1
8
ClCCl
null
null
25
90
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
570,424
[H-]
[Na+]
null
null
ord_dataset-5e1b2445a3d94ea592ddf2c284118a1e
2002-01-01T00:11:00
true
A solution of 11 g (0.0617 mol) of benzofuran-2,3-dione dioxime in 50 ml of dimethylformamide is added dropwise to a suspension of 2.4 g (0.06 mol) of 60% strength sodium hydride in 25 ml of dimethylformamide, and stirring is effected at 20° C. for one hour. 7.55 g (0.06 mol) of dimethyl sulphate are then added dropwise and stirring is continued at 20° C. for a further 16 hours. The reaction mixture is poured into water and the resulting mixture is extracted with ethyl acetate, the organic phase is dried over sodium sulphate and concentrated under reduced pressure. The residue is chromatographed over silica gel using hexane/acetone (7:3). Stirring the residue with diethyl ether affords 0.7 g of benzofuran-2,3-dione3-(O-methyl-oxime)2-oxime (VIII-1) as a mixture of stereoisomers consisting of 90.6% of isomer A and 9% of isomer B (HPLC).
CON=C1C(=NO)Oc2ccccc21
null
ON=C1Oc2ccccc2C1=NO
COS(=O)(=O)OC
null
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3](=[N:10][OH:11])[C:2]1=[N:12][OH:13].[H-].[Na+].S(OC)(O[CH3:20])(=O)=O.O>CN(C)C=O>[CH3:20][O:11][N:10]=[C:3]1[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[O:1][C:2]1=[N:12][OH:13]
1
CN(C)C=O
O
null
null
6.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,744,898
COc1cccc2c1CC[C@H](C)N2
null
null
null
ord_dataset-60a3e71da3174666a50a61dcfa611a9f
2016-01-01T00:07:00
true
(S)-8-Fluoro-5-methoxy-2-methyl-1,2,3,4-tetrahydroquinoline was synthesized from 8-fluoro-5-methoxy-2-methylquinoline according to the procedures described above for (2S)-5-methoxy-2-methyl-1,2,3,4-tetrahydroquinoline (Intermediate 1). MS (ESI, pos. ion) m/z 196 [M+H]+.
COc1ccc(F)c2c1CC[C@H](C)N2
null
COc1ccc(F)c2nc(C)ccc12
null
null
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:13][CH3:14])=[C:6]2[C:11]=1[N:10]=[C:9]([CH3:12])[CH:8]=[CH:7]2.COC1C=CC=C2C=1CC[C@H](C)N2>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:13][CH3:14])=[C:6]2[C:11]=1[NH:10][C@@H:9]([CH3:12])[CH2:8][CH2:7]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
1,336,039
CC(=O)O[BH-](OC(C)=O)OC(C)=O
O=C([O-])O
[Na+]
null
ord_dataset-08852243bba44cb28769a5833f1515fe
2013-01-01T00:09:00
true
To 10 mL of a chloroform solution containing 226 mg of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one and 150 mg of 2,2-difluorobenzo[1,3]dioxol-5-carbaldehyde, 43 μL of acetic acid was added, and stirred at room temperature for 1 hour. To the reaction mixture, 257 mg of sodium triacetoxyborohydride was added, and stirred for 2.5 hours. To the reaction mixture, aqueous saturated sodium hydrogen carbonate solution was added, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [Silica Gel; Kanto Chemical Co., Inc., Silica Gel 60, eluent; chloroform:methanol=10:1] to give 188 mg of 1-(2-(4-((2,2-difluorobenzo[1,3]dioxol-5-yl)methylamino)piperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one as a pale yellow solid.
COc1ccc2ncc(=O)n(CCN3CCC(NCc4ccc5c(c4)OC(F)(F)O5)CC3)c2c1
null
COc1ccc2ncc(=O)n(CCN3CCC(N)CC3)c2c1
O=Cc1ccc2c(c1)OC(F)(F)O2
null
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[F:23][C:24]1([F:35])[O:28][C:27]2[CH:29]=[CH:30][C:31]([CH:33]=O)=[CH:32][C:26]=2[O:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(O)(=O)C.C(Cl)(Cl)Cl>[F:35][C:24]1([F:23])[O:28][C:27]2[CH:29]=[CH:30][C:31]([CH2:33][NH:1][CH:2]3[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]4[C:19]5[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=5)[N:13]=[CH:12][C:11]4=[O:22])[CH2:6][CH2:7]3)=[CH:32][C:26]=2[O:25]1
1
ClC(Cl)Cl
CC(=O)O
null
25
53.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
988,116
Cl
O=C([O-])[O-]
[K+]
null
ord_dataset-35b56288528641309a040cc2b6710b61
2010-01-01T00:08:00
true
Add potassium carbonate (40 mg, 0.29 mmol) and bromoethanol (0.018 mL, 0.26 mmol) to a solution of (S)-9-[(3,5-Bis-trifluoromethyl-benzyl)-(2H-tetrazol-5-yl)-amino]-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylic acid isopropyl ester (50 mg, 0.086 mmol) in dimethylformamide (0.3 mL). Stir at room temperature for 18 hrs in a sealed tube. Then add bromoethanol (0.018 mL, 0.26 mmol) and stir for 2 hrs. Add a 1N solution of hydrochloric acid and extract with dichloromethane. Dry the organic phase over anhydrous sodium sulfate, filter and concentrate in vacuo. Purify the residue using silica gel cartridge, eluting with ethyl acetate/hexanes to afford the title compound (26 mg, 49%). MS (ES+): 627 (M+H).
CC(C)OC(=O)N1CCC[C@H](N(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2nnn(CCO)n2)c2cc3c(cc21)CCC3
null
CC(O)Br
CC(C)OC(=O)N1CCC[C@H](N(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c2nn[nH]n2)c2cc3c(cc21)CCC3
null
C(=O)([O-])[O-].[K+].[K+].Br[CH:8]([OH:10])[CH3:9].[CH:11]([O:14][C:15]([N:17]1[C:30]2[C:22](=[CH:23][C:24]3[CH2:25][CH2:26][CH2:27][C:28]=3[CH:29]=2)[C@@H:21]([N:31]([CH2:37][C:38]2[CH:43]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:41]=[C:40]([C:48]([F:51])([F:50])[F:49])[CH:39]=2)[C:32]2[N:33]=[N:34][NH:35][N:36]=2)[CH2:20][CH2:19][CH2:18]1)=[O:16])([CH3:13])[CH3:12].Cl>CN(C)C=O>[CH:11]([O:14][C:15]([N:17]1[C:30]2[C:22](=[CH:23][C:24]3[CH2:25][CH2:26][CH2:27][C:28]=3[CH:29]=2)[C@@H:21]([N:31]([CH2:37][C:38]2[CH:39]=[C:40]([C:48]([F:49])([F:50])[F:51])[CH:41]=[C:42]([C:44]([F:45])([F:46])[F:47])[CH:43]=2)[C:32]2[N:33]=[N:34][N:35]([CH2:9][CH2:8][OH:10])[N:36]=2)[CH2:20][CH2:19][CH2:18]1)=[O:16])([CH3:13])[CH3:12]
18
CN(C)C=O
null
null
25
null
48.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
598,594
null
null
null
null
ord_dataset-843ef38b45484f72826f5f39d8a29c4d
2003-01-01T00:06:00
true
The product from Example 305G and ethyl glycolate were processed as described in Example 62A to provide the title compound.
CCOC(=O)COc1cc(Oc2ccc(CN(Cc3ccc(F)cc3F)c3cccc([N+](=O)[O-])c3C)cc2)ccc1F
null
CCOC(=O)CO
Cc1c(N(Cc2ccc(Oc3ccc(F)c(O)c3)cc2)Cc2ccc(F)cc2F)cccc1[N+](=O)[O-]
null
[F:1][C:2]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:3]=1[CH2:4][N:5]([CH2:16][C:17]1[CH:31]=[CH:30][C:20]([O:21][C:22]2[CH:23]=[CH:24][C:25]([F:29])=[C:26]([OH:28])[CH:27]=2)=[CH:19][CH:18]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[C:7]=1[CH3:15].[C:37]([O:41][CH2:42][CH3:43])(=[O:40])[CH2:38]O>>[F:1][C:2]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:3]=1[CH2:4][N:5]([CH2:16][C:17]1[CH:31]=[CH:30][C:20]([O:21][C:22]2[CH:23]=[CH:24][C:25]([F:29])=[C:26]([CH:27]=2)[O:28][CH2:38][C:37]([O:41][CH2:42][CH3:43])=[O:40])=[CH:19][CH:18]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[C:7]=1[CH3:15]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
870,253
O=C([O-])O
[Na+]
null
null
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
2009-01-01T00:03:00
true
A mixture of 2-bromo-4′-methylacetophenone (152 mg, 0.7 mmol) and 4-bromobenzamide (200 mg, 1.0 mmol) was heated to 160° C. for 3 hours, cooled to room temperature, dissolved in ethyl acetate (20 mL), and treated with 5% sodium bicarbonate (20 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×10 mL). The combined extracts were dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 50% ethyl acetate/hexanes to provide the desired product. MS (DCI) m/e 314, 316 (M−H)−, (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 8.70 (s, 1H), 8.00-7.97 (m, 2H), 7.79-7.76 (m, 2H), 7.77-7.74 (m, 2H), 7.29-7.27 (m, 2H), 2.34 (s, 31).
Cc1ccc(-c2coc(-c3ccc(Br)cc3)n2)cc1
null
Cc1ccc(C(=O)CBr)cc1
NC(=O)c1ccc(Br)cc1
null
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=1)=O.[Br:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][CH:14]=1.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[Br:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]2[O:18][CH:2]=[C:3]([C:5]3[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][CH:6]=3)[N:19]=2)=[CH:15][CH:14]=1
null
CCOC(C)=O
null
null
160
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
938,660
null
null
null
null
ord_dataset-90b0aa1f83334a02919b2be3a1c04542
2010-01-01T00:02:00
true
3-Bromo-benzoic acid (112 mg, 0.56 mmol) was coupled with ethyl ester (6) (100 mg, 0.56 mmol) following Method C to give the title compound.
CCOC(=O)Cc1cccc(NC(=O)c2cccc(Br)c2)c1
null
CCOC(=O)Cc1cccc(N)c1
O=C(O)c1cccc(Br)c1
null
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=O.[CH2:11]([O:13][C:14](=[O:23])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([NH2:22])[CH:17]=1)[CH3:12]>>[CH2:11]([O:13][C:14](=[O:23])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([NH:22][C:5](=[O:7])[C:4]2[CH:8]=[CH:9][CH:10]=[C:2]([Br:1])[CH:3]=2)[CH:17]=1)[CH3:12]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,343,500
null
null
null
null
ord_dataset-6034127657614f02860ed057b62b882e
2013-01-01T00:10:00
true
The compound is prepared by the reaction of 1-bromo-6-(3-hydroxyphenyl)-naphthalene-2-ol (100 mg, 0.32 mmol, 1 eq) with N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide (94.3 mg, 0.32 mmol, 1 eq) according to method A in 2 h. Purification by column chromatography with hexane/ethyl acetate 3/2 yields the desired compound in a yield of 64%, 83 mg.
CS(=O)(=O)Nc1cccc(-c2c(O)ccc3cc(-c4cccc(O)c4)ccc23)c1
null
Oc1cccc(-c2ccc3c(Br)c(O)ccc3c2)c1
CC1(C)OB(c2cccc(NS(C)(=O)=O)c2)OC1(C)C
null
Br[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([OH:18])[CH:13]=3)=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[OH:19].CC1(C)C(C)(C)OB([C:28]2[CH:29]=[C:30]([NH:34][S:35]([CH3:38])(=[O:37])=[O:36])[CH:31]=[CH:32][CH:33]=2)O1>>[OH:19][C:3]1[CH:4]=[CH:5][C:6]2[C:11](=[CH:10][CH:9]=[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([OH:18])[CH:13]=3)[CH:7]=2)[C:2]=1[C:28]1[CH:29]=[C:30]([NH:34][S:35]([CH3:38])(=[O:36])=[O:37])[CH:31]=[CH:32][CH:33]=1
2
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
30,846
null
null
null
null
ord_dataset-56c07ce5503b46d1805bdf471f8f1c55
1977-01-01T00:10:00
true
534 mg. (3 mmol.) of N-bromosuccinimide (recrystallized from water) were added in small portions to a solution of 831 mg. (3 mmol.) of 3-acetyl-2,6-di-t-butylamino-4-methylpyridine (Compound V) in 20 ml. of carbon tetrachloride and 5 ml. of ethanol, and the reaction mixture was allowed to stand overnight at room temperature. The reaction mixture was evaporated down at reduced pressure, and the residue was partitioned between ether and water. The organic phase was dried over anhydrous sodium sulfate and evaporated at reduced pressure to obtain yellow crystals. Recrystallization from methanol/water gave the product (990 mg.), m.p. 99°-100° C.
CC(=O)c1c(NC(C)(C)C)nc(NC(C)(C)C)c(Br)c1C
null
O=C1CCC(=O)N1Br
CC(=O)c1c(C)cc(NC(C)(C)C)nc1NC(C)(C)C
null
[Br:1]N1C(=O)CCC1=O.[C:9]([C:12]1[C:13]([NH:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[N:14][C:15]([NH:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:16][C:17]=1[CH3:18])(=[O:11])[CH3:10].C(Cl)(Cl)(Cl)Cl>C(O)C>[C:9]([C:12]1[C:13]([NH:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[N:14][C:15]([NH:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[C:16]([Br:1])[C:17]=1[CH3:18])(=[O:11])[CH3:10]
8
ClC(Cl)(Cl)Cl
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
462,017
O=C([O-])[O-]
[I-]
[K+]
null
ord_dataset-5ca9db262dd24c5a9315cdc8ef055b7e
2000-01-01T00:04:00
true
A mixture of ethyl 4-(4-methylphenyl)-4-piperidine carboxylate (3.0 g, 0.012 mol, prepared similarly as described in the method in Pol. Pat. 105 435 or Ber. 74, 1433 (1941)), 5-(3-bromo-1-propylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (4.50 g, 0.0145 mol), anhydrous potassium carbonate (5.00 g, 0.036 mol) and potassium iodide (4.0 g, 0.024 mol) in 2-butanone (100 ml) was stirred at 80° C. for 7.5 h. The mixture was diluted with ether (150 ml) and water (150 ml) and the layers were separated. The aqueous phase was extracted with additional ether (80 ml) and the combined organic extracts were washed with water (100 ml) and dried (MgSO4). The solvent was removed in vacuo and the oily residue (6.60 g) was purified by gradient column chromatography on silica gel using mixtures of benzene and ethyl acetate as eluents. The benzene/ethyl acetate (9:1) fraction afforded 2.90 g (50%) of 4-(4-methylphenyl)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-4-piperidinecarboxylic acid ethyl ester.
CCOC(=O)C1(c2ccc(C)cc2)CCN(CCC=C2c3ccccc3CCc3ccccc32)CC1
null
BrCCC=C1c2ccccc2CCc2ccccc21
CCOC(=O)C1(c2ccc(C)cc2)CCNCC1
null
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Br[CH2:20][CH2:21][CH:22]=[C:23]1[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[CH2:27][CH2:26][C:25]2[CH:34]=[CH:35][CH:36]=[CH:37][C:24]1=2.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(=O)CC.CCOCC.O>[CH2:17]([O:16][C:14]([C:8]1([C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)[CH2:9][CH2:10][N:11]([CH2:20][CH2:21][CH:22]=[C:23]2[C:24]3[CH:37]=[CH:36][CH:35]=[CH:34][C:25]=3[CH2:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]2=3)[CH2:12][CH2:13]1)=[O:15])[CH3:18]
null
O
CCOCC
CCC(C)=O
null
50
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,088,731
null
null
null
null
ord_dataset-52a37d876ddb453e86de0c15fa233d29
2011-01-01T00:09:00
true
A mixture of the compound (2.12 g) obtained in Step 4 and 2-bromo-3-oxobutyric acid tert-butyl ester (2.0 g) in acetonitrile (20 ml) was stirred at 80° C. for 30 min. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned by adding ethyl acetate and saturated aqueous sodium carbonate solution. The organic layer was washed successively with saturated aqueous sodium carbonate solution and saturated brine, dried over anhydrous sodium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate:n-hexane=1:2) to give the title compound (1.82 g).
Cc1nc(N2CCN(S(=O)(=O)c3ccc(OC(F)(F)F)cc3)[C@@H](C(=O)OCc3ccccc3)C2)sc1C(=O)OC(C)(C)C
null
NC(=S)N1CCN(S(=O)(=O)c2ccc(OC(F)(F)F)cc2)[C@@H](C(=O)OCc2ccccc2)C1
CC(=O)C(Br)C(=O)OC(C)(C)C
null
[CH2:1]([O:8][C:9]([C@H:11]1[CH2:16][N:15]([C:17](=[S:19])[NH2:18])[CH2:14][CH2:13][N:12]1[S:20]([C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=1)(=[O:22])=[O:21])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:34]([O:38][C:39](=[O:45])[CH:40](Br)[C:41](=O)[CH3:42])([CH3:37])([CH3:36])[CH3:35]>C(#N)C>[CH2:1]([O:8][C:9]([C@H:11]1[CH2:16][N:15]([C:17]2[S:19][C:40]([C:39]([O:38][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:45])=[C:41]([CH3:42])[N:18]=2)[CH2:14][CH2:13][N:12]1[S:20]([C:23]1[CH:24]=[CH:25][C:26]([O:29][C:30]([F:33])([F:31])[F:32])=[CH:27][CH:28]=1)(=[O:21])=[O:22])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
0.5
CC#N
null
null
80
67.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,128,008
F[P-](F)(F)(F)(F)F
null
null
null
ord_dataset-285df12e34cd46e993e3c8ebc3a8962a
2012-01-01T00:01:00
true
A mixture of (1R,10R,11S,16S)-1,11,15,15-tetramethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3,5-dicarboxylic acid (85) (0.07 g, 0.2 mmol), HATU (0.25 g, 0.65 mmol) and 4-methylmorpholine (0.07 mL, 1 mmol) in THF (10 mL) and DMF (2.0 mL) was stirred at room temperature for 18 h in a sealed vessel. The mixture was concentrated under reduced pressure and the residue was triturated with water. The resulting solid was collected by filtration to give (1R,10R,11S,16S)-1,3-N,5-N,11,15,15-hexamethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3,5-dicarboxamide (86) (0.035 g, 47%) as a white solid. 1H NMR (CD3OD): δ 8.38 (d, 1H), 7.88 (d, 1H), 3.54 (m, 2H), 2.90 (d, 6H), 2.67 (d, 1H), 2.18 (d, 1H), 1.90-1.48 (m, 9H), 1.46-1.14 (m, 3H), 1.06-0.93 (m, 4H), 0.90 (s, 3H), 0.87 (s, 3H). MS m/z 461 (C25H36N2O4S+H+).
CNC(=O)c1cc(C(=O)NC)c2c(c1)S(=O)(=O)C[C@@H]1[C@@]3(C)CCCC(C)(C)[C@@H]3CC[C@@]21C
null
CC1(C)CCC[C@]2(C)[C@H]3CS(=O)(=O)c4cc(C(=O)O)cc(C(=O)O)c4[C@]3(C)CC[C@@H]12
CN1CCOCC1
CN(C)C(On1nnc2cccnc21)=[N+](C)C
[CH3:1][C@@:2]12[CH2:19][CH2:18][C@@H:17]3[C@:12]([CH3:22])([CH2:13][CH2:14][CH2:15][C:16]3([CH3:21])[CH3:20])[C@H:11]1[CH2:10][S:9](=[O:24])(=[O:23])[C:8]1[C:3]2=[C:4]([C:28]([OH:30])=O)[CH:5]=[C:6]([C:25](O)=[O:26])[CH:7]=1.[CH3:31][N:32](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:55][N:56]1CCOCC1>C1COCC1.CN(C=O)C>[CH3:1][C@@:2]12[CH2:19][CH2:18][C@@H:17]3[C@:12]([CH3:22])([CH2:13][CH2:14][CH2:15][C:16]3([CH3:21])[CH3:20])[C@H:11]1[CH2:10][S:9](=[O:24])(=[O:23])[C:8]1[C:3]2=[C:4]([C:28]([NH:56][CH3:55])=[O:30])[CH:5]=[C:6]([C:25]([NH:32][CH3:31])=[O:26])[CH:7]=1
18
C1CCOC1
CN(C)C=O
null
25
38
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
916,558
[BH4-]
[Na+]
null
null
ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d
2009-01-01T00:11:00
true
NaBH4 (5.2 g) was added to a stirred solution of 4,5-dichlorophthalic anhydride (20 g) in anhydrous DMF (100 mL) at 0° C. under nitrogen in small portions over 1 hour. The reaction was warmed to room temperature for a further 2 hours and poured into ice/1M HCl. The resultant white precipitate (4,5-dichloro-2-hydroxymethyl-benzoic acid) was collected by filtration and dried under vacuum. The precipitate was suspended in toluene (200 mL) with catalytic pTSA and heated to reflux under Dean-Stark conditions (precipitate dissolves on heating) for 18 hours. The reaction was cooled to room temperature and the resultant white precipitate collected by filtration to give the sub-title compound as a white solid (14.0 g, 75%); 1H NMR (400 MHz, d6-DMSO) δ 5.40 (2H, s), 8.05 (1H, s), 8.15 (1H, s).
O=C1OCc2cc(Cl)c(Cl)cc21
null
O=C1OC(=O)c2cc(Cl)c(Cl)cc21
null
null
[BH4-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]2[C:11](=O)[O:10][C:8](=[O:9])[C:7]2=[CH:13][C:14]=1[Cl:15]>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[C:6]2[C:7](=[CH:13][C:14]=1[Cl:15])[C:8](=[O:9])[O:10][CH2:11]2
null
CN(C)C=O
null
null
25
74.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,108,145
null
null
null
null
ord_dataset-375a420ee9b042918ddca20f02df37d3
2011-01-01T00:11:00
true
The process is carried out as in Example 80 above, with the compound from Example 60B, 6-acetyl-3-(4-bromophenyl)-1,9-dimethyl-1,9-dihydropyrido[2,3-b]indol-2-one and diethyl oxalate.
CCOC(=O)C(=O)CC(=O)c1ccc2c(c1)c1cc(-c3ccc(Br)cc3)c(=O)n(C)c1n2C
null
CCOC(=O)C(=O)OCC
CC(=O)c1ccc2c(c1)c1cc(-c3ccc(Br)cc3)c(=O)n(C)c1n2C
null
[C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[C:8]1[N:14]([CH3:26])[C:15](=[O:25])[C:16]([C:18]3[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][CH:19]=3)=[CH:17][C:7]2=1)(=[O:3])[CH3:2].[C:27](OCC)(=[O:33])[C:28]([O:30][CH2:31][CH3:32])=[O:29]>>[CH2:31]([O:30][C:28](=[O:29])[C:27](=[O:33])[CH2:2][C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:13])[C:8]1[N:14]([CH3:26])[C:15](=[O:25])[C:16]([C:18]3[CH:19]=[CH:20][C:21]([Br:24])=[CH:22][CH:23]=3)=[CH:17][C:7]2=1)=[O:3])[CH3:32]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
548,891
CC(C)COC(=O)Cl
CCN1CCOCC1
null
null
ord_dataset-e967d076b4894c2c854795f019ed3c39
2002-01-01T00:06:00
true
2 g of 1-(N-(tert-butoxycarbonyl)-2(S)-amino-butyryl)-L-proline (6.6 mmol) prepared as in Example 2 c) are dissolved in tetrahydrofuran (40 ml). 0.86 ml of isobutyl chloroformate (6.6 mmol) and 0.85 ml of N.-ethylmorpholine (6.6 mmol) are then added to this solution, at −10° C. and under nitrogen. After stirring at −10° C. for 20 minutes, 2.75 ml of n-propylamine (33.0 mmol) are added. The mixture is left stirring at 0° C. for one hour and then at room temperature overnight. The solvent is evaporated off under vacuum and a white semi-solid material is obtained. It is dissolved in ethyl acetate (150 ml) and washed with 5% citric acid (30 ml), saturated sodium bicarbonate solution (30 ml) and brine (20 ml). After drying (Na2SO4) the mixture is filtered and the solvent is evaporated off. An oil is obtained, which is purified by liquid chromatography on a column (eluent: ethyl acetate) and a white solid is obtained.
CCCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CC)NC(=O)OC(C)(C)C
null
CCCN
CC[C@H](NC(=O)OC(C)(C)C)C(=O)N1CCC[C@H]1C(=O)O
null
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:20][CH3:21])[C:10]([N:12]1[CH2:19][CH2:18][CH2:17][C@H:13]1[C:14]([OH:16])=O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(OCC(C)C)=O.C(N1CCOCC1)C.[CH2:38]([NH2:41])[CH2:39][CH3:40]>O1CCCC1.C(OCC)(=O)C>[CH2:38]([NH:41][C:14](=[O:16])[C@@H:13]1[CH2:17][CH2:18][CH2:19][N:12]1[C:10](=[O:11])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:20][CH3:21])[CH2:39][CH3:40]
0.33
C1CCOC1
CCOC(C)=O
null
-10
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,372,793
Cl
null
null
null
ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81
2013-01-01T00:12:00
true
To the product from step 1 (91 mg, 0.246 mmol) was added 4M HCl in dioxane (6 mL) and the resulting mixture was stirred at rt for 3 h. The solvent was removed in vacuo to obtain the product as a oil (63 mg, 95%); MS; m/z 270 (M+H): LCMS (UV) 99%; 1H NMR (400 MHz, DMSO-d6) δ 1.71-1.78 (m, 1H), 1.89-2.0 (m, 2H), 2.1-2.15 (m, 1H), 3.16-3.24 (m, 2H), 3.88-3.93 (m, 1H), 4.11-4.15 (dd, 1H J1=8.4 Hz, J2=10.8 Hz), 4.22-4.26 (dd, 1H J1=3.6 Hz, J2=10.8 Hz), 6.91-6.94 (m, 2H), 7.03 (s, 3H), 7.06-7.1 (m, 1H), 7.34-7.38 (m, 2H)
c1ccc(Oc2ccc(OC[C@H]3CCCN3)cc2)cc1
null
CC(C)(C)OC(=O)N1CCC[C@@H]1COc1ccc(Oc2ccccc2)cc1
null
null
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=O)(C)(C)C.Cl>O1CCOCC1>[O:21]([C:18]1[CH:19]=[CH:20][C:15]([O:14][CH2:13][C@H:9]2[CH2:10][CH2:11][CH2:12][NH:8]2)=[CH:16][CH:17]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
3
C1COCCO1
null
null
25
95.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
707,217
Cl
null
null
null
ord_dataset-c8069773c1a148aca8ab417108daacc5
2006-01-01T00:05:00
true
Made using the same procedure as for [4-(2,4-dichlorophenyl)-5-pyrazolylpyrimidin-2-yl]{2-[(5-nitro(2-pyridyl))amino]ethyl}amine dihydrochloride except that 2-benzimidazolyl-1-(2,4-dichlorophenyl)-3-(dimethylamino)prop-2-en-1-one (XIV, 468 mg, 1.3 mmol) was used and the crude product was purified by recrystallization (CH2Cl2/Et2O/hexanes).
O=[N+]([O-])c1ccc(NCCNc2ncc(-c3nc4ccccc4[nH]3)c(-c3ccc(Cl)cc3Cl)n2)nc1
null
CN(C)C=C(C(=O)c1ccc(Cl)cc1Cl)c1nc2ccccc2[nH]1
O=[N+]([O-])c1ccc(NCCNc2ncc(-c3cc[nH]n3)c(-c3ccc(Cl)cc3Cl)n2)nc1
null
Cl.Cl.[Cl:3][C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1[C:11]1[C:16]([C:17]2C=CN[N:18]=2)=[CH:15][N:14]=[C:13]([NH:22][CH2:23][CH2:24][NH:25][C:26]2[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][N:27]=2)[N:12]=1.[N:35]1[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=2NC=1C(=CN(C)C)C(C1C=CC([Cl:53])=CC=1Cl)=O>>[ClH:3].[ClH:53].[N:18]1[C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[NH:35][C:17]=1[C:16]1[C:11]([C:5]2[CH:6]=[CH:7][C:8]([Cl:10])=[CH:9][C:4]=2[Cl:3])=[N:12][C:13]([NH:22][CH2:23][CH2:24][NH:25][C:26]2[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][N:27]=2)=[N: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
1,256,093
O=C(Cl)C/C=C/c1ccccc1
[N-]=[N+]=NCCN
null
null
ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0
2013-01-01T00:02:00
true
As in the synthesis of N-(2-azidoethyl)tetradecanamide, (E)-4-phenylbut-3-enoyl chloride (0.198 g, 1.19 mmol) was reacted with 2-azidoethanamine (0.114 g, 1.19 mmol) and triethylamine (0.239 g, 2.37 mmol) in dichloromethane (5 mL) to give (E)-N-(2-azidoethyl)-4-phenylbut-3-enamide (0.168 g, 55%). 1H NMR (300 MHz, CDCl3) δ 7.68 (d, 1H), δ 7.45 (d, 2H), δ 7.29 (m, 3H), δ 7.04 (t, 1H), δ 6.59 (d, 1H), δ 3.55 (q, 2H), δ 3.47 (t, 2H) ppm; 13C NMR (75 MHz, CDCl3) δ 166.9, 141.6, 134.9, 130.1, 129.1, 128.1, 120.8, 51.1, 39.4 ppm; HRMS (ESI) calcd for C11H12N4O (M+) 216.1011, found 216.1005.
[N-]=[N+]=NCCNC(=O)C/C=C/c1ccccc1
null
CCCCCCCCCCCCCC(=O)NCCN=[N+]=[N-]
null
null
[N:1]([CH2:4][CH2:5][NH:6][C:7](=[O:21])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]CCCC)=[N+:2]=[N-:3].C1(/C=C/CC(Cl)=O)C=CC=CC=1.N(CCN)=[N+]=[N-].C(N(CC)CC)C>ClCCl>[N:1]([CH2:4][CH2:5][NH:6][C:7](=[O:21])[CH2:8]/[CH:9]=[CH:10]/[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[N+:2]=[N-:3]
null
ClCCl
CCN(CC)CC
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
888,923
null
null
null
null
ord_dataset-d728a2f811c0424cbcdb5a84d02b93ae
2009-01-01T00:06:00
true
To a solution of methyl(2S)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoate (3.26 g, 19.0 mmol) was added hydrazine monohydrate (2.1 ml). The mixture was heated at 130° C. for 90 min and cooled down to room temperature. After evaporation to dryness, the residue was purified on a small bed of silica gel (100% EtOAc) to afford the title compound.
C[C@](O)(C(=O)NN)C(F)(F)F
null
COC(=O)[C@](C)(O)C(F)(F)F
NN
null
[F:1][C:2]([F:11])([F:10])[C@:3]([OH:9])([CH3:8])[C:4](OC)=[O:5].O.[NH2:13][NH2:14]>>[F:1][C:2]([F:11])([F:10])[C@:3]([OH:9])([CH3:8])[C:4]([NH:13][NH2:14])=[O:5]
null
O
null
null
130
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,674,063
CC(C)COC(=O)Cl
N
null
null
ord_dataset-9cc455db05a444779921f786a45b21a6
2015-01-01T00:12:00
true
To a solution of 1-phenyl-1H-1,2,3-triazole-5-carboxylic acid (1.0 g, 5.6 mmol) and 4-methylmorpholine (0.57 g, 5.6 mmol) in 1,2-dimethoxyethane (5 mL), isobutyl chloroformate (0.77, 5.6 mmol) was added to the mixture. After 30 minutes, ammonia in dioxane (16.8 mL, 8.4 mmol) was added to the reaction. Then it was stirred overnight. The solvent was removed and dissolved in 50 mL of ethyl acetate. The organic layer was washed with brine twice. The organic layer was dried with Na2SO4, filtered and concentrated and used without further purification. MS (m/z) 189 [M+H]+.
NC(=O)c1cnnn1-c1ccccc1
null
CN1CCOCC1
O=C(O)c1cnnn1-c1ccccc1
null
[C:1]1([N:7]2[C:11]([C:12]([OH:14])=O)=[CH:10][N:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[N:16]1CCOCC1.ClC(OCC(C)C)=O.N.O1CCOCC1>COCCOC>[C:1]1([N:7]2[C:11]([C:12]([NH2:16])=[O:14])=[CH:10][N:9]=[N:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
0.5
COCCOC
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
null
29,681
Cl
[Na+]
[OH-]
null
ord_dataset-dc78376bd0a946d1a5a41eec30282b7d
1977-01-01T00:09:00
true
The quinoline (30g), hydroxylamine hydrochloride (14g), sodium hydroxide (9g), ethanol (165ml) and water (65ml) were stirred and refluxed for 2 hours. Water (100ml) was added and the product was allowed to crystallise overnight. The crystals were removed by filtration and washed with water and dried to give 3-methyl-8-oximino-5,6,7,8-tetrahydroquinoline (27.5g) mp 188° C.
Cc1cnc2c(c1)CCCC2=NO
null
NO
Cc1cnc2c(c1)CCCC2=O
null
[CH3:1][C:2]1[CH:3]=[N:4][C:5]2[C:6](=O)[CH2:7][CH2:8][CH2:9][C:10]=2[CH:11]=1.Cl.[NH2:14][OH:15].[OH-].[Na+].C(O)C>O>[CH3:1][C:2]1[CH:3]=[N:4][C:5]2[C:6](=[N:14][OH:15])[CH2:7][CH2:8][CH2:9][C:10]=2[CH:11]=1
null
CCO
O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
755,745
O=C([O-])[O-]
[Cs+]
null
null
ord_dataset-1b0cd79134f0450eaac8396a4f956c30
2007-01-01T00:02:00
true
3-(4-Hydroxyphenyl)-2-methyl-2-phenoxypropionic acid ethyl ester (495 mg, 1.7 mmol) (see Ex. 1, Part C), toluene-4-sulfonic acid 2-[5-methyl-2-(3-thiophen-3-ylphenyl)oxazol-4-yl]ethyl ester (2.2 mmol) and Cs2CO3 (700 mg, 2.2 mmol) are combined in anhydrous DMF (25 mL) and stirred for 16 h at 55° C. under an atmosphere of nitrogen. The mixture was then cooled and diluted with ethyl acetate (100 mL), and washed with water then brine. The organic layer was dried with Na2SO4 and concentrated in vacuo to a viscous yellow oil. The residue was purified by flash column chromatography (100 g silica, 60×15 mL fractions, gradient elution 0–20% ethyl acetate in hexanes) to provide the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.23 (s, 1H), 7.90 (dt, J=7.6 Hz, J=1.2 Hz, 1H), 7.64 (dt, J=7.6 Hz, J=1.2 Hz, 1H), 7.56–7.55 (m, 1H), 7.48–7.39 (m, 3H), 7.23–7.14 (m, 5H), 6.96 (t, J=7.2 Hz, 1H), 6.83–6.81 (m, 4H), 4.24 (t, J=6.8 Hz, 2H), 4.12 (q, J=7.2 Hz, 2H), 3.26 (d, J=14.0 Hz, 1H), 3.10 (d, J=14.0 Hz, 1H), 3.00 (t, J=6.4 Hz, 2H), 2.39 (s, 3H), 1.38 (s, 3H) 1.21 (t, J=7.2 Hz, 3H); MS (EI) 568.2 (M+H)+.
CCOC(=O)C(C)(Cc1ccc(OCCc2nc(-c3cccc(-c4ccsc4)c3)oc2C)cc1)Oc1ccccc1
null
CCOC(=O)C(C)(Cc1ccc(O)cc1)Oc1ccccc1
Cc1ccc(S(=O)(=O)OCCc2nc(-c3cccc(-c4ccsc4)c3)oc2C)cc1
null
[CH2:1]([O:3][C:4](=[O:22])[C:5]([CH3:21])([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)[CH3:2].[CH3:23][C:24]1[O:28][C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]3[CH:39]=[CH:38][S:37][CH:36]=3)[CH:30]=2)=[N:26][C:25]=1[CH2:40][CH2:41]OS(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:22])[C:5]([CH3:21])([O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:41][CH2:40][C:25]2[N:26]=[C:27]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([C:35]4[CH:39]=[CH:38][S:37][CH:36]=4)[CH:30]=3)[O:28][C:24]=2[CH3:23])=[CH:9][CH:8]=1)[CH3:2]
16
CCOC(C)=O
CN(C)C=O
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
1,178,614
null
null
null
null
ord_dataset-0f9d2dbe929a45c3892ae75e81e99443
2012-01-01T00:06:00
true
The title compound was prepared following procedure described for example 35, step 1, but starting from Intermediate 36 (1 135.37 mg; 4.20 mmol) and Intermediate 1 (891.15 mg; 4.20 mmol). The reaction mixture was cooled to RT and concentrated affording yellow oil. It was precipitating in ACN. Solvent were removed and the solid was washed with MeOH, filtered off and dried under vacuum to afford the title compound as a white powder. 1H NMR (CDCl3) δ 8.43 (s, 1H), 8.18-7.99 (m, 4H), 7.41-7.35 (m, 3H), 7.29-7.24 (m, 1H), 7.11 (d, J=7.2 Hz, 1H), 4.27-4.17 (m, 2H), 3.98 (s, 3H), 3.34 (s, 3H), 2.50-2.28 (m, 2H), 1.05 (t, J=7.5 Hz, 3H). LC/MS (Method B): 447.2 (M+H)+. HPLC (Method A) Rt 6.14 min (Purity: 99.5%).
CCc1ccccc1-c1ccc(-c2nc(-c3ccc(C(=O)OC)c(F)c3)no2)cc1COC
null
CCc1ccccc1-c1ccc(C(=O)O)cc1COC
COC(=O)c1ccc(C(N)=NO)cc1F
null
[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15](O)=O)=[CH:11][C:10]=1[CH2:18][O:19][CH3:20])[CH3:2].[NH2:21][C:22](=[N:34][OH:35])[C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]([F:33])[CH:24]=1>>[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:35][N:34]=[C:22]([C:23]3[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[C:25]([F:33])[CH:24]=3)[N:21]=2)=[CH:11][C:10]=1[CH2:18][O:19][CH3:20])[CH3:2]
null
null
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
49,232
CC(C)CCON=O
Cl
null
null
ord_dataset-0bb2e99daa66408fb8dbd6a0781d241c
1978-01-01T00:12:00
true
To a stirred solution of 7.49 g. of N-benzyloxycarbonyl-L-seryl-L-tyrosyl hydrazide [this compound is reported in Helv. Chim. Acta, 41, 1852 (1958)] in 50 ml. of N,N-dimethylformamide, cooled to -30° C., is first added 16.9 ml. of 3.607 N hydrogen chloride in tetrahydrofuran and then 2.7 ml. of isoamyl nitrite, and the resulting mixture is stirred at -30° C. for 30 minutes. The mixture, which contains N-benzyloxycarbonyl-L-seryl-L-tyrosyl azide, is next cooled to -60° C., and to it are added first 8.57 ml. of triethylamine, then 4.297 g. of glycyl-L-leucine methyl ester hydrochloride and finally 2.52 ml. more of triethylamine. The stirred mixture is allowed to warm to 0° C. during one hour and is stirred at 0° C. for one hour and kept at -5° C. for 48 hours. It is then filtered, and the filtrate is evaporated under reduced pressure at 40°-50° C. The gummy residue is partitioned between dilute hydrochloric acid and ethyl acetate, and the organic layer is separated, washed with saturated aqueous sodium bicarbonate and with saturated aqueous sodium chloride, dried, and evaporated to give a solid residue of N-benzyloxycarbonyl-L-seryl-L-tyrosylglycyl-L-leucine methyl ester; m.p. 166°-167° C., following two crystallizations from ethyl acetate-ether; [α]D25 -25.4° (2% in N,N-dimethylformamide); [α]D25 -38.2° (2.09% in methanol).
COC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)OCc1ccccc1
null
[N-]=[N+]=NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)OCc1ccccc1
COC(=O)[C@H](CC(C)C)NC(=O)CN
null
Cl.N(OCCC(C)C)=O.[CH2:10]([O:17][C:18]([NH:20][C@H:21]([C:24]([NH:26][C@H:27]([C:36]([N:38]=[N+]=[N-])=[O:37])[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=1)=[O:25])[CH2:22][OH:23])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.Cl.[CH3:42][O:43][C:44](=[O:55])[C@H:45]([CH2:51][CH:52]([CH3:54])[CH3:53])[NH:46][C:47](=[O:50])[CH2:48]N>O1CCCC1.C(N(CC)CC)C.CN(C)C=O>[CH3:42][O:43][C:44](=[O:55])[C@H:45]([CH2:51][CH:52]([CH3:53])[CH3:54])[NH:46][C:47](=[O:50])[CH2:48][NH:38][C:36](=[O:37])[C@H:27]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=1)[NH:26][C:24](=[O:25])[C@H:21]([CH2:22][OH:23])[NH:20][C:18]([O:17][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:19]
1
CN(C)C=O
CCN(CC)CC
C1CCOC1
-60
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,161,379
[Br-]
[H-]
[Na+]
null
ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880
2012-01-01T00:05:00
true
To a solution of diethyl methylmalonate (5.19 g) in 100 mL of THF was added NaH (1.2 g, 60%) at 0° C. in portions. The mixture was stirred at 0° C. for 10 min, and to this solution was then added the bromide intermediate (3.84 g) in one portion. The mixture was warmed to 23° C. and stirred for 1 h before the addition of water. The resulting mixture was extracted with ethyl acetate, concentrated and purified by Biotage (5-10% ethyl acetate in hexane) to give the diester containing some diethyl methyl malonate contaminant as a crude oil.
CCOC(=O)C(CC)C(=O)OC
null
CCOC(=O)C(C)C(=O)OCC
C1CCOC1
null
[CH3:1][CH:2]([C:8]([O:10][CH2:11]C)=[O:9])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[Br-].O.[CH2:17]1COCC1>>[CH3:17][CH2:1][CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:8]([O:10][CH3:11])=[O:9]
0.17
O
null
null
0
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
471,454
Cl[Ti](Cl)(Cl)Cl
null
null
null
ord_dataset-cd531114850e4f239b2a3661044ae672
2000-01-01T00:08:00
true
To a solution of 17.7 g of the 2-ethyl-2,4,5,7-tetramethylindane in 100 ml of dry dichloromethane was continuously added 9.5 ml of α,α-dichloromethyl methyl ether and 11.6 ml of TiCl4 at 0° C. The reaction mixture was stirred at room temperature for 2 hours, quenched with 200 ml of water, and separated the organic layer. The aqueous layer was extracted with dichloromethane. The combined organic layer was dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography to afford 18.26 g of the title compound as brown solid.
CCC1(C)Cc2c(C)c(C)c(C=O)c(C)c2C1
null
COC(Cl)Cl
CCC1(C)Cc2c(C)cc(C)c(C)c2C1
null
[CH2:1]([C:3]1([CH3:15])[CH2:11][C:10]2[C:5](=[C:6]([CH3:14])[CH:7]=[C:8]([CH3:13])[C:9]=2[CH3:12])[CH2:4]1)[CH3:2].[CH3:16][O:17]C(Cl)Cl>ClCCl.Cl[Ti](Cl)(Cl)Cl>[CH2:1]([C:3]1([CH3:15])[CH2:11][C:10]2[C:5](=[C:6]([CH3:14])[C:7]([CH:16]=[O:17])=[C:8]([CH3:13])[C:9]=2[CH3:12])[CH2:4]1)[CH3:2]
2
ClCCl
null
null
25
90
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
755,881
null
null
null
null
ord_dataset-1b0cd79134f0450eaac8396a4f956c30
2007-01-01T00:02:00
true
A solution of methanesulphonic anhydride (8.33 g, 47.8 mmol) in dichloromethane (30 ml) was added dropwise over 30 minutes to an ice-cooled solution of (R)-2-butanol (4.0 ml, 43.5 mmol) and triethylamine (6.65 ml, 47.8 mmol) in dichloromethane (70 ml). The reaction was then allowed to warm to room temperature and stirred for 18 hours. The mixture was then washed with water, 2N hydrochloric acid, then dried (Na2SO4) and evaporated under reduced pressure to give the title compound as a pale yellow oil, 7.0 g.
CC[C@@H](C)OS(C)(=O)=O
null
CS(=O)(=O)OS(C)(=O)=O
CC[C@@H](C)O
null
[CH3:1][S:2]([O:5]S(C)(=O)=O)(=[O:4])=[O:3].[CH3:10][C@@H:11](O)[CH2:12][CH3:13].C(N(CC)CC)C>ClCCl>[CH3:1][S:2]([O:5][C@H:11]([CH3:10])[CH2:12][CH3:13])(=[O:4])=[O:3]
18
CCN(CC)CC
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
417,979
[Al+3]
[H-]
[Li+]
null
ord_dataset-94e21e9990034c729ea727e7d2ab0eb0
1998-01-01T00:12:00
true
1840 mg of (2R,4R)-1-ethoxycarbonyl-4-hydroxy-2-{2-[6-methyl-2-(2-phenylethyl)phenoxy]ethyl}pyrrolidine [prepared as described in step (b) above], 20 ml of tetrahydrofuran and 530 mg of lithium aluminum hydride were allowed to react together and subsequently treated in the same manner as described in step (b) of Example 1. The concentrated substance thus obtained was purified by silica gel column chromatography, using a 5:1 by volume mixture of methylene chloride and methanol as the eluent, to give 1050 mg (yield 67%) of the title compound as a colorless solid substance.
Cc1cccc(CCc2ccccc2)c1OCC[C@@H]1C[C@@H](O)CN1C
null
CCOC(=O)N1C[C@H](O)C[C@H]1CCOc1c(C)cccc1CCc1ccccc1
null
null
C(O[C:4]([N:6]1[CH2:10][C@H:9]([OH:11])[CH2:8][C@H:7]1[CH2:12][CH2:13][O:14][C:15]1[C:20]([CH3:21])=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[OH:11][C@H:9]1[CH2:10][N:6]([CH3:4])[C@H:7]([CH2:12][CH2:13][O:14][C:15]2[C:20]([CH3:21])=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:8]1
null
C1CCOC1
null
null
null
null
66.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
598,946
null
null
null
null
ord_dataset-82e842e611ef4a05b6e7f9ea0a46d52d
2003-01-01T00:07:00
true
A mixture of (R)-7-ethoxymethyl-1-(5-hydroxyhexyl)-8-mercapto-3-methylxanthine (0.19 g, 0.533 mmol) potassium carbonate (0.15 g, 10.7 mmol) and 1-bromo-2-chloroethane (114 mg, 0.80 mmol) in acetonitrile (10 ml) was stirred at 65° C. for 1.5 hours. After concentrating under reduced pressure, the residue was purified by column chromatography on silica gel eluting with ethyl acetate-hexane (1:1) to provide (R)-7-ethoxymethyl-8-(2-chloroethylsulfanyl)-1-(5-hydroxyhexyl)-3-methylxanthine (150 mg, 67% yield) as a white powder.
CCOCn1c(SCCCl)nc2c1c(=O)n(CCCC[C@@H](C)O)c(=O)n2C
null
ClCCBr
CCOCn1c(S)nc2c1c(=O)n(CCCC[C@@H](C)O)c(=O)n2C
null
[CH2:1]([O:3][CH2:4][N:5]1[C:13]2[C:12](=[O:14])[N:11]([CH2:15][CH2:16][CH2:17][CH2:18][C@H:19]([OH:21])[CH3:20])[C:10](=[O:22])[N:9]([CH3:23])[C:8]=2[N:7]=[C:6]1[SH:24])[CH3:2].Br[CH2:26][CH2:27][Cl:28]>C(#N)C>[CH2:1]([O:3][CH2:4][N:5]1[C:13]2[C:12](=[O:14])[N:11]([CH2:15][CH2:16][CH2:17][CH2:18][C@H:19]([OH:21])[CH3:20])[C:10](=[O:22])[N:9]([CH3:23])[C:8]=2[N:7]=[C:6]1[S:24][CH2:26][CH2:27][Cl:28])[CH3:2]
1.5
CC#N
null
null
65
null
67.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,689,561
Br[Mg]CCC1CC1
II
[Mg]
null
ord_dataset-c1e70ad912eb438f8d34b1dc681f809a
2016-01-01T00:02:00
true
Magnesium metal (39.0 mg, 2.0 mmol) and iodine (one crystal) was taken up in dry diethyl ether (1.2 mL) and (2-bromoethyl)cyclopropane (200 mg, 1.3 mmol) was added dropwise until iodine color faded. The remainder was then added dropwise over 15 minutes to maintain a gentle reflux and then cooled to 0° C. (2-cyclopropylethyl)magnesium bromide (1.1 M, 0.38 mL, 0.41 mmol) was added to a cooled (0° C.) solution of (6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)(pyridin-2-yl)methanone (50 mg, 0.14 mmol) in dry THF (1.0 mL) under argon and allowed to stir for 10 minutes. The reaction was quenched with water, extracted three times with EtOAc, and combined organic layers were concentrated and purified by reverse-phase HPLC to give 3-cyclopropyl-1-(6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-1H-benzo[d]imidazol-4-yl)-1-(pyridin-2-yl)propan-1-ol intermediate. The intermediate was taken up in EtOH (1.5 mL) and 0.2 mL concentrated HCl and heated to 65° C. for 2 hours and concentrated to afford the desired product as a white powder.
CCOc1nc2c(C(O)(CCC3CC3)c3ccccn3)cc(-c3c(C)noc3C)cc2[nH]1
null
BrCCC1CC1
CCOc1nc2c(C(=O)c3ccccn3)cc(-c3c(C)noc3C)cc2[nH]1
null
[Mg].II.Br[CH2:5][CH2:6][CH:7]1[CH2:9][CH2:8]1.C1(CC[Mg]Br)CC1.[CH3:17][C:18]1[C:22]([C:23]2[CH:24]=[C:25]([C:35]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=3)=[O:36])[C:26]3[N:30]=[C:29]([O:31][CH2:32][CH3:33])[NH:28][C:27]=3[CH:34]=2)=[C:21]([CH3:43])[O:20][N:19]=1>C(OCC)C.C1COCC1>[CH:7]1([CH2:6][CH2:5][C:35]([C:25]2[C:26]3[N:30]=[C:29]([O:31][CH2:32][CH3:33])[NH:28][C:27]=3[CH:34]=[C:23]([C:22]3[C:18]([CH3:17])=[N:19][O:20][C:21]=3[CH3:43])[CH:24]=2)([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=2)[OH:36])[CH2:9][CH2:8]1
0.17
CCOCC
C1CCOC1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
335,834
null
null
null
null
ord_dataset-65c44df6676d4ce3a1874db5d7958ca9
1996-01-01T00:08:00
true
In accordance with the general procedure described in Example 1, reaction of 10 g (0.055 mol) of 3-dimethylamino-(3-thienyl)-2-propen-1-one [described in EP-A-0 233 461] and 15 g (0.060 mol) of 3-(1,1,2,2-tetrafluoroethoxy)phenylguanidine nitrate gives N-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-4-(3-thienyl)-2-pyrimidine-amine; FAB-MS:370 (M+ +1), m.p. 110°-111°, Rf =0.8 (ethyl acetate:hexane=1:1).
FC(F)C(F)(F)Oc1cccc(Nc2nccc(-c3ccsc3)n2)c1
null
CN(C)C=CC(=O)c1ccsc1
N=C(N)Nc1cccc(OC(F)(F)C(F)F)c1
null
CN(C)[CH:3]=[CH:4][C:5]([C:7]1[CH:11]=[CH:10][S:9][CH:8]=1)=O.[N+]([O-])(O)=O.[F:17][C:18]([F:33])([O:22][C:23]1[CH:24]=[C:25]([NH:29][C:30]([NH2:32])=[NH:31])[CH:26]=[CH:27][CH:28]=1)[CH:19]([F:21])[F:20]>>[F:17][C:18]([F:33])([O:22][C:23]1[CH:24]=[C:25]([NH:29][C:30]2[N:32]=[C:5]([C:7]3[CH:11]=[CH:10][S:9][CH:8]=3)[CH:4]=[CH:3][N:31]=2)[CH:26]=[CH:27][CH:28]=1)[CH:19]([F:20])[F:21]
null
O=[N+]([O-])O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,687,187
null
null
null
null
ord_dataset-c1e70ad912eb438f8d34b1dc681f809a
2016-01-01T00:02:00
true
6-Bromo-5-(2,4-difluorophenyl)-1,2,4-triazin-3-amine (0.13 g, 21%) was prepared from 5-(2,4-difluorophenyl)-1,2,4-triazin-3-amine (0.45 g, 2.1 mmol) and N-bromosuccinimide (0.49 g, 2.80 mmol) according to the general procedure of Preparation 3.
Nc1nnc(Br)c(-c2ccc(F)cc2F)n1
null
O=C1CCC(=O)N1Br
Nc1nncc(-c2ccc(F)cc2F)n1
null
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([NH2:15])[N:12]=[N:13][CH:14]=1.[Br:16]N1C(=O)CCC1=O>>[Br:16][C:14]1[N:13]=[N:12][C:11]([NH2:15])=[N:10][C:9]=1[C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1]
null
null
null
null
null
null
21.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,041,833
[Fe]
[Cl-]
[NH4+]
null
ord_dataset-3af92aec23dc4810b92eb0d8c60023ee
2011-01-01T00:03:00
true
The product from Example 255b was reduced with Fe and NH4Cl following the procedure from Example 9E to provide the title compound (980 mg, 90%).
Nc1cc(NC(=O)c2ccco2)ccc1Sc1ccc(O)cc1
null
O=C(Nc1ccc(Sc2ccc(O)cc2)c([N+](=O)[O-])c1)c1ccco1
null
null
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]3[O:19][CH:20]=[CH:21][CH:22]=3)=[O:17])=[CH:11][C:10]=2[N+:23]([O-])=O)=[CH:4][CH:3]=1.[NH4+].[Cl-]>[Fe]>[NH2:23][C:10]1[CH:11]=[C:12]([NH:15][C:16]([C:18]2[O:19][CH:20]=[CH:21][CH:22]=2)=[O:17])[CH:13]=[CH:14][C:9]=1[S:8][C:5]1[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=1
null
null
null
null
null
90
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
314,192
CC[O-]
[Na+]
null
null
ord_dataset-bd998d3fe946475e835418aaf647c00d
1995-01-01T00:08:00
true
Add 0.5 cm3 of a molar solution of sodium ethanolate in ethanol to a solution of 1 g (3.78 mmol) of ethyl 7-acetoxy-1,4-benzodioxin-2-carboxylate in 15 cm3 of anhydrous ethanol under a nitrogen atmosphere. Stir for 18 hours at room temperature and then neutralise with Dowex X-8 resin, acid form, which has been washed beforehand with ethanol. After filtration and concentration to dryness under partial pressure, the crude product obtained is purified by chromatography on a silica column (eluant: petroleum ether/diethyl ether, 80:20). Ethyl 7-hydroxy-1,4-benzodioxin-2-carboxylate is thereby obtained in a yield of 96%. Melting point: 160° C. ##STR43##
CCOC(=O)C1=COc2ccc(O)cc2O1
null
CCOC(=O)C1=COc2ccc(OC(C)=O)cc2O1
null
null
C([O-])C.[Na+].C([O:8][C:9]1[CH:10]=[CH:11][C:12]2[O:17][CH:16]=[C:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[O:14][C:13]=2[CH:23]=1)(=O)C>C(O)C>[OH:8][C:9]1[CH:10]=[CH:11][C:12]2[O:17][CH:16]=[C:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[O:14][C:13]=2[CH:23]=1
18
CCO
null
null
25
96
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,662,644
CCCCCCCCc1ccc(NC(=O)NCCC(=O)OCC)cc1
null
null
null
ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0
2015-01-01T00:11:00
true
When the product of Step D was substituted for ethyl 3-(3-(4-octylphenyl)ureido)propanoate in Example 11, Step B, the identical process afforded the title compound in 84% yield, as a colourless solid. 1H-NMR (CDCl3) 7.68 (d, 1H, J=8.7 Hz); 6.94 (m, 2H); 5.24 (t, 1H, J=5.9 Hz); 3.86 (t, 2H, J=8.7 Hz); 3.58 (q, 2H, J=5.9 Hz); 3.11 (t, 2H, J=8.5 Hz); 2.67 (t, 2H, J=5.8 Hz); 2.5 (t, 2H, J=8 Hz); 1.54 (m, 2H); 1.25 (m, 10H); 0.86 (t, 3H, J=6.8 Hz).
CCCCCCCCc1ccc2c(c1)CCN2C(=O)NCCC(=O)O
null
CCCCCCCCc1ccc2c(c1)CCN2C(=O)NCCC(=O)OCC
null
null
[CH2:1]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:18]([NH:20][CH2:21][CH2:22][C:23]([O:25]CC)=[O:24])=[O:19])[CH2:13][CH2:12]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C(C1C=CC(NC(=O)NCCC(OCC)=O)=CC=1)CCCCCCC>>[CH2:1]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([C:18]([NH:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[O:19])[CH2:13][CH2:12]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
null
null
null
null
null
84
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
646,093
Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
I[Cu]I
null
null
ord_dataset-c975a50a7600448fabd558f4a94a3e29
2004-01-01T00:08:00
true
Under an argon atmosphere, 40 g (0.155 mol) of 9-bromoanthracene, 3.3 g (4.6 mmol) of bis(triphenylphosphine)palladium(II) dichloride and 0.87 g (3 mmol) of copper Iodide were dissolved in 500 ml of diisopropylamine in a 1 L 3-necked flask equipped with a stirrer, thermometer and reflux condenser. 23 g (0.233 mol) of trimethylsilyl acetylene was then slowly dropped into the resulting mixture at room temperature. The reaction mixture was slowly heated to 80° C. and refluxed for 12 hours. After the reaction was completed, the reaction mixture was cooled down to room temperature, and then the precipitated salt was filtered off. The solvent was removed under a reduced pressure, and then the residue was dissolved in methylene chloride. The organic layer was washed with water several times and then dried with anhydrous magnesium sulfate. The solvent was removed to obtain orange-colored liquid, which was purified by silica gel column chromatography using hexane as an eluent, and then recrystallized from ethanol to give yellow crystal. The yellow crystal was recovered and sufficiently dried in a vacuum oven at 40° C., to give 32 g (83.3% yield) of the desired product having a melting point of 66-68° C.
C#Cc1cccc2cc3ccccc3c([Si](C)(C)C)c12
null
C#C[Si](C)(C)C
Brc1c2ccccc2cc2ccccc12
null
Br[C:2]1[C:3]2[C:8]([CH:9]=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[CH3:16][Si:17]([C:20]#[CH:21])([CH3:19])[CH3:18]>C(NC(C)C)(C)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[CH3:16][Si:17]([CH3:19])([CH3:18])[C:20]1[C:4]2[C:3]([CH:2]=[C:15]3[C:21]=1[C:11]([C:10]#[CH:9])=[CH:12][CH:13]=[CH:14]3)=[CH:8][CH:7]=[CH:6][CH:5]=2
null
CC(C)NC(C)C
null
null
80
null
75.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,585,356
[Cl-]
[NH4+]
null
null
ord_dataset-380e279f82154dba9e08ab51b3bdd08a
2015-01-01T00:05:00
true
To a solution of tert-butyl-3-(3,5-difluorophenyl)-3-methoxypyrrolidin-1-carboxylate (2.64 g, 8.4 mmol) in methylene chloride (20 mL), was added trifluoroacetic acid (5 mL). The mixture was stirred for 1 h at ambient temperature after which aqueous saturated ammonium chloride solution (50 ml) was added and the aqueous phase was extracted with methylene chloride (2×50 mL). The combined organic phase was dried (Na2SO4), filtered and evaporated to give the crude product, purification on a Biotage Isolute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1) gave the title compound (1.3 g, 73%). MS m/z (rel. intensity, 70 eV) 213 (M+, 0.5), 183 (bp), 171 (89), 141 (80), 113 (88).
COC1(c2cc(F)cc(F)c2)CCNC1
null
COC1(c2cc(F)cc(F)c2)CCN(C(=O)OC(C)(C)C)C1
null
null
C(OC([N:8]1[CH2:12][CH2:11][C:10]([C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=2)([O:13][CH3:14])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[Cl-].[NH4+]>C(Cl)Cl>[F:22][C:17]1[CH:16]=[C:15]([C:10]2([O:13][CH3:14])[CH2:11][CH2:12][NH:8][CH2:9]2)[CH:20]=[C:19]([F:21])[CH:18]=1
null
O=C(O)C(F)(F)F
ClCCl
null
null
null
72.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
402,942
[Na]
null
null
null
ord_dataset-7fed188163cf4ccca934ec71504c7f8a
1998-01-01T00:05:00
true
There was dissolved 15.0 g (0.0604 mol) of 3-[3-(piperidinomethyl)phenoxy]propylamine in 150 ml of dichloromethane and added dropwise 6. 82 g (0.0604 mol) of chloroacetyl chloride under cooling with ice. After dropping, the mixture was stirred for 3.5 hours under cooling with ice and then the solvent was removed under reduced pressure. The residue was dissolved in 150 ml of ethanol and this solution was added to a solution which was prepared by adding 4.65 g (0.0604 mol) of 2-aminoethanethiol to a solution of 3.06 g (0.1329 mol) of sodium 150 ml of ethanol and stirring for 30 minutes at room temperature, and the obtained mixture was refluxed with heating for 3 hours. After being allowed to cool at room temperature, the precipitate was filtrated off, and the solvent was removed under reduced pressure. The obtained residue was dissolved in ethyl acetate and washed with water, and dried over Glauber's salt. Then the solvent was removed under reduced pressure to give 20.4 g of the titled compound as oily matter.
NCCSCC(=O)NCCCOc1cccc(CN2CCCCC2)c1
null
NCCS
O=C(Cl)CCl
NCCCOc1cccc(CN2CCCCC2)c1
[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:16]=[CH:17][CH:18]=2)[O:11][CH2:12][CH2:13][CH2:14][NH2:15])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[CH2:20][C:21](Cl)=[O:22].[NH2:24][CH2:25][CH2:26][SH:27].[Na]>ClCCl.C(O)C>[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:16]=[CH:17][CH:18]=2)[O:11][CH2:12][CH2:13][CH2:14][NH:15][C:21](=[O:22])[CH2:20][S:27][CH2:26][CH2:25][NH2:24])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
3.5
CCO
ClCCl
null
25
92.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
295,844
CS(=O)(=O)[O-]
[H-]
[Na+]
null
ord_dataset-ec7cb3d5a8704f64b01d401ea555974f
1994-01-01T00:09:00
true
A stirred mixture of 4-hydroxy-alpha-oxobenzeneacetic acid methyl ester (0.724 g) in dimethylformamide (10 mL) under argon was treated with 55% sodium hydride (0.175 g), stirred for 15 minutes and treated with the mesylate of 2-(3,4-dimethoxyphenoxy)ethanol (1.65 g). The mixture was heated at 60° C. overnight and worked up as in Example 20. The material was purified by HPLC (dichloromethane-diethyl ether, 99:1) and crystallized from dichloromethane-hexane to provide 0.9 g of 4-[[2-(3,4-dimethoxyphenoxy)ethyl]oxy]-alpha-oxobenzeneacetic acid methyl ester, mp 93°-94° C.
COC(=O)C(=O)c1ccc(OCCOc2ccc(OC)c(OC)c2)cc1
null
COC(=O)C(=O)c1ccc(O)cc1
COc1ccc(OCCO)cc1OC
null
[CH3:1][O:2][C:3](=[O:13])[C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1.[H-].[Na+].S([O-])(=O)(=O)C.[CH3:21][O:22][C:23]1[CH:24]=[C:25]([CH:30]=[CH:31][C:32]=1[O:33][CH3:34])[O:26][CH2:27][CH2:28]O>CN(C)C=O>[CH3:1][O:2][C:3](=[O:13])[C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:28][CH2:27][O:26][C:25]2[CH:30]=[CH:31][C:32]([O:33][CH3:34])=[C:23]([O:22][CH3:21])[CH:24]=2)=[CH:7][CH:6]=1
0.25
CN(C)C=O
null
null
60
62.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
660,273
Br
null
null
null
ord_dataset-04d607efe1d9485eb99fafa06880f62e
2005-01-01T00:02:00
true
A mixture of N-(4-chlorobenzyl)-2-(chloromethyl)-3,4-dimethyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide (100 mg, 0.25 mmol), 2-(methylamino)-1-pyridin-3-ylethanol hydrobromide (Arch. Pharm. 1961, 294 453-68)(89 mg, 0.38 mmol) and diisopropylethylamine (134 μL, 0.76 mmol) in dry DMF (5.0 mL) was stirred for 30 hours at room temperature. The solution was diluted with water (15 mL). The resulting milky suspension was stirred vigorously for 30 minutes, and then left standing overnight at room temp. The mixture was filtered, and the collected solid was washed with water and dried in vacuo, leaving a white solid. Recrystallization from acetonitrile (10 mL, dissolved with warming and then cooled to 0° C. overnight) gave the title compound (87 mg) as a white solid.
Cc1c(CN(C)CC(O)c2cccnc2)sc2c(=O)c(C(=O)NCc3ccc(Cl)cc3)cn(C)c12
null
CNCC(O)c1cccnc1
Cc1c(CCl)sc2c(=O)c(C(=O)NCc3ccc(Cl)cc3)cn(C)c12
null
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:23])[C:12]3[S:19][C:18]([CH2:20]Cl)=[C:17]([CH3:22])[C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.Br.[CH3:27][NH:28][CH2:29][CH:30]([C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1)[OH:31].C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:23])[C:12]3[S:19][C:18]([CH2:20][N:28]([CH2:29][CH:30]([OH:31])[C:32]4[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=4)[CH3:27])=[C:17]([CH3:22])[C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:24][CH:25]=1
30
O
CN(C)C=O
CCN(C(C)C)C(C)C
25
null
68.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
637,202
Cl
null
null
null
ord_dataset-a192df1b44174b5886ef2005f759d553
2004-01-01T00:05:00
true
0.10 g (0.20 mMol) 4-{4-methoxy-2-[(2-methoxy-pyridine-4-carbonyl)-amino]-benzothiazol-7-yl}-piperidine-1-carboxylic acid tert-butyl ester were dissolved in 2 ml 2.5 M HCl/MeOH and heated to reflux for 1.5 h. The reaction mixture was concentrated in vacuo and taken up in 3 ml isopropanol. The suspension formed was filtered and the material on the filter was washed with diethyl ether and dried in vacuo. One obtained 0.075 g (86%) 2-methoxy-N-(4-methoxy-7-piperidin-4-yl-benzothiazol-2-yl)-isonicotinamide 1:2 hydrochloride as a yellow solid. F.p.: 305-310° C.
COc1cc(C(=O)Nc2nc3c(OC)ccc(C4CCNCC4)c3s2)ccn1
null
COc1cc(C(=O)Nc2nc3c(OC)ccc(C4CCN(C(=O)OC(C)(C)C)CC4)c3s2)ccn1
null
null
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:22]3[S:21][C:20]([NH:23][C:24]([C:26]4[CH:31]=[CH:30][N:29]=[C:28]([O:32][CH3:33])[CH:27]=4)=[O:25])=[N:19][C:18]=3[C:17]([O:34][CH3:35])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C>Cl.CO>[CH3:33][O:32][C:28]1[CH:27]=[C:26]([CH:31]=[CH:30][N:29]=1)[C:24]([NH:23][C:20]1[S:21][C:22]2[C:14]([CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)=[CH:15][CH:16]=[C:17]([O:34][CH3:35])[C:18]=2[N:19]=1)=[O:25]
null
CO
null
null
null
94.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
546,206
O=S(=O)([O-])O
[K+]
null
null
ord_dataset-d31180f42ced44719fd9e72685c798bf
2002-01-01T00:05:00
true
First, 9.39 g of 4-(1-hydroxyethyl)-4′-(trans-4-pentylcyclohexyl)biphenyl, 0.52 g of potassium hydrogensulfate, and 50 ml of toluene were put in a 300 ml flask provided with a water content quantitative tube, and subjected to azeotropic dehydration under reflux for four hours. After the reaction, ether was added to the reaction solution, which was then washed with a saturated brine, and dried with sodium sulfate. The solvent was then distilled off. The residue was recrystallized from hexane to obtain 1.88 g (Y: 21.1%) of 4-(trans-4-pentylcyclohexyl)vinylbiphenyl. The purity of the resultant compound was 100.0% as measured by GC, 99.9% as measured by HPLC, and 1 spot as measured by TLC. The phase transfer temperature of the resultant compound was as follows.
CCCCC[C@H]1CC[C@H](C=Cc2ccc(-c3ccccc3)cc2)CC1
null
Cc1ccccc1
CCCCC[C@H]1CC[C@H](c2ccc(-c3ccc(C(C)O)cc3)cc2)CC1
null
OC([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([C@H:16]3CC[C@H](CCCCC)C[CH2:17]3)=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)C.S([O-])(O)(=O)=O.[K+].[C:33]1([CH3:39])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CCOCC>[CH2:39]([C@H:33]1[CH2:38][CH2:37][C@H:36]([CH:17]=[CH:16][C:13]2[CH:12]=[CH:11][C:10]([C:7]3[CH:8]=[CH:9][CH:4]=[CH:5][CH:6]=3)=[CH:15][CH:14]=2)[CH2:35][CH2:34]1)[CH2:9][CH2:4][CH2:5][CH3:6]
null
CCOCC
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,472,493
CNC
CS(=O)(=O)Cl
null
null
ord_dataset-fd1fa959d6264608b0b7fcda16741bfd
2014-01-01T00:08:00
true
To a solution of methyl 2-(hydroxymethyl)-2′-methylbiphenyl-4-carboxylate (2.12 g, 8.27 mmol) in DCM (65 mL) was added DIEA (7.03 mL, 41.4 mmol) and methanesulfonyl chloride (768 μL, 9.93 mmol) at 0° C. and stirred for 25 min. After this time, a 2M solution of dimethylamine in THF (12.4 mL, 24.8 mmol) was added and the resulting mixture was stirred at RT for 16 hours. The reaction mixture was partitioned between DCM and a 5N aqueous solution of NaOH. The organic layer was dried (MgSO4) and concentrated under vacuum. A purification by chromatography (silica, DCM/MeOH) gave the title compound as a light yellow solid (2.03 g, 86%). 1H NMR (DMSO-d6) δ 8.27 (d, J=1.4 Hz, 1H), 7.95 (dd, J=7.8, 1.9 Hz, 1H), 7.32-7.18 (m, 4H), 7.06 (d, J=7.3 Hz, 1H), 3.94 (s, 3H), 3.24-3.10 (m, 2H), 2.11 (s, 6H), 2.01 (s, 3H). HPLC (Method A) Rt 2.90 min (Purity 100.0%). LC/MS (Method B): 284.1 (M−H)−.
COC(=O)c1ccc(-c2ccccc2C)c(CN(C)C)c1
null
CCN(C(C)C)C(C)C
COC(=O)c1ccc(-c2ccccc2C)c(CO)c1
null
O[CH2:2][C:3]1[CH:8]=[C:7]([C:9]([O:11][CH3:12])=[O:10])[CH:6]=[CH:5][C:4]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19].C[CH2:21][N:22](C(C)C)[CH:23](C)C.CS(Cl)(=O)=O.CNC.C1COCC1>C(Cl)Cl>[CH3:21][N:22]([CH2:2][C:3]1[CH:8]=[C:7]([C:9]([O:11][CH3:12])=[O:10])[CH:6]=[CH:5][C:4]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])[CH3:23]
0.42
C1CCOC1
ClCCl
null
null
null
86.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
555,512
CC(C)(O)C#N
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
null
ord_dataset-ec9decb576c4424c9685993f6262bd9c
2002-01-01T00:07:00
true
Diethylazodicarboxylate (5.2 g) is added dropwise to a solution of 4-bromo-phenethylalcohol (2.01 g), and triphenylphosphine (7.9 g) in diethyl ether (16 mL) at 0° C. The reaction mixture is stirred for 10 minutes and a solution of acetone cyanohydrin (2.6 g) in diethyl ether (10 mL) is added. The clear orange solution is stirred for 5 minutes at 0° C. and then at 25° C. for 12 hours. The reaction mixture is then filtered, and washed with diethyl ether. The filtrate is concentrated under reduced pressure and chromatographed over silica gel (10% ethyl acetate-hexanes is used as the eluant) to provide the desired product as a pale yellow oil (2.04 g).
N#CCCc1ccc(Br)cc1
null
OCCc1ccc(Br)cc1
CCOC(=O)/N=N/C(=O)OCC
null
CCO[C:4](/[N:6]=N/C(OCC)=O)=O.[Br:13][C:14]1[CH:22]=[CH:21][C:17]([CH2:18][CH2:19]O)=[CH:16][CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)(O)C#N>C(OCC)C>[Br:13][C:14]1[CH:22]=[CH:21][C:17]([CH2:18][CH2:19][C:4]#[N:6])=[CH:16][CH:15]=1
0.17
CCOCC
null
null
null
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
321,565
O=[Pt]
null
null
null
ord_dataset-eed8d32c2f1d46a89ba39d04dfaa83b1
1995-01-01T00:12:00
true
5.3 gm of methyl 18-methyl-16-eicosenoate charged into an autoclave together with 0.3 gm of platinum oxide and 30 ml of acetic acid were reduced under 100 atm hydrogen pressure at 100° C. for 5 hours. After the reaction, the catalyst was removed by filtration and the solvent was evaporated to obtain 3 gm of methyl 18-methyleicosanoate, which was purified by flash column chromatography (chloroform). The product was dissolved into 150 ml of a 5% sodium hydroxide-ethanol solution and stirred at room temperature for 8 hours. Then, 95 ml of 2N sulfuric acid was added to obtain a solid. The solid material was filtered and washed with water to obtain 3.1 gm of 18-methyleicosanoic acid (yield: 59% from methyl 18-methyl-16-eicosenoate).
CCC(C)CCCCCCCCCCCCCCCCC(=O)OC
null
[H][H]
CCC(C)C=CCCCCCCCCCCCCCCC(=O)OC
null
[CH3:1][CH:2]([CH2:23][CH3:24])[CH:3]=[CH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20].[H][H]>[Pt]=O.C(O)(=O)C>[CH3:1][CH:2]([CH2:23][CH3:24])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20]
null
CC(=O)O
null
null
null
56.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,231,133
null
null
null
null
ord_dataset-e96f5a2842f14e5380461c234100f05a
2012-01-01T00:12:00
true
Heat 259.8 mg (0.771 mmol) of 4-chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine and 228 mg of 4-(2-aminophenyl)butanoic acid methyl ester (85% strength, approx. 1.0 mmol) to 150° C. overnight. After cooling, concentrate under reduced pressure, add dichloromethane to the residue and purify the crude product by chromatography on silica gel (eluent: dichloromethane/ethyl acetate 50:1→10:1). The product thus obtained is purified further by preparative RP-HPLC. 33.1 mg (8.7% of theory) of the target product are obtained.
COC(=O)CCCc1ccccc1Nc1ncnc2oc(-c3ccccc3)c(-c3ccc(OC)cc3)c12
null
COC(=O)CCCc1ccccc1N
COc1ccc(-c2c(-c3ccccc3)oc3ncnc(Cl)c23)cc1
null
Cl[C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[C:9]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:25][O:26][C:27](=[O:38])[CH2:28][CH2:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[NH2:37]>>[CH3:25][O:26][C:27](=[O:38])[CH2:28][CH2:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[NH:37][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[C:9]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[O:8][C:4]=2[N:5]=[CH:6][N:7]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
271,468
null
null
null
null
ord_dataset-347c0709d28a44dea43ca42052be4db3
1993-01-01T00:07:00
true
To N-(1-benzyl-4-piperidinyl)-2-formyl-3-methylaniline (7.0 g) are added methanol (100 ml) and methyl (triphenylphosphoranylidene)acetate (15 g) and the mixture is refluxed for 1 hour. After cooling, the formed crystals are separated by filtration to give methyl 2-methyl-5-[(1-benzyl-4-piperidinyl)amino]cinnamate (5.6 g) as pale yellow powders, m.p. 140°-142° C.
COC(=O)C=Cc1cc(NC2CCN(Cc3ccccc3)CC2)ccc1C
null
Cc1cccc(NC2CCN(Cc3ccccc3)CC2)c1C=O
COC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
CO
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[C:16]=2C=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(=[CH:43][C:44]([O:46][CH3:47])=[O:45])(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:48]O>>[CH3:48][C:18]1[CH:19]=[CH:20][C:15]([NH:14][CH:11]2[CH2:10][CH2:9][N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:13][CH2:12]2)=[CH:16][C:17]=1[CH:21]=[CH:43][C:44]([O:46][CH3:47])=[O:45]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,667,400
[Cl-]
[Na+]
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
ord_dataset-9cc455db05a444779921f786a45b21a6
2015-01-01T00:12:00
true
1-[3-(1-Azido-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-5-chloro-2-ethoxy-4-fluorophenyl]ethanone (750 mg, 1.8 mmol) (from Step 5) was stirred in tetrahydrofuran (10 mL) with water (0.33 mL) and triphenylphosphine was added. The mixture was heated to 60° C. for 2 hours and cooled to rt. Brine was added and the mixture was extracted with ethyl acetate. The extracts were dried over sodium sulfate, filtered and evaporated to give the desired compound 700 mg, 100%. LCMS calculated for C18H30ClFNO3Si (M+H)+: m/z=390.2; found: 390.2.
CCOc1c(C(C)=O)cc(Cl)c(F)c1C(N)CO[Si](C)(C)C(C)(C)C
null
CCOc1c(C(C)=O)cc(Cl)c(F)c1C(CO[Si](C)(C)C(C)(C)C)N=[N+]=[N-]
null
null
[N:1]([CH:4]([C:14]1[C:15]([O:25][CH2:26][CH3:27])=[C:16]([C:22](=[O:24])[CH3:23])[CH:17]=[C:18]([Cl:21])[C:19]=1[F:20])[CH2:5][O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8])=[N+]=[N-].O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.[Cl-].[Na+].O>[NH2:1][CH:4]([C:14]1[C:15]([O:25][CH2:26][CH3:27])=[C:16]([C:22](=[O:24])[CH3:23])[CH:17]=[C:18]([Cl:21])[C:19]=1[F:20])[CH2:5][O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]
null
O
C1CCOC1
null
60
null
99.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,639,845
Cc1ccc(S(=O)(=O)O)cc1
null
null
null
ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d
2015-01-01T00:09:00
true
A solution of Intermediate 1 (1 g, 3.24 mmol) and 3-amino-4-methylbenzamide (584 mg, 3.89 mmol) in 0.08 M PTSA in 1,4-dioxane was heated to 90° C. for 48 h. TLC showed the completion of starting material (TLC system: 10% methanol/DCM, (Rf): 0.5). The reaction mixture was concentrated, quenched with water, and the precipitated solid was filtered and dried under vacuum. The crude solid was purified by silica gel column chromatography by using 3% methanol/DCM as eluents. The purified solid was further triturated with ether, filtered and dried under vacuum to get the title compound as an off-white solid (430 mg, 31%). 1HNMR (400 MHz, D6-DMSO) δ 2.17 (s, 3H), 5.78-5.81 (dd, 1H J=1.8, 10.1 Hz), 6.28-6.32 (dd, 1H J=1.8, 17 Hz), 6.43-6.50 (dd, 1H J=10.1, 17 Hz), 7.04-7.08 (m, 2H), 7.18-7.24 (m, 2H), 7.27 (br s, 1H), 7.52-7.54 (dd, 1H J=1.7, 7.9 Hz), 7.73-7.76 (m, 1H), 7.87 (br s, 1H), 7.92 (d, 1H), 8.03 (s, 1H), 8.39 (s, 1H), 8.62 (s, 1H), 10.19 (s, 1H). MS m/z: 423.5 (ES+, M+H).
C=CC(=O)Nc1ccccc1Nc1nc(Nc2cc(C(N)=O)ccc2C)ncc1Cl
null
C=CC(=O)Nc1ccccc1Nc1nc(Cl)ncc1Cl
Cc1ccc(C(N)=O)cc1N
null
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[NH:15][C:16](=[O:19])[CH:17]=[CH2:18])[C:5]([Cl:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=1[CH3:31])[C:25]([NH2:27])=[O:26].CO.C(Cl)Cl>CC1C=CC(S(O)(=O)=O)=CC=1.O1CCOCC1>[C:16]([NH:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[NH:8][C:6]1[C:5]([Cl:20])=[CH:4][N:3]=[C:2]([NH:21][C:22]2[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=2[CH3:31])[C:25]([NH2:27])=[O:26])[N:7]=1)(=[O:19])[CH:17]=[CH2:18]
null
CO
ClCCl
C1COCCO1
null
31.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
134,307
[Zn]
null
null
null
ord_dataset-b76b52f4448a4eedb28ffcd8f902046a
1985-01-01T00:09:00
true
Methyl 2-[(4R)-3-bromo-4-allyl-2-oxoazetidin-1-yl]-3-methyl-2-butenoate (840 mg) was dissolved in methylene chloride (6 ml) and cooled to 5° C. To this cooled solution were added acetic acid (0.5 ml) and zinc powder (0.60 g), and the mixture was allowed to warm to room temperature. After stirring for 30 minutes, the reaction mixture was diluted with ethyl acetate (6 ml) and filtered through a pad of Celite. The filtrate was further diluted with ethyl acetate (50 ml) and washed successively with water, dilute sodium bicarbonate and brine. Drying over magnesium sulfate and evaporation left an oil, which was chromatographed on silica gel (20 g) eluting with a mixture of benzene and acetone (5:1) to give methyl 2-[(4R)-4-allyl-2-oxoazetidin-1-yl]-3-methyl-2-butenoate (174 mg) as an oil.
C=CC[C@@H]1CC(=O)N1C(C(=O)OC)=C(C)C
null
C=CC[C@@H]1C(Br)C(=O)N1C(C(=O)OC)=C(C)C
null
null
Br[CH:2]1[C@@H:5]([CH2:6][CH:7]=[CH2:8])[N:4]([C:9](=[C:14]([CH3:16])[CH3:15])[C:10]([O:12][CH3:13])=[O:11])[C:3]1=[O:17].C(O)(=O)C>C(Cl)Cl.C(OCC)(=O)C.[Zn]>[CH2:6]([C@H:5]1[N:4]([C:9](=[C:14]([CH3:16])[CH3:15])[C:10]([O:12][CH3:13])=[O:11])[C:3](=[O:17])[CH2:2]1)[CH:7]=[CH2:8]
0.5
CCOC(C)=O
ClCCl
CC(=O)O
5
28
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
190,264
[Li]CCCC
null
null
null
ord_dataset-be83cbc722064f3696975001242f9f1a
1989-01-01T00:05:00
true
A solution of 1-methoxymethoxy-naphthalene (3.76 g, 0.020 mole) in dry ether (40 mL) was treated with n-butyllithium (1.6M in hexane; 25.0 mL, 0.040 mole) at room temperature over a period of 15 minutes. After stirring for an additional 1.5 hours, a solution of cyclohexanone (4.90 g, 0.050 mole) in ether (15 mL) was added and the resulting mixture was stirred at room temperature for 2 hours. It was then quenched with saturated aqueous ammonium chloride and the crude product was isolated by extraction with ether. Chromatography with 9:1 hexane/ethyl acetate provided the title compound as a colorless oil (3.30 g, 58%).
COCOc1c(C2(O)CCCCC2)ccc2ccccc12
null
O=C1CCCCC1
COCOc1cccc2ccccc12
null
[CH3:1][O:2][CH2:3][O:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][CH:6]=1.C([Li])CCC.[C:20]1(=[O:26])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.CCCCCC.C(OCC)(=O)C>CCOCC>[OH:26][C:20]1([C:6]2[CH:7]=[CH:8][C:9]3[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:5]=2[O:4][CH2:3][O:2][CH3:1])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1
1.5
CCOCC
CCCCCC
CCOC(C)=O
null
null
57.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
686,856
null
null
null
null
ord_dataset-56747de2718a4ac5bf061651d1cc9e3e
2005-01-01T00:10:00
true
To a stirred solution of the 2-methyl-5-(2-pyrrolidine-1-yl-ethylamino)-1H-indole-3-carboxylic acid benzyl ester (147 mg, 0.39 mmol, 1.0 eq) and triethylamine (47.6 mg, 0.47 mmol, 1.2 eq) in acetonitrile in an ice-water bath was added dropwise a solution of acetyl chloride in acetonitrile. After the ice-water bath was removed, the reaction mixture was heated to reflux for overnight. After the mixture was concentrated, the residue was purified by preparative HPLC (reverse-phase, 10-100 CH3CN:H2O, 0.1% TFA) to yield the desire indole amine in 33.0% yield. Elemental Analysis: C25H29N3O3.2HCl.0.3H2O Calcd: C: 60.31; H: 6.40; N: 8.44. Found: C: 60.63; H: 6.40; N: 8.04. ESI-MS: m/z 420.78 (M+H)+.
Nc1cc2ccccc2[nH]1
null
Cc1[nH]c2ccc(NCCN3CCCC3)cc2c1C(=O)OCc1ccccc1
CCN(CC)CC
null
C(OC([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17](NCCN3CCCC3)[CH:18]=2)[NH:13][C:12]=1C)=O)C1C=CC=CC=1.C([N:31](CC)CC)C.C(Cl)(=O)C>C(#N)C>[NH:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]=[C:12]1[NH2:31]
null
CC(=O)Cl
CC#N
null
null
null
33
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
671,962
CCN=C=NCCCN(C)C
Cl
On1nnc2ccccc21
null
ord_dataset-e90cd41afe844e49875435eb99903799
2005-01-01T00:05:00
true
A solution (2R)-2-(4,4-dimethyl-2-oxopentyl)-4-pentenoic acid (Preparation 112) (15.91 g, 74.3 mmol), 1-hydroxybenzotriazole hydrate (11.00 g, 81.4 mmol), L-serine ethylester hydrochloride (13.84 g, 81.6 mmol) and N,N-diisopropylethylamine (27 ml, 156.0 mmol) in dichloromethane (280 ml) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (15.67 g, 81.7 mmol) and stirred at room temperature for 18 hours under a nitrogen atmosphere. The reaction mixture was diluted with dichloromethane and washed with water, aqueous citric acid (2M), saturated sodium hydrogen carbonate solution and brine, dried over anhydrous sodium sulphate and filtered. The solvent was removed under reduced pressure to afford the title compound as a yellow oil (23.8 g).
C=CC[C@H](CC(=O)CC(C)(C)C)C(=O)N[C@@H](CO)C(=O)OCC
null
C=CC[C@H](CC(=O)CC(C)(C)C)C(=O)O
CCOC(=O)[C@@H](N)CO
null
[CH3:1][C:2]([CH3:15])([CH3:14])[CH2:3][C:4](=[O:13])[CH2:5][C@@H:6]([CH2:10][CH:11]=[CH2:12])[C:7]([OH:9])=O.O.ON1C2C=CC=CC=2N=N1.Cl.[CH2:28]([O:30][C:31](=[O:36])[C@H:32]([CH2:34][OH:35])[NH2:33])[CH3:29].C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>ClCCl>[CH3:14][C:2]([CH3:1])([CH3:15])[CH2:3][C:4](=[O:13])[CH2:5][C@@H:6]([CH2:10][CH:11]=[CH2:12])[C:7]([NH:33][C@@H:32]([CH2:34][OH:35])[C:31]([O:30][CH2:28][CH3:29])=[O:36])=[O:9]
18
CCN(C(C)C)C(C)C
O
ClCCl
25
97.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,532,078
null
null
null
null
ord_dataset-8d5c200bca27407ab9febe7598e16458
2015-01-01T00:01:00
true
The title compound was prepared according to Method 4 using (4S,5R)-3-(tert-butoxycarbonyl)-5-isopropyl-2,2-dimethyl-1,3-oxazolidine-4-carboxylic acid (Preparation 60) and 4-(1-methylethyl)-1,2-benzenediamine.
CC(C)c1ccc2[nH]c([C@@H](N)[C@H](O)C(C)C)nc2c1
null
CC(C)[C@H]1OC(C)(C)N(C(=O)OC(C)(C)C)[C@@H]1C(=O)O
CC(C)c1ccc(N)c(N)c1
null
C(OC([N:8]1[C@H:12]([C:13](O)=O)[C@@H:11]([CH:16]([CH3:18])[CH3:17])[O:10]C1(C)C)=O)(C)(C)C.[CH3:21][CH:22]([C:24]1[CH:25]=[C:26]([NH2:31])[C:27]([NH2:30])=[CH:28][CH:29]=1)[CH3:23]>>[NH2:8][C@H:12]([C:13]1[NH:30][C:27]2[CH:28]=[CH:29][C:24]([CH:22]([CH3:21])[CH3:23])=[CH:25][C:26]=2[N:31]=1)[C@H:11]([OH:10])[CH:16]([CH3:18])[CH3:17]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,701,529
O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
null
null
null
ord_dataset-54347fcace774f89850681d6dec8009f
2016-01-01T00:03:00
true
A solution of 47.9 g (161 mmol) of (2S,5S)-tert-butyl 5-hydroxy-1-(2,2,2-trifluoroacetyl)piperidine-2-carboxylate in dehydrated acetonitrile (318 mL) was cooled from −30 to −40° C. under argon atmosphere, and 20.5 mL (177 mmol) of 2,6-lutidine was added, and then 28.4 mL (169 mmol) of trifluoromethanesulfonic acid anhydride was added dropwise over 40 minutes, followed by further allowing to react at −30° C. for 15 minutes. To this reaction mixture was added 39.7 g (322 mmol) of benzyloxyamine (washed with acetonitrile (11 mL)) within 8 minutes, followed by raising the temperature to 0° C. within 30 minutes, and further 20.5 mL (177 mmol) of 2,6-lutidine was added, followed by allowing to react at 0 to 5° C. for 2 days. This reaction mixture was concentrated under reduced pressure, and the resulting residue was diluted with ethyl acetate (960 mL) and washed sequentially with water (960 mL), 10% aqueous citric acid solution (960 mL×3 times), 6.5% aqueous sodium hydrogencarbonate solution (480 mL) and saturated brine (480 mL). Each aqueous layer was back-extracted with ethyl acetate (960 mL), the organic layers were combined, and the solvent was distilled off under reduced pressure. The resulting residue was dissolved in 1,4-dioxane (320 mL) solution and water (86 mL), and, under ice cooling, 2.5M NaOH (128 mL) was added dropwise, followed by allowing to react at the same temperature for 0.5 hours. Acetic acid (ca. 9.3 mL) was added to the reaction mixture, followed by concentration under reduced pressure, and subsequently the resulting concentrated residue was extracted with ethyl acetate (580 mL, 290 mL). After the organic layers were washed respectively with 50% aqueous potassium carbonate solution (580 mL), they were combined, and the solvent was distilled off under reduced pressure. The resulting residue was applied to silica gel column chromatography (hexane/ethyl acetate=4/1→0/1→ethyl acetate/methanol=100/1→19/1) to afford 36.58 g of the title compound as a colorless oil (yield 74%). Instrumental data were consistent with those of Example 4.
CC(C)(C)OC(=O)[C@@H]1CC[C@@H](NOCc2ccccc2)CN1
null
NOCc1ccccc1
CC(C)(C)OC(=O)[C@@H]1CC[C@H](O)CN1C(=O)C(F)(F)F
null
O[C@@H:2]1[CH2:7][N:6](C(=O)C(F)(F)F)[C@H:5]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:4][CH2:3]1.N1C(C)=CC=CC=1C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[CH2:44]([O:51][NH2:52])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>C(#N)C.C(O)(=O)C>[CH2:44]([O:51][NH:52][C@H:2]1[CH2:7][NH:6][C@H:5]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:4][CH2:3]1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1
null
Cc1cccc(C)n1
CC#N
CC(=O)O
0
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
896,996
null
null
null
null
ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded
2009-01-01T00:08:00
true
Similar procedure as described in example 384 was used, starting from 1-Isopropoxy-3-(5-methyl-1H-pyrazol-3-ylamino)-isoquinoline-6-carboxylic acid and Methyl-(2-piperidin-1-yl-ethyl)-amine to give 1-Isopropoxy-3-(5-methyl-1H-pyrazol-3-ylamino)-isoquinoline-6-carboxylic acid methyl-(2-piperidin-1-yl-ethyl)-amide. LC-MS: m/e 451 (MH+).
Cc1cc(Nc2cc3cc(C(=O)N(C)CCN4CCCCC4)ccc3c(OC(C)C)n2)n[nH]1
null
CNCCN1CCCCC1
Cc1cc(Nc2cc3cc(C(=O)O)ccc3c(OC(C)C)n2)n[nH]1
null
[CH:1]([O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([C:15]([OH:17])=O)=[CH:12][CH:13]=2)[CH:8]=[C:7]([NH:18][C:19]2[CH:23]=[C:22]([CH3:24])[NH:21][N:20]=2)[N:6]=1)([CH3:3])[CH3:2].[CH3:25][NH:26][CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1>>[CH3:25][N:26]([CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)[C:15]([C:11]1[CH:10]=[C:9]2[C:14](=[CH:13][CH:12]=1)[C:5]([O:4][CH:1]([CH3:2])[CH3:3])=[N:6][C:7]([NH:18][C:19]1[CH:23]=[C:22]([CH3:24])[NH:21][N:20]=1)=[CH:8]2)=[O:17]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
120,637
Cl
null
null
null
ord_dataset-1d493fcbd5494078b46e816998dcb991
1984-01-01T00:08:00
true
In 100 ml of ethanol was dissolved 10.0 g. (0.05 mole) of sodium 2,4-dichloro-3-methylphenolate. With stirring at room temperature, 9.1 g (0.05 mole) of ethyl 2-bromopropionate was added. The mixture was heated under relfux for 4 hours. The ethanol was distilled off under reduced pressure, and the residue was extracted with 50 ml of diethyl ether. The ethereal layer was washed with 25 ml of a 5% aqueous solution of sodium hydroxide and 25 ml of water, and dried over anyhdrous magnesium sulfate. The dessicant was removed by filtration, and the diethyl ether was distilled off to give 11.8 g of crude ethyl 2-(2,4-dichloro-3-methylphenoxy)propionate. The crude ester (11.8 g) was dissolved in 100 ml of glacial acetic acid. Concentrated hydrochloric acid (25 ml) was added, and the mixture was stirred at 100° C. for 40 minutes. The reaction mixture was cooled, and poured onto 300 ml of ice water. The precipitated crystals were filtered, washed with water, and dried to give 9.2 g of 2-(2,4-dichloro-3-methylphenoxy)-propionic acid. The yield was 73.9% based on the sodium 2,4-dichloro-3-methylphenolate, and the final product had a melting point of 149.5 to 150.5° C.
Cc1c(Cl)ccc(OC(C)C(=O)O)c1Cl
null
CCOC(=O)C(C)Oc1ccc(Cl)c(C)c1Cl
null
null
[Cl:1][C:2]1[C:15]([CH3:16])=[C:14]([Cl:17])[CH:13]=[CH:12][C:3]=1[O:4][CH:5]([CH3:11])[C:6]([O:8]CC)=[O:7].Cl>C(O)(=O)C>[Cl:1][C:2]1[C:15]([CH3:16])=[C:14]([Cl:17])[CH:13]=[CH:12][C:3]=1[O:4][CH:5]([CH3:11])[C:6]([OH:8])=[O:7]
0.67
CC(=O)O
null
null
100
86.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
214,827
null
null
null
null
ord_dataset-5ebf3d05077a4f7fb91a1cd9bdc504d2
1990-01-01T00:09:00
true
7-Methylsulfonylamino-3-methylthio-6-phenoxy-4H-1-benzopyran-4-one was reacted with m-chloroperbenzoic acid in equimolar amounts to obtain 3-methylsulfinyl-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one [Compound No. 5].
CS(=O)c1coc2cc(NS(C)(=O)=O)c(Oc3ccccc3)cc2c1=O
null
CSc1coc2cc(NS(C)(=O)=O)c(Oc3ccccc3)cc2c1=O
O=C(OO)c1cccc(Cl)c1
null
[CH3:1][S:2]([NH:5][C:6]1[C:18]([O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:17][C:9]2[C:10](=[O:16])[C:11]([S:14][CH3:15])=[CH:12][O:13][C:8]=2[CH:7]=1)(=[O:4])=[O:3].ClC1C=CC=C(C(OO)=[O:34])C=1>>[CH3:15][S:14]([C:11]1[C:10](=[O:16])[C:9]2[CH:17]=[C:18]([O:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:6]([NH:5][S:2]([CH3:1])(=[O:3])=[O:4])=[CH:7][C:8]=2[O:13][CH:12]=1)=[O:34]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
472,177
[Fe]
null
null
null
ord_dataset-cd531114850e4f239b2a3661044ae672
2000-01-01T00:08:00
true
The product of Example 11 (778 mg), methanol (40.5 mL), acetic acid (13.5 mL) and iron powder (382 mg) were heated at reflux and stirred mechanically for 6 h. More iron powder (1.15 g) was added and the reaction was heated at reflux 2 more hours, after which it was cooled, filtered through celite, and concentrated to a thick black oil. Added ethyl acetate (200 mL) and water (100 mL), stirred, and filtered through celite. The layers were separated and the ethyl acetate dried over MgSO4 and concentrated to a thick yellow oil (754 mg). The oil was chromatographed on silica gel using ethyl acetate/hexane (1:9) as eluent. The title compound was obtained as an off-white solid (526 mg). CI-HRMS calc'd. for C22H26N4Br (M+H)+ : 425.134083. Found: 425.131850.
CCN(c1nc(C)cc(-c2ccccc2N)n1)c1ccc(C(C)C)cc1Br
null
CCN(c1nc(C)cc(-c2ccccc2[N+](=O)[O-])n1)c1ccc(C(C)C)cc1Br
null
null
[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:28][CH3:29])[C:12]1[N:17]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[N+:24]([O-])=O)[CH:15]=[C:14]([CH3:27])[N:13]=1.CO>[Fe].C(O)(=O)C>[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:28][CH3:29])[C:12]1[N:17]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[NH2:24])[CH:15]=[C:14]([CH3:27])[N:13]=1
6
CC(=O)O
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
491,712
[K+]
null
null
null
ord_dataset-37b0416f244344a08cf357e851eedf2a
2001-01-01T00:01:00
true
Potassium thioacetate (0.22 g) is added to a solution of 1.07 g of (3R,5S)-1-allyloxycarbonyl-3-methane sulfonyloxy-5-[2-(imidazo[5,1-b]thiazol-2-yl)vinyl]pyrrolidine (a mixture of geometrical isomers) in 5 ml of DMF, and the mixture is stirred at 70° C. for 4 hr. Ethyl acetate is added to the reaction mixture, and the mixture is successively washed with water and a saturated aqueous sodium hydrogencarbonate solution, and saturated saline and dried over magnesium sulfate. The solvent is removed by evaporation. The residue is purified by column chromatography on silica gel to give 0.42 g of the title compound.
C=CCOC(=O)N1C[C@@H](SC(C)=O)C[C@H]1C=Cc1cn2cncc2s1
null
CC([O-])=S
C=CCOC(=O)N1C[C@H](OS(C)(=O)=O)C[C@H]1C=Cc1cn2cncc2s1
null
[C:1]([O-:4])(=[S:3])[CH3:2].[K+].[CH2:6]([O:9][C:10]([N:12]1[C@H:16]([CH:17]=[CH:18][C:19]2[S:23][C:22]3=[CH:24][N:25]=[CH:26][N:21]3[CH:20]=2)[CH2:15][C@@H:14](OS(C)(=O)=O)[CH2:13]1)=[O:11])[CH:7]=[CH2:8].C(OCC)(=O)C>CN(C=O)C>[C:1]([S:3][C@H:14]1[CH2:15][C@@H:16]([CH:17]=[CH:18][C:19]2[S:23][C:22]3=[CH:24][N:25]=[CH:26][N:21]3[CH:20]=2)[N:12]([C:10]([O:9][CH2:6][CH:7]=[CH2:8])=[O:11])[CH2:13]1)(=[O:4])[CH3:2]
4
CN(C)C=O
CCOC(C)=O
null
70
null
57.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
938,457
null
null
null
null
ord_dataset-90b0aa1f83334a02919b2be3a1c04542
2010-01-01T00:02:00
true
Prepared by the method of Example 31 using 2,6-bis(hydroxymethyl)pyridine (0.11 g) and 2,3-dichloro-N-(3,5-dichloro-2-pyrazinyl)benzenesulphonamide (Example 74) (0.11 g) in N-methylpyrrolidinone (2 mL). Yield 0.043 g.
O=S(=O)(Nc1ncc(Cl)nc1OCc1cccc(CO)n1)c1cccc(Cl)c1Cl
null
O=S(=O)(Nc1ncc(Cl)nc1Cl)c1cccc(Cl)c1Cl
OCc1cccc(CO)n1
null
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][OH:10])[N:4]=1.[Cl:11][C:12]1[C:17]([Cl:18])=[CH:16][CH:15]=[CH:14][C:13]=1[S:19]([NH:22][C:23]1[C:28](Cl)=[N:27][C:26]([Cl:30])=[CH:25][N:24]=1)(=[O:21])=[O:20]>CN1CCCC1=O>[Cl:11][C:12]1[C:17]([Cl:18])=[CH:16][CH:15]=[CH:14][C:13]=1[S:19]([NH:22][C:23]1[C:28]([O:1][CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][OH:10])[N:4]=2)=[N:27][C:26]([Cl:30])=[CH:25][N:24]=1)(=[O:21])=[O:20]
null
CN1CCCC1=O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,264,989
[Na+]
[OH-]
null
null
ord_dataset-d3580a12b15e46cc91aa73f4f1a4a8cc
2013-01-01T00:03:00
true
To a solution of ethyl (4-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)acetate (D145) (80 mg, 0.148 mmol) in Isopropanol (6 mL) and Water (6.00 mL) was added NaOH (1.476 mL, 0.738 mmol). The reaction solution was heated to 90° C. for 2 hours. The solvent was removed in vacuo and the residue was acidified to pH=3-4, extracted with ethyl acetate. The combined organic phases were dried, concentrated and purified by Mass Directed AutoPrep to afford (4-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-1-piperidinyl)acetic acid (E105) (59 mg) as a TFA salt. δH (DMSO-d6, 400 MHz): 1.01 (3H, t), 1.28 (6H, d), 1.55 (2H, m), 1.72 (3H, m), 2.62 (2H, d), 2.87 (4H, m), 3.38 (2H, m), 3.98 (2H, s), 4.79 (1H, m), 7.23 (2H, m), 7.32 (1H, d), 7.59 (1H, dd), 7.95 (1H, dd), 8.07 (1H, d). δF (DMSO-d6, 376 MHz): −73.5. MS (ES): C27H32ClN3O3S requires 513.2. found 514.2 (M+H+).
CCc1c(CC2CCN(CC(=O)O)CC2)cccc1-c1nsc(-c2ccc(OC(C)C)c(Cl)c2)n1
null
CCOC(=O)CN1CCC(Cc2cccc(-c3nsc(-c4ccc(OC(C)C)c(Cl)c4)n3)c2CC)CC1
null
null
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][N:15]=[C:14]([C:17]3[C:18]([CH2:36][CH3:37])=[C:19]([CH2:23][CH:24]4[CH2:29][CH2:28][N:27]([CH2:30][C:31]([O:33]CC)=[O:32])[CH2:26][CH2:25]4)[CH:20]=[CH:21][CH:22]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>C(O)(C)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][N:15]=[C:14]([C:17]3[C:18]([CH2:36][CH3:37])=[C:19]([CH2:23][CH:24]4[CH2:25][CH2:26][N:27]([CH2:30][C:31]([OH:33])=[O:32])[CH2:28][CH2:29]4)[CH:20]=[CH:21][CH:22]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]
null
O
CC(C)O
null
90
77.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,519,951
[H-]
[Na+]
null
null
ord_dataset-8c74302143c04eb9983e4b3a7ead2d72
2014-01-01T00:12:00
true
1-Cyclobutyl-piperidin-4-ol (0.04 grams, 0.26 mmol) in tetrahydrofuran (3 mL) was treated with cooled and stirred suspension of sodium hydride (0.021 grams, 0.51 mmol) in tetrahydrofuran (8 mL) slowly over the period of 5 minutes and the reaction mixture was stirred for 2 hours at room temperature. A solution of (2-Bromo-4,5,7,8-tetrahydro-thiazolo[5,4-d]azepin-6-yl)-cyclopropyl-methanone (0.053 grams, 0.17 mmol, obtained in above step) in tetrahydrofuran (3 mL) was added drop wise over a period of 5 minutes and refluxed for 15 hours. Reaction mass was quenched onto ice cold water and the product was extracted with ethyl acetate (3×10 mL). The combined organics were washed with water followed by brine and dried over anhydrous sodium sulphate. Organic volatiles were evaporated under vacuum. The residue obtained was purified by flash chromatography (methanol/chloroform 3/97) to obtain the title compound (0.05 grams).
O=C(C1CC1)N1CCc2nc(OC3(C4CCC4)CCNCC3)sc2CC1
null
OC1CCN(C2CCC2)CC1
O=C(C1CC1)N1CCc2nc(Br)sc2CC1
C1CCOC1
C1([N:5]2[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]2)CCC1.[H-].[Na+].Br[C:15]1[S:16][C:17]2[CH2:18][CH2:19][N:20]([C:25]([CH:27]3[CH2:29][CH2:28]3)=[O:26])[CH2:21][CH2:22][C:23]=2[N:24]=1.O1[CH2:34][CH2:33][CH2:32][CH2:31]1>>[CH:31]1([C:8]2([O:11][C:15]3[S:16][C:17]4[CH2:18][CH2:19][N:20]([C:25]([CH:27]5[CH2:29][CH2:28]5)=[O:26])[CH2:21][CH2:22][C:23]=4[N:24]=3)[CH2:7][CH2:6][NH:5][CH2:10][CH2:9]2)[CH2:34][CH2:33][CH2:32]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
708,780
NN
null
null
null
ord_dataset-c8069773c1a148aca8ab417108daacc5
2006-01-01T00:05:00
true
To a solution of 4-iodo-3-nitroanisole (5 g, 17.9 mmole) in 100 ml methanol was added FeCl3 (50 mg, 0.3 mmole) and activated carbon (40 mg). The mixture was heated to reflux and hydrazine hydrate (1.75 g, 35 mmole) was added dropwise. The mixture was refluxed for an additional 8 hours and cooled to room temperature, filtered through Celite. The filtrate was concentrated and purified by column chromatography (eluting with 10% EtOAc in hexanes) to give 4.05 g product as pale yellow oil (91% yield). 1H NMR (300 MHz, CDCl3) δ 7.47 (1H, d, J=8.7 Hz), 6.31 (1H, d, J=2.8 Hz), 6.13 (1H, dd, J=2.8, 8.7 Hz), 3.73 (3H, s).
COc1ccc(I)c(N)c1
null
COc1ccc(I)c([N+](=O)[O-])c1
null
null
[I:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[N+:10]([O-])=O.O.NN>CO>[I:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[NH2:10]
null
O
CO
null
25
null
90.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
398,577
[Pd+2]
CC(=O)[O-]
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
ord_dataset-a4a191e812a64d0598ea918f047e8da7
1998-01-01T00:04:00
true
A solution of allyl acetate (13.5 ml, 125 mmol) in THF (8 ml), was evacuated and purged with argon (3 times). Palladium acetate (122 mg, 0.50mmol) and triphenylphosphine (525 mg, 2.0 mmol) were added as solutions in tetrahydrofuran (1.5 ml each), followed by 3-nitro-6-trifluoromethyl-2-pyridinone (2.6 g, 12.5 mmol) in THF (2 ml). The reaction was heated to reflux for 64 h, and more allyl acetate (13.5 ml, 125 mmol), triphenylphosphine (525 mg, 2.0 mmol), palladium acetate (122 mg, 0.5 mmol), and tetrahydrofuran (13 ml) were added. After a further 24 h and 48 h at reflux addditional allyl acetate (13.5 ml, 125 mmol), palladium acetate (122 mg, 0.5 mmol), and triphenylphosphine (525 mg, 2.0 mmol) were added and the reaction was heated to reflux for a further 24 h. The reaction was cooled and evaported in vacuo to a gum which was purified by flash column chromatography on silica (15% ethyl acetate/hexane) to give the product contaminated with unreacted 3-nitro-6-trifluoromethyl-2-pyridinone. This material was diluted with ethyl acetate and washed with water adjusted to pH 12 with sodium carbonate, dried (Na2SO4), and evaporated in vacuo to give the title compound (1.05 g): 1H NMR (CDCl3) selected signals at δ4.80 (d, J=5.8 Hz, 2H), 5.28-5.33 (m, 2H), 5.86-5.96 (m, 1H), 6.80 (d, J=7.9 Hz, 1H), 8.22 (d, J=7.9 Hz, 1H).
C=CCn1c(C(F)(F)F)ccc([N+](=O)[O-])c1=O
null
O=c1[nH]c(C(F)(F)F)ccc1[N+](=O)[O-]
C=CCOC(C)=O
null
C(O[CH2:5][CH:6]=[CH2:7])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+:27]([C:30]1[C:31](=[O:40])[NH:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=1)([O-:29])=[O:28]>C1COCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N+:27]([C:30]1[C:31](=[O:40])[N:32]([CH2:7][CH:6]=[CH2:5])[C:33]([C:36]([F:39])([F:37])[F:38])=[CH:34][CH:35]=1)([O-:29])=[O:28]
24
C1CCOC1
CCOC(C)=O
null
null
33.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,512,380
Cl
null
null
null
ord_dataset-1a1aa5d1c3224edca0aec6e3398da985
2014-01-01T00:11:00
true
To a solution of (S)-methyl 5-(tert-butyldimethylsilyloxy)-4-(3-(2,3-difluorobenzyl)-1-methylureido)pentanoate (9.7 g, 21.6 mmol) in MeOH (40 mL) was added HCl (4 N in dioxane, 5.4.0 mL, 21.6 mmol). The resulting solution was stirred at RT for 1 h. The mixture was concentrated and re-dissolved in EtOAc. The organic mixture was washed with saturated NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to give (S)-methyl 4-(3-(2,3-difluorobenzyl)-1-methylureido)pentanoate (6.84 g, crude) as a white solid, which was used without further purification. LRMS (M+H+) m/z 331.2.
COC(=O)CC[C@H](C)N(C)C(=O)NCc1cccc(F)c1F
null
COC(=O)CC[C@@H](CO[Si](C)(C)C(C)(C)C)N(C)C(=O)NCc1cccc(F)c1F
null
null
[Si](O[CH2:9][C@@H:10]([N:17]([CH3:30])[C:18]([NH:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:23]=1[F:29])=[O:19])[CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])(C(C)(C)C)(C)C.Cl>CO>[F:29][C:23]1[C:24]([F:28])=[CH:25][CH:26]=[CH:27][C:22]=1[CH2:21][NH:20][C:18](=[O:19])[N:17]([C@@H:10]([CH3:9])[CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])[CH3:30]
1
CO
null
null
25
null
100.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
221,327
null
null
null
null
ord_dataset-42629b4cf1094978a5e5f29f22639ee7
1991-01-01T00:01:00
true
Methyl [1-(3-propylphenyl)hydrazino]acetate (700 mg) was dissolved in acetonitrile (10 ml) under nitrogen at room temperature. Methyl isocyanate (0.69 ml) was added to the solution which was then heated at 80° for 85 min. The solvent was removed in vacuo and the residue was dissolved in ether (10 ml). Hexane (20 ml) was added to precipitate a solid which was filtered off to give the title compound (677 mg), m.p. 76°-77°.
CCCc1cccc(N(CC(=O)OC)NC(=O)NC)c1
null
CCCc1cccc(N(N)CC(=O)OC)c1
CN=C=O
null
[CH2:1]([C:4]1[CH:5]=[C:6]([N:10]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[NH2:11])[CH:7]=[CH:8][CH:9]=1)[CH2:2][CH3:3].[CH3:17][N:18]=[C:19]=[O:20]>C(#N)C>[CH3:17][NH:18][C:19]([NH:11][N:10]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([CH2:1][CH2:2][CH3:3])[CH:5]=1)=[O:20]
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
588,128
Cl
null
null
null
ord_dataset-7a74d48eeefd45aba53e7258f3ae067a
2003-01-01T00:04:00
true
The 4,6-dichloro-pyrido[3,4-d]pyrimidine obtained from the previous reaction was taken up in dioxane (50 ml), the 3-methyl 4-phenoxy aniline hydrochloride (2.8 g, 12 mmol) was added and the contents heated to an external bath temperature of −80° C. for 3 hours, whereupon yellow precipitation occurred. Further dioxane (20 ml) was added and the contents heated at −75° C. for 12 hours. The solution was then filtered and the yellow solid placed under vacuum to provide the desired (6-chloro-pyrido[3,4-d]pyrimidin-4-yl)-(3-methyl-4-phenoxy-phenyl)-amine hydrochloride (3.6 g, ˜100%). 1H NMR (CD3OD; 400 MHz) δ 9.05 (s, 1H), 8.87 (s, 1H), 8.64 (s, 1H), 7.69 (d, J=2.5 Hz, 1H), 7.58 (dd, J=8.7, 2.5 Hz, 1H),7.35 (dd, J=8.7, 7.5 Hz, 2H), 7.10 (t, J=7.2 Hz, 1H), 6.94 (d, J=8.7 Hz, 3H), 2.29 (s, 3H). MS m/z (MH+): 363.2
Cc1cc(Nc2ncnc3cnc(Cl)cc23)ccc1Oc1ccccc1
null
Cc1cc(N)ccc1Oc1ccccc1
Clc1cc2c(Cl)ncnc2cn1
null
[Cl:1][C:2]1[C:3]2[CH:11]=[C:10]([Cl:12])[N:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.Cl.[CH3:14][C:15]1[CH:16]=[C:17]([CH:19]=[CH:20][C:21]=1[O:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[NH2:18]>O1CCOCC1>[ClH:1].[Cl:12][C:10]1[N:9]=[CH:8][C:4]2[N:5]=[CH:6][N:7]=[C:2]([NH:18][C:17]3[CH:19]=[CH:20][C:21]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[C:15]([CH3:14])[CH:16]=3)[C:3]=2[CH:11]=1
null
C1COCCO1
null
null
-80
100
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,475,346
null
null
null
null
ord_dataset-c3c1091f873b4f40827973a6f1f9b685
2014-01-01T00:09:00
true
The title compound was prepared in analogy to the synthesis of compound of Example 2, using tert-butyl 4-(4-(4,4,5-trimethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate and with an additional deprotection step before final reduction (tR 1.0 min (conditions 1), MH+=410).
c1cnc2ccc(Cc3cnc4ccc(-c5cnn(C6CCNCC6)c5)nn34)cc2c1
null
CC1OB(c2cnn(C3CCN(C(=O)OC(C)(C)C)CC3)c2)OC1(C)C
Cn1cc(-c2ccc3ncc(Cc4ccc5ncccc5c4)n3n2)cn1
null
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([CH2:16][C:17]4[CH:18]=[C:19]5[C:24](=[CH:25][CH:26]=4)[N:23]=[CH:22][CH:21]=[CH:20]5)=[CH:14][N:15]=3)[N:12]=2)[CH:4]=[N:3]1.CC1(C)C(C)OB([C:34]2C=N[N:37]([CH:39]3CCN(C(OC(C)(C)C)=O)C[CH2:40]3)[CH:38]=2)O1>>[NH:37]1[CH2:39][CH2:40][CH:1]([N:2]2[CH:6]=[C:5]([C:7]3[CH:8]=[CH:9][C:10]4[N:11]([C:13]([CH2:16][C:17]5[CH:18]=[C:19]6[C:24](=[CH:25][CH:26]=5)[N:23]=[CH:22][CH:21]=[CH:20]6)=[CH:14][N:15]=4)[N:12]=3)[CH:4]=[N:3]2)[CH2:34][CH2:38]1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,527,569
[Al+3]
[Cl-]
null
null
ord_dataset-8c74302143c04eb9983e4b3a7ead2d72
2014-01-01T00:12:00
true
To a solution of 5-bromo-2-chloro-4-methoxybenzoic acid (4, 15 g, 56.5 mmol) in toluene (72 mL) was added thionyl chloride (8.24 mL, 113 mmol) and N,N-dimethylformamide (0.1 mL). The solution was refluxed at 90° C. for 4 h, cooled to room temperature and evaporated to remove toluene and residual reagent. The obtained acyl chloride was diluted with dichloromethane (240 mL) and added portionwise aluminum chloride (8.3 g, 62.2 mmol) and phenetole (7.2 mL, 56.5 mmol) at 0° C. The reaction mixture was stirred at room temperature overnight, quenched with 1N HCl (15 mL) and H2O (15 mL). The organic layer was extracted with dichloromethane two times, washed with 1N HCl and brine, dried over magnesium sulfate, filtered and concentrated in vacuo to yield the title compound as a yellowish solid which was used without further purification.
CCOc1ccc(C(=O)c2cc(Br)c(OC)cc2Cl)cc1
null
COc1cc(Cl)c(C(=O)O)cc1Br
CCOc1ccccc1
null
[Br:1][C:2]1[C:3]([O:12][CH3:13])=[CH:4][C:5]([Cl:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.S(Cl)(Cl)=O.[Cl-].[Al+3].[Cl-].[Cl-].[C:22]1([O:28][CH2:29][CH3:30])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1(C)C=CC=CC=1.CN(C)C=O>[Br:1][C:2]1[C:3]([O:12][CH3:13])=[CH:4][C:5]([Cl:11])=[C:6]([C:7]([C:25]2[CH:26]=[CH:27][C:22]([O:28][CH2:29][CH3:30])=[CH:23][CH:24]=2)=[O:9])[CH:10]=1
8
Cc1ccccc1
CN(C)C=O
O=S(Cl)Cl
90
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,495,010
[Pd+2]
[OH-]
null
null
ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2
2014-01-01T00:10:00
true
A suspension of ethyl {4-[2-tert-butyl-4-(1-methylethenyl)phenyl]piperazin-1-yl}(oxo)acetate (Example 166, 0.17 g, 0.474 mmol) and palladium hydroxide (20% on carbon, wetted with ca. 50% water, 20 mg) in ethyl acetate (3 mL) was stirred under hydrogen at room temperature for 30 minutes. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to provide ethyl {4-[2-tert-butyl-4-(1-methylethyl)phenyl]piperazin-1-yl}(oxo)acetate (0.133 g, 78%) as a colorless oil.
CCOC(=O)C(=O)N1CCN(c2ccc(C(C)C)cc2C(C)(C)C)CC1
null
C=C(C)c1ccc(N2CCN(C(=O)C(=O)OCC)CC2)c(C(C)(C)C)c1
null
null
[C:1]([C:5]1[CH:10]=[C:9]([C:11]([CH3:13])=[CH2:12])[CH:8]=[CH:7][C:6]=1[N:14]1[CH2:19][CH2:18][N:17]([C:20](=[O:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:16][CH2:15]1)([CH3:4])([CH3:3])[CH3:2]>C(OCC)(=O)C.[OH-].[Pd+2].[OH-]>[C:1]([C:5]1[CH:10]=[C:9]([CH:11]([CH3:13])[CH3:12])[CH:8]=[CH:7][C:6]=1[N:14]1[CH2:19][CH2:18][N:17]([C:20](=[O:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:16][CH2:15]1)([CH3:3])([CH3:4])[CH3:2]
0.5
CCOC(C)=O
null
null
25
77.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
426,946
CCC(=O)CC(=O)[O-]
[Al+3]
null
null
ord_dataset-1ecf96d88f254270bff816ee7eeffef6
1999-01-01T00:02:00
true
A mixture of 5.3 g of the aluminum tri(methyl acetylacetate) catalyst mentioned in Example 1 and 85 g of 1,2-propylene carbonate was heated to 170° C. and, at this temperature a mixture of 55 g (0.47 mol) of methyl acetoacetate and 43.7 g (0.52 mol) of 2-methyl-3-butyn-2-ol was metered in at a constant rate over the course of 4 h. After the addition was complete, the mixture was stirred at 170° C. for 30 min. During this time, CO2 was evolved and low boilers distilled out. The reaction mixture was subsequently cooled, and the 2-methyl-2,4-heptadien-6-one which was formed was distilled out under about 100 mbar. This resulted in 42 g of pure 2-methyl-2,4-heptadien-6-one, which corresponds to a yield of 72% of theory based on reacted 2-methyl-3-butyn-2-ol.
CC(=O)C=CC=C(C)C
null
O=C=O
COC(=O)CC(C)=O
C#CC(C)(C)O
[C:1]([O:7]C)(=O)[CH2:2][C:3]([CH3:5])=O.[CH3:9][C:10](O)(C#C)[CH3:11].[C:15](=O)=O>CCC(CC([O-])=O)=O.CCC(CC([O-])=O)=O.CCC(CC([O-])=O)=O.[Al+3].C1(=O)OC(C)CO1>[CH3:9][C:10](=[CH:5][CH:3]=[CH:2][C:1](=[O:7])[CH3:15])[CH3:11]
0.5
CC1COC(=O)O1
null
null
170
72
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
133,148
null
null
null
null
ord_dataset-34cf5f1378de4e34844aea93a2f9a9d3
1985-01-01T00:08:00
true
42 ml of triethylamine, 25 ml of isopropylamine, 250 ml of methylethylketone and 32 g of 2,4,6-trichloro-5-methoxypyrimidine (prepared as indicated by Budesinsky et Coll., Ceskoslov. Farm. 10, 241-247, 1961) were stirred together at 20° C. for 6 hours. The reaction mixture was then evaporated under reduced pressure and the residue fixed on a silica gel column. This was followed by elution with a 95/5 toluene-diethylamine mixture. In this way were isolated 20.2 g of 4-isopropylamino-2,6-dichloro-5-methoxypyrimidine.
COc1c(Cl)nc(Cl)nc1NC(C)C
null
COc1c(Cl)nc(Cl)nc1Cl
CC(C)N
null
C(N(CC)CC)C.[CH:8]([NH2:11])([CH3:10])[CH3:9].[Cl:12][C:13]1[N:18]=[C:17](Cl)[C:16]([O:20][CH3:21])=[C:15]([Cl:22])[N:14]=1>CC(CC)=O>[CH:8]([NH:11][C:17]1[C:16]([O:20][CH3:21])=[C:15]([Cl:22])[N:14]=[C:13]([Cl:12])[N:18]=1)([CH3:10])[CH3:9]
null
CCC(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
1,152,393
CN
null
null
null
ord_dataset-b195433d5c354ddfb6cde0d53c41910f
2012-01-01T00:04:00
true
To a solution of 6-chloro-N-methylnicotinoyl chloride (7.39 g, 42.0 mmol) in tetrahydrofuran (50 mL), methylamine (42 mL, 84.0 mmol) and triethylamine (6.4 mL, 46.2 mmol) were added under ice-cold conditions, and the resultant mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction solution was concentrated in vacuo, then filtered, and washed with tetrahydrofuran. The obtained residue was recrystallized (ethyl acetate/hexane) and 6-chloro-N-methylnicotinamide (6.52 g, yield 91%) was obtained as a white crystal.
CNC(=O)c1ccc(Cl)nc1
null
CCN(CC)CC
CN1CC(C(=O)Cl)=CC=C1Cl
null
[Cl:1][C:2]1[N:3](C)[CH2:4][C:5](=[CH:9][CH:10]=1)[C:6](Cl)=[O:7].CN.[CH2:14]([N:16](CC)CC)C>O1CCCC1>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:16][CH3:14])=[O:7])=[CH:4][N:3]=1
null
C1CCOC1
null
null
null
null
91
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
129,097
CC(C)(C)ON[C@H](C(=O)O)C(=C=O)CSCCNC(=O)OCc1ccccc1
CCOC(=O)[C@@H]1Cc2ccccc2CN1
O=C([O-])C(F)(F)F
null
ord_dataset-d6b60b593b1c4668bc6843cd65a5d232
1985-01-01T00:04:00
true
S-(2-Benzyloxycarbonylaminoethyl)-N-tert-butoxy-carbonyl-L-homocysteine (2.14 g., 0.00518 mole) and ethyl 1,2,3,4-tetrahydroisoquinoline-3-(S)-carboxylate (1.12 g., 0.00545 mole) were coupled via the procedure described in Example 5 to give 2.24 g. (72%) of ethyl N-[S-(2-benzyloxycarbonylaminoethyl)-N-tert-butoxycarbonyl-L-homocysteinyl]-1,2,3,4-tetrahydroisoquinoline-3-(S)-carboxylate (1); an oil. Compound 1 (1.10 g., 0.00183 mole) was stirred for 50 minutes at room temperature with 25 ml of trifluoroacetate acid. Concentration in vacuo gave ethyl N-[S-(2-benzyloxycarbonylaminoethyl)-L-homocysteinyl]1,2,3,4-tetrahydroisoquinoline-3-(S)-carboxylate (2) as a crude orange oil. This intermediate (2) was reductively alkylated with 2-oxo-4-phenylbutyric acid (3.00 g., 0.0068 mole) according to the procedure described in Example 5. After chromatography on an LH-20 column with methanol, 0.30 g. (25%) of ethyl N-[S-(2-benzyloxycarbonylaminoethyl)-N-(1-carboxy-3-phenylpropyl)-L-homocysteinyl]-1,2,3,4-tetrahydroisoquinoline-3-(S)-carboxylate (3) was obtained; a colorless oil.
CCOC(=O)[C@@H]1Cc2ccccc2CN1C(=O)[C@@H](N)CCSCCNC(=O)OCc1ccccc1
null
CCOC(=O)[C@@H]1Cc2ccccc2CN1C(=O)[C@H](CCSCCNC(=O)OCc1ccccc1)NC(=O)OC(C)(C)C
null
null
C(OC(NCCSCC(=C=O)[C@@H](C(O)=O)NOC(C)(C)C)=O)C1C=CC=CC=1.C1C2C(=CC=CC=2)C[C@@H](C(OCC)=O)N1.[CH2:44]([O:51][C:52]([NH:54][CH2:55][CH2:56][S:57][CH2:58][CH2:59][C@@H:60]([C:69]([N:71]1[C@H:80]([C:81]([O:83][CH2:84][CH3:85])=[O:82])[CH2:79][C:78]2[C:73](=[CH:74][CH:75]=[CH:76][CH:77]=2)[CH2:72]1)=[O:70])[NH:61]C(OC(C)(C)C)=O)=[O:53])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.FC(F)(F)C([O-])=O>>[CH2:44]([O:51][C:52]([NH:54][CH2:55][CH2:56][S:57][CH2:58][CH2:59][C@@H:60]([C:69]([N:71]1[C@H:80]([C:81]([O:83][CH2:84][CH3:85])=[O:82])[CH2:79][C:78]2[C:73](=[CH:74][CH:75]=[CH:76][CH:77]=2)[CH2:72]1)=[O:70])[NH2:61])=[O:53])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=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
640,908
null
null
null
null
ord_dataset-1c0bae7388cf460091d56129e95b3145
2004-01-01T00:06:00
true
The synthesis of the sulfonamide containing carboxylic acid precursor corresponding to the autoinducer analog 10 was accomplished by the two step sequence described below. Accordingly, a solution of α-toluenesulfonyl chloride (10 mmol) in CH2Cl2 (5 mL) was added dropwise to a stirred solution of octylamine (20 mmol) in CH2Cl2 (20 mL) at 0° C. The resulting mixture was subsequently stirred at room temperature for 30 min and was then extracted with H2O (3×24 mL) The organic phase was dried (MgSO4) and the solvent was evaporated in vacuo to provide the corresponding α-toluenesulfonamide (262 mg, 93%) as a colorless solid. Subsequent oxidative degradation of the phenyl moiety within this compound via the procedure of Sharpless, et al. [e.g., cat. RuCl3 hydrate, NaIO4, H2O/CH3CN/CCl4 (vide supra)] furnished the α-sulfonamidoacetic acid corresponding to homoserine lactone 10. Accordingly, a mixture of the above a-toluenesulfonamide (1.00 mmol), CCl4 (2 mL), CH3CN (2 mL), H2O (3 mL) and NaIO4 (14.50 mmol) was vigorously stirred at room temperature and RuCl3 hydrate (5 mg) was added. The reaction mixture was vigorously stirred for a further 2 h at room temperature and then CH2Cl2 (10 mL) was added and the phases were separated. The upper aqueous phase was extracted with three portions of CH2Cl2 and the combined organic phases were dried (MgSO4) and the solvents were removed in vacuo. Recrystallization of the residue from EtOH provided the α-sulfonamidoacetic acid (181 mg, 72%) as a colorless solid.
NS(=O)(=O)Cc1ccccc1
null
O=S(=O)(Cl)Cc1ccccc1
CCCCCCCCN
null
[C:1]1([CH2:7][S:8](Cl)(=[O:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([NH2:20])CCCCCCC>C(Cl)Cl>[C:1]1([CH2:7][S:8]([NH2:20])(=[O:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
0.5
ClCCl
null
null
25
15.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
68,176
[Mg]
null
null
null
ord_dataset-dabcd66611f34094b1baca0095305a66
1980-01-01T00:07:00
true
To 0.85 gm of magnesium in a thoroughly dried flask equipped with condensor and magnetic stirrer was added 5 mls of anhydrous tetrahydrofuran and 0.5 ml of dibromo ethane. A solution of 4.5 gms of 1,1-dimethoxy-9-chlorononane in 40 mls of toluene was added dropwise. When addition was half complete, a few drops of bromoethane were added and the addition was continued. The temperature was maintained at 75°±5° for two hours. The Grignard reagent was decanted into another flask and 100 mgs of cuprous chloride (CuCl) catalyst was added, followed by dropwise addition of 3.0 gms of a mixture (approximately 60:40) of 1-chloro-2-pentene and 3-chloro-1-pentene dissolved in 15 mls of toluene. The reaction flask was cooled in a water bath at 20°±5°. Magnesium chloride began to precipitate after ten minutes. The reaction stood overnight at room temperature. 50 mls of 3 N hydrochloric acid was added and the reaction mixture was stirred and heated at reflux for 1 hour. The aqueous layer was separated and washed two times with toluene. The organic layer and the toluene washes were combined and dried over sodium sulphate. The solvents were removed on the rotary evaporator and the residue was distilled at 83° at 0.10 torr yielding 2.3 gms of crude 11-tetradecenal. GLC analysis showed that the contaminating 10-ethyl-11-dodecenal was present in only 11.5%. For physical constants see Example 5.
CCC=CCCCCCCCCCC=O
null
CC(Br)Br
COC(CCCCCCCCCl)OC
C1CCOC1
[Mg].[O:2]1[CH2:6][CH2:5][CH2:4][CH2:3]1.Br[CH:8](Br)[CH3:9].CO[CH:13](OC)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]CCl>C1(C)C=CC=CC=1.BrCC>[CH:3](=[O:2])[CH2:4][CH2:5][CH2:6][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH:14]=[CH:13][CH2:8][CH3:9]
8
CCBr
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
742,677
C(=NC1CCCCC1)=NC1CCCCC1
Cl
On1nnc2ccccc21
null
ord_dataset-437aa6654d5044ddaef3346dc4c6e08a
2006-01-01T00:11:00
true
At 0° C. the solution of 746 mg (0.81 mmol) of HCl.Arg(Tos)-Pro-Ala-Lys(ClZ)-OBzl (SEQ ID NO: 12) in 50 ml of anhydrous tetrahydrofuran was adjusted to pH 9, to which the pre-cold solution of 340 mg (0.82 mmol) of Boc-Lys(ClZ)-OH, 110 mg (0.82 mmol) of 1-hydroxybenzotriazole and 170 mg (0.82 mmol) of dicyclohexylcarbodiimide in 40 ml of anhydrous tetrahydrofuran was added. The reaction mixture was stirred at 0° C. for 2 h and at room temperature for 16 h and TLC (chloroform/methanol, 10:1) indicated complete disappearance of HCl.Arg(Tos)-Pro-Ala-Lys(ClZ)-OBzl (SEQ ID NO: 12). The resulted precipitates of N,N-dicyclohexylurea were filtrated and the filtrate was diluted with 100 ml of ethyl acetate. The solution obtained was washed successively with saturated NaCO3 in water (50 ml×3), saturated NaCl in water (50 ml×3) and KHSO4 in water (5%, 50 ml×3). The separated ethyl acetate layer was dried with anhydrous MgSO4, and then evaporated. The residue was purified on sinica gel chromatography (CHCl3/CH3OH, 30/1) to provide 850 mg (81%) of the title compound as a glassy mass. Mp 78–88° C., FAB-MS (m/e) 1111.3[M+H]+, 1132.5[M+Na]+, 1010.0[M-Boc]+.
Cc1ccc(S(=O)(=O)NC(=N)NCCC[C@H](NC(=O)[C@H](CCCCNC(=O)OCc2ccccc2Cl)NC(=O)OC(C)(C)C)C(=O)N2CCC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)OCc2ccccc2Cl)C(=O)OCc2ccccc2)cc1
null
Cc1ccc(S(=O)(=O)NC(=N)NCCC[C@H](N)C(=O)N2CCC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)OCc2ccccc2Cl)C(=O)OCc2ccccc2)cc1
CC(C)(C)OC(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1Cl)C(=O)O
null
Cl.[NH2:2][C@H:3]([C:21]([N:23]1[CH2:62][CH2:61][CH2:60][C@H:24]1[C:25]([NH:27][C@H:28]([C:30]([NH:32][C@H:33]([C:50]([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51])[CH2:34][CH2:35][CH2:36][CH2:37][NH:38][C:39]([O:41][CH2:42][C:43]1[CH:49]=[CH:48][CH:47]=[CH:46][C:44]=1[Cl:45])=[O:40])=[O:31])[CH3:29])=[O:26])=[O:22])[CH2:4][CH2:5][CH2:6][NH:7][C:8](=[NH:20])[NH:9][S:10]([C:13]1[CH:19]=[CH:18][C:16]([CH3:17])=[CH:15][CH:14]=1)(=[O:12])=[O:11].[NH:63]([C:84]([O:86][C:87]([CH3:90])([CH3:89])[CH3:88])=[O:85])[C@H:64]([C:81](O)=[O:82])[CH2:65][CH2:66][CH2:67][CH2:68][NH:69][C:70]([O:72][CH2:73][C:74]1[CH:80]=[CH:79][CH:78]=[CH:77][C:75]=1[Cl:76])=[O:71].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.C(Cl)(Cl)Cl.CO>[NH:63]([C:84]([O:86][C:87]([CH3:90])([CH3:89])[CH3:88])=[O:85])[C@H:64]([C:81]([NH:2][C@H:3]([C:21]([N:23]1[CH2:62][CH2:61][CH2:60][C@H:24]1[C:25]([NH:27][C@H:28]([C:30]([NH:32][C@H:33]([C:50]([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51])[CH2:34][CH2:35][CH2:36][CH2:37][NH:38][C:39]([O:41][CH2:42][C:43]1[CH:49]=[CH:48][CH:47]=[CH:46][C:44]=1[Cl:45])=[O:40])=[O:31])[CH3:29])=[O:26])=[O:22])[CH2:4][CH2:5][CH2:6][NH:7][C:8](=[NH:20])[NH:9][S:10]([C:13]1[CH:14]=[CH:15][C:16]([CH3:17])=[CH:18][CH:19]=1)(=[O:11])=[O:12])=[O:82])[CH2:65][CH2:66][CH2:67][CH2:68][NH:69][C:70]([O:72][CH2:73][C:74]1[CH:80]=[CH:79][CH:78]=[CH:77][C:75]=1[Cl:76])=[O:71]
16
ClC(Cl)Cl
CO
C1CCOC1
0
null
81
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
530,974
O=C([O-])[O-]
[K+]
null
null
ord_dataset-7774db17e619477ea20ee621abe71257
2002-01-01T00:01:00
true
3.0 g of 4-chloro-5-formyl-2-phenylimidazole (Chem. Pharm. Bull. 1976, 24(5), 960), 7.0 g of 4-bromobenzyl bromide and 11.7 g of K2CO3 are stirred at RT for 20 h in 200 ml of DMF. The reaction mixture is then poured onto 500 ml of water, and the precipitate is filtered off with suction and chromatographed on silica gel using DIP. 3.9 g of an amorphous foam are obtained.
O=Cc1c(Cl)nc(-c2ccccc2)n1Cc1ccc(Br)cc1
null
BrCc1ccc(Br)cc1
O=Cc1[nH]c(-c2ccccc2)nc1Cl
null
[Cl:1][C:2]1[N:3]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[NH:5][C:6]=1[CH:7]=[O:8].[Br:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20]Br)=[CH:18][CH:17]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[Br:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20][N:5]2[C:6]([CH:7]=[O:8])=[C:2]([Cl:1])[N:3]=[C:4]2[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:18][CH:17]=1
null
O
CN(C)C=O
null
null
71.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,132,807
null
null
null
null
ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820
2012-01-01T00:02:00
true
A mixture of tert-butyl 2-(4-(1-oxo-6-propylisoindolin-2-yl)phenyl)propanoate (0.084 g, 0.22 mmol) and formic acid (15 mL) was stirred overnight at room temperature. The mixture was then concentrated under reduced pressure, suspended in hexanes (5 mL), sonicated, and the solid collected by filtration to afford 2-(4-(1-oxo-6-propylisoindolin-2-yl)phenyl)propanoic acid (0.041 g, 57%) as a white solid: mp 175-177° C.; 1H NMR (300 MHz, CDCl3) δ 7.83 (d, J=8.6 Hz, 2H), 7.74 (s, 1H), 7.41-7.37 (m, 4H), 4.81 (s, 2H), 3.77 (q, J=7.1 Hz, 1H), 2.70 (t, J=7.4 Hz, 2H), 1.73-1.65 (m, 2H), 1.54 (d, J=7.2 Hz, 3H), 0.95 (t, J=7.3 Hz, 3H); ESI MS m/z 324 [M+H]+.
CCCc1ccc2c(c1)C(=O)N(c1ccc(C(C)C(=O)O)cc1)C2
null
CCCc1ccc2c(c1)C(=O)N(c1ccc(C(C)C(=O)OC(C)(C)C)cc1)C2
null
null
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:11][CH2:12][CH3:13])[CH:9]=2)[CH2:4][N:3]1[C:14]1[CH:19]=[CH:18][C:17]([CH:20]([CH3:28])[C:21]([O:23]C(C)(C)C)=[O:22])=[CH:16][CH:15]=1>C(O)=O>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH2:11][CH2:12][CH3:13])[CH:9]=2)[CH2:4][N:3]1[C:14]1[CH:19]=[CH:18][C:17]([CH:20]([CH3:28])[C:21]([OH:23])=[O:22])=[CH:16][CH:15]=1
8
O=CO
null
null
25
57.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
374,748
Cc1ccc(S(=O)(=O)O)cc1
null
null
null
ord_dataset-ee5599340390470d8e5b5ac1feddf9d6
1997-01-01T00:08:00
true
The alcohol of Example 17 is dissolved in 5 mL of nitro ethyl acetate. A catalytic amount of p-toluene-sulfonic acid is added and the reaction mixture is heated to 120° C. for 3 hours. Excess nitro ethyl acetate is removed by distillation and the residue is purified by silica gel chromatography eluting with 15% ethyl acetate-hexane to give 2.25 g (79%) of product as a yellow oil;
CCOC(=O)C(C(c1ccc2c(c1)OCO2)c1ccc2c(c1)OCO2)[N+](=O)[O-]
null
CCOC(=O)C[N+](=O)[O-]
OC(c1ccc2c(c1)OCO2)c1ccc2c(c1)OCO2
null
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([C:12]3[CH:20]=[CH:19][C:15]4[O:16][CH2:17][O:18][C:14]=4[CH:13]=3)O)=[CH:9][C:4]=2[O:3][CH2:2]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:32][CH2:33][O:34][C:35]([CH2:37][N+:38]([O-:40])=[O:39])=[O:36]>>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([C:12]3[CH:20]=[CH:19][C:15]4[O:16][CH2:17][O:18][C:14]=4[CH:13]=3)[CH:37]([N+:38]([O-:40])=[O:39])[C:35]([O:34][CH2:33][CH3:32])=[O:36])=[CH:9][C:4]=2[O:3][CH2:2]1
null
null
null
null
120
null
79
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
568,700
[H-]
[Na+]
null
null
ord_dataset-5e1b2445a3d94ea592ddf2c284118a1e
2002-01-01T00:11:00
true
The product from Example 21, step e) (0.4 g, 0.0009 mol) and (2-methyl-2H-[1,2,4]triazol-3-yl)methanol (0.12 g, 0.0011 mol) were dissolved in dry N,N-dimethylformamide (10 ml) under nitrogen and sodium hydride (60% wt in oil) (0.035 g, 0.0009 mol) was added. The solution was stirred at room temperature for 3 h after which solvent was removed in vacuo and the residue was purified using silica gel chromatography with 0%→60% ethyl acetate/dichloromethane as eluent. Trituration with isohexane and recrystallisation from ethyl acetate/isohexane gave the required product (0.137 g, mp=144° C.). Data for the title compound: 1H NMR (400 MHz, CDCl3) δ 1.50 (9H, s), 3.84 (3H, s), 5.48 (2H, s), 7.18-7.26 (1H, m), 7.27-7.35 (1H, m), 7.47 (1H, m), 7.87 (1H, s), 9.41 (1H, s); MS (ES+) m/e 400 [MH]+; Anal. Found: C, 57.30; H, 4.64; N, 24.64%. C19H19F2N7O requires: C, 57.14; H, 4.79; N, 24.55%.
Cn1ncnc1COc1nn2c(-c3cc(F)ccc3F)nncc2c1C(C)(C)C
null
Cn1ncnc1CO
Cc1ccc(S(=O)(=O)Oc2nn3c(-c4cc(F)ccc4F)nncc3c2C(C)(C)C)cc1
null
[C:1]([C:5]1[C:6]([O:22]S(C2C=CC(C)=CC=2)(=O)=O)=[N:7][N:8]2[C:13]=1[CH:12]=[N:11][N:10]=[C:9]2[C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[F:21])([CH3:4])([CH3:3])[CH3:2].[CH3:33][N:34]1[C:38]([CH2:39]O)=[N:37][CH:36]=[N:35]1.[H-].[Na+]>CN(C)C=O>[F:21][C:15]1[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:14]=1[C:9]1[N:8]2[N:7]=[C:6]([O:22][CH2:39][C:38]3[N:34]([CH3:33])[N:35]=[CH:36][N:37]=3)[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[C:13]2[CH:12]=[N:11][N:10]=1
3
CN(C)C=O
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,217,793
CC(C)(C)[O-]
Cl
[K+]
null
ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777
2012-01-01T00:10:00
true
Bis(dibenzylidineacetone)palladium (2 mg, 0.0035 mmol) and (2′-dicyclohexyl phosphanyl-biphenyl-2-yl)-dimethylamine (3.3 mg, 0.0084 mmol) were added to dry toluene (10 mL purged with argon) and stirred for 15 minutes under argon. Potassium tert-butoxide (197 mg, 1.75 mmol), 6-methoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride salt (134 mg, 0.67 mmol) and N-(4-bromo-2,6-dimethyphenyl)-3,3-dimethylbutanamide (200 mg, 0.67 mmol) were then added and the reaction mixture was stirred at 80° C. overnight. The reaction mixture was then cooled to room temperature, concentrated, filtered through a pad of silica gel, and recrystallized from toluene to afford the title compound as a solid.
COc1ccc2c(c1)CCN(c1cc(C)c(NC(=O)CC(C)(C)C)c(C)c1)C2
null
Cc1cc(Br)cc(C)c1NC(=O)CC(C)(C)C
COc1ccc2c(c1)CCNC2
null
CC(C)([O-])C.[K+].Cl.[CH3:8][O:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[CH2:16][NH:15][CH2:14][CH2:13]2.Br[C:21]1[CH:26]=[C:25]([CH3:27])[C:24]([NH:28][C:29](=[O:35])[CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[C:23]([CH3:36])[CH:22]=1>C1(C)C=CC=CC=1>[CH3:8][O:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[CH2:16][N:15]([C:21]1[CH:26]=[C:25]([CH3:27])[C:24]([NH:28][C:29](=[O:35])[CH2:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[C:23]([CH3:36])[CH:22]=1)[CH2:14][CH2:13]2
0.25
Cc1ccccc1
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null