original_index
int64
2
1.77M
extracted_from_file
stringclasses
489 values
date_of_experiment
timestamp[ns]date
grant_date
timestamp[ns]date
1976-01-01 00:01:00
2016-01-01 00:09:00
is_mapped
bool
1 class
rxn_str
stringlengths
87
6.12k
reactant_000
stringlengths
1
902
reactant_001
stringlengths
1
902
reactant_002
null
agent_000
stringlengths
1
540
agent_001
stringlengths
1
852
agent_002
stringlengths
1
247
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_000
stringclasses
446 values
solvent_001
stringclasses
405 values
solvent_002
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
temperature
float64
-230
30.1k
rxn_time
float64
0
2.16k
procedure_details
stringlengths
8
24.5k
product_000
stringlengths
1
484
product_001
null
yield_000
float64
0
90,205,156,600B
yield_001
float64
0
100M
1,531,591
ord_dataset-8d5c200bca27407ab9febe7598e16458
null
2015-01-01T00:01:00
true
Cl.[NH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10]([C:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([C:21]4[CH:26]=[C:25]([CH:27]([CH3:29])[CH3:28])[CH:24]=[CH:23][C:22]=4[O:30][CH2:31][CH:32]4[CH2:34][CH2:33]4)[C:15]=3[NH:14][C:13]=2[CH3:35])=[O:11])[CH2:5][CH2:4]1.[C:36](Cl)(=[O:38])[CH3:37]>>[C:36]([NH:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([NH:9][C:10]([C:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([C:21]4[CH:26]=[C:25]([CH:27]([CH3:29])[CH3:28])[CH:24]=[CH:23][C:22]=4[O:30][CH2:31][CH:32]4[CH2:33][CH2:34]4)[C:15]=3[NH:14][C:13]=2[CH3:35])=[O:11])[CH2:5][CH2:4]1)(=[O:38])[CH3:37]
CC(=O)Cl
Cc1[nH]c2c(-c3cc(C(C)C)ccc3OCC3CC3)ncnc2c1C(=O)N[C@H]1CC[C@H](N)CC1
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
Starting from N-(trans-4-aminocyclohexyl)-4-[2-(cyclopropylmethoxy)-5-(propan-2-yl)phenyl]-6-methyl-5H-pyrrolo[3,2-d]pyrimidine-7-carboxamide hydrochloride (example D.f53) and commercially available acetyl chloride the title compound is obtained as colorless solid.
CC(=O)N[C@H]1CC[C@H](NC(=O)c2c(C)[nH]c3c(-c4cc(C(C)C)ccc4OCC4CC4)ncnc23)CC1
null
null
null
1,512,447
ord_dataset-1a1aa5d1c3224edca0aec6e3398da985
null
2014-01-01T00:11:00
true
[C:1]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=S)[C:10]([C:19]([O:21]CC)=O)=[CH:9]2)=[CH:3][CH:2]=1.[C:30]1([NH:36][NH2:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C>C(O)C>[C:1]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:2]=[CH:3][C:4]([CH2:7][N:8]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[C:11]3=[N:37][N:36]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[C:19](=[O:21])[C:10]3=[CH:9]2)=[CH:5][CH:6]=1
CCOC(=O)c1cn(Cc2ccc(-c3ccccc3)cc2)c2ccccc2c1=S
NNc1ccccc1
null
CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCO
null
null
null
null
null
null
null
null
null
null
25
18
Ethyl 1-(biphenyl-4-ylmethyl)-4-thioxo-1,4-dihydroquinoline-3-carboxylate [(Example 8, Step 2), 72 mg, 0.18 mmol] and phenylhydrazine (0.19 g, 1.8 mmol, 10 equiv) were combined in absolute ethanol (5 mL) and placed into a preheated oil bath at 75° C. for 18 hours. The mixture was cooled to ambient temperature and concentrated in vacuo. The residue was dissolved in dichloromethane (10 mL) and treated with di-tert-butyldicarbonate (0.30 g, 1.4 mmol, 7.8 equiv). After stirring for 5 hours at ambient temperature, the mixture was concentrated in vacuo and the residue was purified by silica gel gradient chromatography (100:0 to 95:5; dichloromethane:methanol), providing the titled compound: 1H-NMR (500 MHz, d6-DMSO) δ 9.17 (1H, s), 8.31 (1H, dd, J=7.8, 1.4 Hz), 8.22 (2H, d, J=7.6 Hz), 7.81 (1H, d, J=8.8 Hz), 7.67-7.62 (5H, m), 7.57 (1H, t, J=7.8 Hz), 7.48-7.40 (6H, m), 7.35 (1H, t, J=7.4 Hz), 7.20 (1H, t, J=7.4 Hz), 5.80 (2H, s) ppm; high resolution mass spectrometry (ES+) m/z 428.1757 [(M+H)+; calculated for C29H22N3O: 428.1758].
O=c1c2cn(Cc3ccc(-c4ccccc4)cc3)c3ccccc3c-2nn1-c1ccccc1
null
null
null
200,612
ord_dataset-31f00a039ca0424788e5e1970d25a8fd
null
1989-01-01T00:12:00
true
[CH2:1]([N:3]([CH2:12][CH3:13])[C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1)[CH3:2].[N+:14]([C:17]1[CH:22]=[CH:21][C:20]([CH2:23]C(O)=O)=[CH:19][CH:18]=1)([O-:16])=[O:15].N1CCCCC1>O>[CH2:1]([N:3]([CH2:12][CH3:13])[C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[CH:23][C:20]2[CH:21]=[CH:22][C:17]([N+:14]([O-:16])=[O:15])=[CH:18][CH:19]=2)=[CH:6][CH:5]=1)[CH3:2]
O=C(O)Cc1ccc([N+](=O)[O-])cc1
CCN(CC)c1ccc(C=O)cc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1CCNCC1
O
null
null
null
null
null
null
null
null
null
0
null
A mixture of 5.00 g (28 mmol) of 4-diethylaminobenzaldehyde, 5.62 g (31 mmol) of 4-nitrophenylacetic acid, 2.40 g (28 mmol) of piperidine, and 100 mL of xylenes was heated with stirring at reflux for 20 hours with continuous removal of water using a Dean-Stark apparatus. The mixture turned dark red. Approximately half the xylenes was distilled, and the residue was cooled to 3 0° C. Red crystals separated which were collected and then recrystallized from isopropanol/pyridine. Yield: 4.05 g (48%), mp 179-181 (lit2 182°-182.5° C.).
CCN(CC)c1ccc(C=Cc2ccc([N+](=O)[O-])cc2)cc1
null
null
null
1,242,369
ord_dataset-c544c0c663f54dbea4ddb52ddde7934e
null
2013-01-01T00:01:00
true
[OH:1][C@@H:2]([C@H:4]1[C:24](=[O:25])[N:6]2[C:7]([C:21]([O-:23])=[O:22])=[C:8]([S:11]/[CH:12]=[CH:13]\[C:14]3[S:18][CH:17]=[N:16][C:15]=3[CH2:19][OH:20])[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].[Na+].[N:27]1([C:33]([O:35][CH2:36]I)=[O:34])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[OH:1][C@@H:2]([C@H:4]1[C:24](=[O:25])[N:6]2[C:7]([C:21]([O:23][CH2:36][O:35][C:33]([N:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)=[O:34])=[O:22])=[C:8]([S:11]/[CH:12]=[CH:13]\[C:14]3[S:18][CH:17]=[N:16][C:15]=3[CH2:19][OH:20])[C@H:9]([CH3:10])[C@H:5]12)[CH3:3]
O=C(OCI)N1CCCCC1
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(S/C=C\c3scnc3CO)[C@H](C)[C@H]12
null
[Na+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
In the same manner as in Example 81, 192 mg of the title compound was prepared from 160 mg of sodium (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-2-[[(Z)-2-(4-hydroxymethylthiazol-5-yl)ethen-1-yl]thio]-1-methyl-1-carbapen-2-em-3-carboxylate and 130 mg of (piperidin-1-yl)carbonyloxymethyl iodide.
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCOC(=O)N3CCCCC3)=C(S/C=C\c3scnc3CO)[C@H](C)[C@H]12
null
92.7
null
139,528
ord_dataset-7d359d96b3a64882921ebdc6c850e22e
null
1986-01-01T00:01:00
true
C(OC([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C@H:18]([NH:24][C@@H:25]1[C:31](=[O:32])[N:30]([CH2:33][C:34]([O:36]C(C)(C)C)=[O:35])[C:29]2[CH:41]=[CH:42][CH:43]=[CH:44][C:28]=2[S:27][CH2:26]1)[C:19]([O:21][CH2:22][CH3:23])=[O:20])=O)(C)(C)C.C(OCC)(=O)C.[ClH:51]>CCOCC>[ClH:51].[ClH:51].[NH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C@H:18]([NH:24][C@@H:25]1[C:31](=[O:32])[N:30]([CH2:33][C:34]([OH:36])=[O:35])[C:29]2[CH:41]=[CH:42][CH:43]=[CH:44][C:28]=2[S:27][CH2:26]1)[C:19]([O:21][CH2:22][CH3:23])=[O:20]
CCOC(=O)[C@H](CCCCCCCCCNC(=O)OC(C)(C)C)N[C@H]1CSc2ccccc2N(CC(=O)OC(C)(C)C)C1=O
null
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCOC(C)=O
CCOCC
null
null
null
null
null
null
null
null
null
null
null
A solution of tert-butyl 3(R)-[10-tert-butoxycarbonylamino-1(S)-ethoxycarbonyldecyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate (0.3 g) in a hydrogen chloride-ethyl acetate solution (5N, 10 ml) stands for 3 hours at room temperature, and then a mixture of ether and petroleum ether is added. After agitating thoroughly, the supernatant is removed by decantation. The deposited precipitate is dried under reduced pressure to provide 3(R)-[10-amino-1(S)-ethoxycarbonyldecyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid dihydrochloride (0.23) g as a colorless powder.
CCOC(=O)[C@H](CCCCCCCCCN)N[C@H]1CSc2ccccc2N(CC(=O)O)C1=O
null
null
null
1,690,319
ord_dataset-c1e70ad912eb438f8d34b1dc681f809a
null
2016-01-01T00:02:00
true
[OH:1][C@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C@:3]1([CH2:20][C:21]1[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=1)[C:11]1[CH2:12][C:13]2[C:18]([CH:19]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.[N:45]1C=CC=CC=1.C(=O)(O)[O-].[NH4+]>CS(C)=O.O>[OH:1][C@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C@:3]1([CH2:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([NH2:45])=[O:26])=[CH:23][CH:22]=1)[C:11]1[CH2:12][C:13]2[C:18]([CH:19]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2
O=C(O)c1ccc(C[C@]2(C3=Cc4ccccc4C3)Cc3ccccc3[C@@H]2O)cc1
c1ccncc1
null
CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
O=C([O-])O
[NH4+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
O
CS(C)=O
null
null
null
null
null
null
null
null
null
25
0.08
To a solution of 4-(((1R,2R)-1-hydroxy-2,3-dihydro-1H,1′H-[2,2′-biinden]-2-yl)methyl)benzoic acid (100 mg, 0.26 mmol) in DMSO (5 mL) was added Boc anhydride (69 mg, 0.31 mmol) followed by pyridine (24 mg, 0.26 mmol) and stirred at room temperature for 5 min. Ammonium bicarbonate (62 mg, 0.78 mmol) was added and stirred for additional 1 h. Reaction mixture was poured into water (25 mL) and extracted with ethyl acetate (3×25 mL). The organic layer was washed with brine (25 mL), dried over anhydrous Na2SO4 and evaporated under reduced pressure. The residue was purified by CombiFlash using 20% ethyl acetate in chloroform as an eluent to yield 59 mg (59%) of the title compound as an off white solid.
NC(=O)c1ccc(C[C@]2(C3=Cc4ccccc4C3)Cc3ccccc3[C@@H]2O)cc1
null
59.5
null
1,703,250
ord_dataset-54347fcace774f89850681d6dec8009f
null
2016-01-01T00:03:00
true
[CH3:1][C:2]1[CH:3]=[C:4]([N:9]2[CH:13]=[CH:12][C:11]([NH2:14])=[N:10]2)[CH:5]=[CH:6][C:7]=1[CH3:8].N1C=CC=CC=1.[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([N+:31]([O-:33])=[O:32])=[C:26]([CH:30]=1)[C:27](Cl)=[O:28]>ClCCl>[Cl:21][C:22]1[CH:23]=[CH:24][C:25]([N+:31]([O-:33])=[O:32])=[C:26]([CH:30]=1)[C:27]([NH:14][C:11]1[CH:12]=[CH:13][N:9]([C:4]2[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([CH3:1])[CH:3]=2)[N:10]=1)=[O:28]
Cc1ccc(-n2ccc(N)n2)cc1C
O=C(Cl)c1cc(Cl)ccc1[N+](=O)[O-]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
c1ccncc1
ClCCl
null
null
null
null
null
null
null
null
null
25
2
Into a 100-mL round bottom flask, was placed a solution of 1-(3,4-dimethylphenyl)-1H-pyrazol-3-amine (408 mg, 2.18 mmol, 1.00 equiv) in dichloromethane (10 mL), pyridine (518 mg, 6.56 mmol, 3.00 equiv), and 5-chloro-2-nitrobenzoyl chloride (575 mg, 2.61 mmol, 1.00 equiv). The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The solution was adjusted to pH 7 with hydrochloric acid (1 mol/L). The resulting solution was extracted with 3×50 mL of ethyl acetate and the organic layers combined dried over anhydrous sodium sulfate, and concentrated under vacuum. This resulted in 600 mg (59%) of 5-chloro-N-(1-(3,4-dimethylphenyl)-1H-pyrazol-3-yl)-2-nitrobenzamide as a yellow solid.
Cc1ccc(-n2ccc(NC(=O)c3cc(Cl)ccc3[N+](=O)[O-])n2)cc1C
null
null
null
1,719,696
ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb
null
2016-01-01T00:04:00
true
[CH3:1][CH:2]([OH:4])[CH3:3].[H-].[Na+].[Cl:7][C:8]1[CH:13]=[N:12][CH:11]=[C:10](Cl)[N:9]=1>C1COCC1>[Cl:7][C:8]1[CH:13]=[N:12][CH:11]=[C:10]([O:4][CH:2]([CH3:3])[CH3:1])[N:9]=1
Clc1cncc(Cl)n1
CC(C)O
null
[H-]
[Na+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1CCOC1
null
null
null
null
null
null
null
null
null
null
null
0.25
To a solution of 2-propanol (2.26 mL, 31.99 mmol) in dry THF (40 mL) was added 60% NaH (960 mg, 39.90 mmol) at 0° C. and the reaction was stirred for 15 min. To the mixture at 0° C. was added 2,6-dichloropyrazine (4 g, 26.66 mmol, Aldrich) and the reaction was stirred for 2 h at RT. The reaction was quenched with ice cold H2O (20 mL) and extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified with silica gel column chromatography (eluent: 100% petroleum ether) to afford 2-chloro-6-isopropoxypyrazine (4.0 g, 86%) as an off brown liquid. MS (ESI, pos. ion) m/z: 173.0 (M+1); 1H NMR (400 MHz, CDCl3): δ 8.28 (s, 1H), 8.14 (s, 1H), 5.31-5.25 (m, 1H), 1.37-1.36 (m, 6H).
CC(C)Oc1cncc(Cl)n1
null
86.9
null
1,205,954
ord_dataset-fb72428f30234761b4216139dc228d0c
null
2012-01-01T00:09:00
true
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][N:11]=[N:10][N:9]=2)=[CH:4][CH:3]=1.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21]1[C:29]2[C:24](=[N:25][CH:26]=[C:27](B3OC(C)(C)C(C)(C)O3)[CH:28]=2)[N:23](COCC[Si](C)(C)C)[N:22]=1>O1CCCC1.C(#N)C>[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21]1[C:29]2[C:24](=[N:25][CH:26]=[C:27]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[NH:12][N:11]=[N:10][N:9]=4)=[CH:4][CH:3]=3)[CH:28]=2)[NH:23][N:22]=1
Brc1ccc(-c2nnn[nH]2)cc1
COc1ccccc1-c1nn(COCC[Si](C)(C)C)c2ncc(B3OC(C)(C)C(C)(C)O3)cc12
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1CCOC1
CC#N
null
null
null
null
null
null
null
null
null
25
16
In a microwave vial 5-(4-bromo-phenyl)-1H-tetrazole (89.2 mg, 0.4 mmol), 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (200 mg, 0.40 mmol) in tetrahydrofuran/aceto-nitrile/1 N aqueous sodium bicarbonate (4 ml) was degassed with nitrogen and 1,1′-bis-(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct (32.4 mg, 0.04 mmol) was added and the vial sealed. This reaction mixture was irradiated to 150° C. for 30 minutes in a microwave reactor. The mixture was extracted with ethyl acetate (3×) and the combined organic layers were dried over magnesium sulfate and filtered through a silica gel plug MS: m/z 500.6 (M+H+). To this crude was added trifluoroacetic acid (1 ml) and the reaction mixture stirred for 16 hours at ambient temperature. The solvent was removed under reduced pressure and the resulting solid was purified by preparative mass-triggered reverse-phase HPLC to yield 3-(2-methoxy-phenyl)-5-[4-(1H-tetrazol-5-yl)-phenyl]-1H-pyrazolo[3,4-b]pyridine as a white solid (7.5 mg, 5%). 1H NMR (500 MHz, DMSO-d6) δ 3.87 (s, 3H); 6.56 (s, 3H); 7.11 (t, J=8 Hz 1H) 7.23 (d, J=8 Hz 1H); 7.48 (t, J=8 Hz, 1H); 7.66 (d, J=8 Hz 1H); 8.01 (t, J=9 Hz, 1H); 8.14 (d, J=9 Hz 1H); 8.44 (s, 1H); 8.94 (s, 1H); 13.84 (s, br, 1H); MS: m/z 369.3 (M+H+).
COc1ccccc1-c1n[nH]c2ncc(-c3ccc(-c4nnn[nH]4)cc3)cc12
null
5.1
null
1,079,289
ord_dataset-afd812677c134591a99f46ce28de2524
null
2011-01-01T00:08:00
true
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([NH2:12])=[CH:5]2.[CH3:13][O-:14].[Na+]>CS(C)=O>[CH3:13][O:14][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([NH2:12])=[CH:5]2
C[O-]
Nc1cc2cc(Br)ccc2cn1
null
[Na+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CS(C)=O
null
null
null
null
null
null
null
null
null
null
150
null
In a dry box, to the microwave test tube (20 ml volume) was added the 6-bromoisoquinolin-3-amine (1.0 g, 4.5 mmol) and the NaOMe (242.0 mg, 4.5 mmol) in 10 ml of DMSO. The microwave test tube was capped and moved from the dry box. The test tube was place into Microwave station to heat at 150° C. for 30 min. The crude residue was purified by a silica gel column to give 420 mg (yield 53.8%). 1H NMR (400 MHz, DMSO-d6) ppm 2.44 (s, 3H), 7.94-8.11 (m, 2H), 8.17 (d, J=8.56 Hz, 2H), 8.82 (s, 1H). MS m/z, (APCI); 175.1 ([M+H]+).
COc1ccc2cnc(N)cc2c1
null
53.8
null
1,714,559
ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb
null
2016-01-01T00:04:00
true
Br[C:2]1[S:6][C:5]([CH:7]=[O:8])=[CH:4][CH:3]=1.[F:9][C:10]([F:18])([F:17])[CH2:11][CH2:12][B-](F)(F)F>>[F:9][C:10]([F:18])([F:17])[CH2:11][CH2:12][C:2]1[S:6][C:5]([CH:7]=[O:8])=[CH:4][CH:3]=1
F[B-](F)(F)CCC(F)(F)F
O=Cc1ccc(Br)s1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
The compound was synthesized as in Example 3.1 using 5-bromothiophene-2-carbaldehyde (250 mg, 1.31 mmol) in place of 5-bromo-2-formylfuran and 3,3,3-trifluoropropyltrifluoroborate (440 mg, 2.16 mmol) in place of hexylboronic acid to give 5-(3,3,3-trifluoropropyl)thiophene-2-carbaldehyde (244 mg, 90%). Used without further characterization.
O=Cc1ccc(CCC(F)(F)F)s1
null
89.5
null
11,257
ord_dataset-7c810806c4564bada4a9550135bbb06f
null
1976-01-01T00:08:00
true
[CH3:1][C:2]1[CH:7]=[CH:6][CH2:5][C:4]([CH3:9])([CH3:8])[C:3]=1[C:10](=[O:14])/[CH:11]=[CH:12]/[CH3:13]>O1CCOCC1>[CH3:1][C:2]12[C:12]([CH3:13])=[CH:11][C:10](=[O:14])[CH:3]1[C:4]([CH3:8])([CH3:9])[CH2:5][CH:6]=[CH:7]2
C/C=C/C(=O)C1=C(C)C=CCC1(C)C
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1COCCO1
null
null
null
null
null
null
null
null
null
null
null
null
A solution of 2,6,6-trimethyl-1-crotonoyl-1,3-cyclohexadiene (1.0 g.) in 10 ml. of dioxan was heated under the same conditions as described in Example 49 with acidic diatomaceous earth (0.2 g.).
CC1=CC(=O)C2C(C)(C)CC=CC12C
null
null
null
762,098
ord_dataset-2e58cb8db2bf482bbea23283b7e04488
null
2007-01-01T00:03:00
true
[N:1]([C@H:4]1[CH2:9][CH2:8][C@H:7]([C:10]([O:12]C)=[O:11])[CH2:6][C@H:5]1[NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[N+:2]=[N-:3].[OH-].[Li+].O>O1CCCC1>[N:1]([C@H:4]1[CH2:9][CH2:8][C@H:7]([C:10]([OH:12])=[O:11])[CH2:6][C@H:5]1[NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[N+:2]=[N-:3]
COC(=O)[C@H]1CC[C@H](N=[N+]=[N-])[C@H](NC(=O)OC(C)(C)C)C1
null
null
[Li+]
[OH-]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1CCOC1
O
null
null
null
null
null
null
null
null
null
25
36.5
(1S,2R,4S)-1-Azido-2-(N-tert-butoxycarbonylamino)-4-methoxycarbonylcyclohexane (509 mg) was dissolved in tetrahydrofuran (40.0 ml), lithium hydroxide (111 mg) and water (5.0 ml) were successively added under ice cooling, and the mixture was stirred at room temperature for 36.5 hours. The solvent was distilled off under reduced pressure, water and 1N hydrochloric acid (4.64 ml) were added to the residue, and the solvent was distilled off again under reduced pressure to obtain crude (1S,2R,4S)-1-azido-2-(N-tert-butoxycarbonylamino)-4-carboxycyclohexane. Dichloromethane (25 ml) and N,N-dimethylformamide (260 μl) were added to this crude product, and the mixture was stirred under ice cooling. Further, oxalyl chloride (216 μl) was added to continuously stir the mixture at room temperature for 1 hour. tert-Butylamine (1130 μl) was added to the reaction mixture under ice cooling to stir the mixture at room temperature for 14 hours. After water and dichloromethane were added to the reaction mixture to conduct liquid separation, the resultant organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by flash column chromatography on silica gel (hexane:ethyl acetate=2:1) to obtain the title compound (197 mg) as a pale yellow amorphous substance.
CC(C)(C)OC(=O)N[C@@H]1C[C@@H](C(=O)O)CC[C@@H]1N=[N+]=[N-]
null
null
null
1,076,295
ord_dataset-afd812677c134591a99f46ce28de2524
null
2011-01-01T00:08:00
true
[CH2:1]([N:8](C)[CH2:9][CH2:10][O:11][CH2:12][CH:13]1[CH2:20][N:19]2[C:21]3[CH:22]=[C:23]([C:34]([NH:36][S:37]([N:40]([CH2:42][CH:43]([O:46][CH3:47])[O:44][CH3:45])[CH3:41])(=[O:39])=[O:38])=[O:35])[CH:24]=[CH:25][C:26]=3[C:27]([CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)=[C:18]2[C:17]2[CH:48]=[CH:49][CH:50]=[CH:51][C:16]=2[O:15][CH2:14]1)C1C=CC=CC=1.CC(O)=O>CO.[Pd]>[CH:28]1([C:27]2[C:26]3[CH:25]=[CH:24][C:23]([C:34]([NH:36][S:37]([N:40]([CH2:42][CH:43]([O:46][CH3:47])[O:44][CH3:45])[CH3:41])(=[O:39])=[O:38])=[O:35])=[CH:22][C:21]=3[N:19]3[C:18]=2[C:17]2[CH:48]=[CH:49][CH:50]=[CH:51][C:16]=2[O:15][CH2:14][CH:13]([CH2:12][O:11][CH2:10][CH2:9][NH:8][CH3:1])[CH2:20]3)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]1
COC(CN(C)S(=O)(=O)NC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CC(COCCN(C)Cc1ccccc1)COc1ccccc1-3)OC
null
null
[Pd]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CC(=O)O
CO
null
null
null
null
null
null
null
null
null
null
12
A solution of (7R or 7S)-7-({2-[benzyl(methyl)amino]ethoxy}methyl)-14-cyclohexyl-N-{[(2,2-dimethoxyethyl)(methyl)amino]sulfonyl}-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxamide in MeOH (0.06 M) was treated with AcOH (1 eq) and Pd/C (2 eq). The resulting mixture was stirred for 12 h under an H2 atmosphere. The mixture was filtered and then concentrated in vacuo to afford the title compound. The crude material was used in the next step without further purification. (ES+) m/z 643 (M+H)+.
CNCCOCC1COc2ccccc2-c2c(C3CCCCC3)c3ccc(C(=O)NS(=O)(=O)N(C)CC(OC)OC)cc3n2C1
null
null
null
1,518,109
ord_dataset-8c74302143c04eb9983e4b3a7ead2d72
null
2014-01-01T00:12:00
true
[F:1][C:2]1[CH:31]=[C:30]([N+:32]([O-])=O)[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[N:19]=[CH:18][C:17]([CH2:20][N:21]4[CH2:26][CH2:25][O:24][CH2:23][C:22]4=[O:27])=[CH:16][CH:15]=3)[S:13][C:6]=12.[NH4+].[Cl-]>CO.O.[Zn]>[NH2:32][C:30]1[CH:29]=[CH:28][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]3[CH:11]=[C:12]([C:14]4[N:19]=[CH:18][C:17]([CH2:20][N:21]5[CH2:26][CH2:25][O:24][CH2:23][C:22]5=[O:27])=[CH:16][CH:15]=4)[S:13][C:6]=23)=[C:2]([F:1])[CH:31]=1
O=C1COCCN1Cc1ccc(-c2cc3nccc(Oc4ccc([N+](=O)[O-])cc4F)c3s2)nc1
null
null
[Cl-]
[NH4+]
[Zn]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CO
O
null
null
null
null
null
null
null
null
null
null
null
To a suspension of 121 (135 mg, 0.281) in MeOH (10 mL) was added Zinc powder (184 mg, 2.81 mmol) and NH4Cl (60.1 mg, 1.124 mmol) in water (1 mL) and the reaction mixture was stirred at reflux for 5 hours then stirred at RT for 2 days. The mixture was filtered, concentrated, dissolved in DCM and MeOH and the resultant solution was then washed with water. The organic phase was collected, dried over anhydrous Na2SO4, filtered and concentrated. The resultant solid 122 (65 mg, 51% yield) was used directly in the next step with no additional purification. MS (m/z)=451.49 (M+H)
Nc1ccc(Oc2ccnc3cc(-c4ccc(CN5CCOCC5=O)cn4)sc23)c(F)c1
null
51.4
null
1,622,164
ord_dataset-35c51552812941cda45194a013d34bb9
null
2015-01-01T00:08:00
true
C(OC([NH:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20]([C:22]3[S:23][CH:24]=[CH:25][CH:26]=3)[C:19]3[C:27](=[O:37])[N:28](C(OC(C)(C)C)=O)[CH2:29][C:18]=3[C:17]=2[F:38])[CH2:13][CH2:12][O:11][CH2:10]1)=O)(C)(C)C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20]([C:22]3[S:23][CH:24]=[CH:25][CH:26]=3)[C:19]3[C:27](=[O:37])[NH:28][CH2:29][C:18]=3[C:17]=2[F:38])[CH2:13][CH2:12][O:11][CH2:10]1
CC(C)(C)OC(=O)N[C@H]1COCC[C@H]1Nc1nc(-c2cccs2)c2c(c1F)CN(C(=O)OC(C)(C)C)C2=O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
ClCCl
O=C(O)C(F)(F)F
null
null
null
null
null
null
null
null
null
null
null
A solution of tert-butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-7-fluoro-3-oxo-4-(thiophen-2-yl)-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (30 mg, 0.055 mmol) in TFA/DCM (1:1, 10 mL) was stirred at RT for 2 h. The solvent was removed and the resulting crude material was reconstituted in MeOH/DCM (20 mL) and purified via preparative HPLC. The collected fractions were combined and stripped to dryness via rotary evaporation to yield the title compound (16 mg, 85%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.79 (d, J=9.76 Hz, 1 H), 2.12 (qd, J=12.94, 5.13 Hz, 1 H), 3.56-3.68 (m, 1 H), 3.75 (d, J=11.72 Hz, 1 H), 3.89 (br s, 1 H), 4.02 (d, J=11.72 Hz, 2 H), 4.28-4.37 (m, 1 H), 4.38-4.49 (m, 2 H), 7.10-7.20 (m, 1 H), 7.28 (d, J=4.88 Hz, 1 H), 7.59-7.70 (m, 1 H), 7.93 (br s, 2 H), 8.52 (s, 1 H), 9.02 (dd, J=3.91, 0.98 Hz, 1 H). [M+H] calc'd for C16H17FN4O2S, 349; found, 349.
N[C@H]1COCC[C@H]1Nc1nc(-c2cccs2)c2c(c1F)CNC2=O
null
83.5
null
1,292,705
ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c
null
2013-01-01T00:05:00
true
[ClH:1].[CH3:2][N:3]1[CH2:8][CH2:7][CH:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15](=[O:32])[CH2:16][O:17][CH2:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][N:20]3C(OC(C)(C)C)=O)[CH2:11][CH2:10]2)[CH2:5][CH2:4]1>C(OCC)(=O)C.C(OCC)C>[ClH:1].[ClH:1].[ClH:1].[CH3:2][N:3]1[CH2:4][CH2:5][CH:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15](=[O:32])[CH2:16][O:17][CH2:18][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][NH:20]3)[CH2:11][CH2:10]2)[CH2:7][CH2:8]1
CN1CCC(N2CCN(C(=O)COCC3CCCCN3C(=O)OC(C)(C)C)CC2)CC1
null
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCOCC
CCOC(C)=O
null
null
null
null
null
null
null
null
null
45
2
Hydrogen chloride (26.0 ml, 52.10 mmol, 2 M solution in diethyl ether) was added at room temperature to a solution of tert-butyl 2-((2-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)-2-oxoethoxy)methyl)piperidine-1-carboxylate (4.57 g, 10.42 mmol) in a mixture of ethyl acetate (15 ml) and diethyl ether (50 ml). The reaction mixture was stirred for 2 h at 45° C. Then the resulting white solid was filtered off and dried.
CN1CCC(N2CCN(C(=O)COCC3CCCCN3)CC2)CC1
null
null
null
889,218
ord_dataset-d728a2f811c0424cbcdb5a84d02b93ae
null
2009-01-01T00:06:00
true
Cl.[Cl:2][C:3]1[C:8]([C:9](Cl)=[O:10])=[CH:7][N:6]=[CH:5][CH:4]=1.[CH3:12][NH2:13]>C1COCC1>[Cl:2][C:3]1[CH:4]=[CH:5][N:6]=[CH:7][C:8]=1[C:9]([NH:13][CH3:12])=[O:10]
O=C(Cl)c1cnccc1Cl
CN
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1CCOC1
null
null
null
null
null
null
null
null
null
null
25
1
To a suspension of crude 4-chloronicotinoyl chloride hydrochloride in 25 mL of THF was added methylamine solution (2M in THF, 20 mL, 40 mmol, 4.0 eq) at 0° C. The reaction mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure. The crude material was dissolved in ethylacetate (75 mL) and water/brine/saturated sodium bicarbonate solution (1/1/1, 75 mL). The separated aqueous layer was extracted with EtOAc. The combined organic layers were washed with water/brine/saturated sodium bicarbonate solution (1/1/1, 25 mL) and brine (25 mL) and dried over sodium sulfate. Removal of the solvent under reduced pressure afforded the title compound as orange solid (400 mg, 24%), which was used without further purification. MH+=171.0, Rt=0.55 min.
CNC(=O)c1cnccc1Cl
null
24
null
712,690
ord_dataset-c8a367b56b4f406b878f51867b157d19
null
2006-01-01T00:06:00
true
[O:1]=[C:2]1[C:10](=[C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]([CH2:20][C:21]([OH:23])=[O:22])[O:12]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1.C[O-].[Na+:26].CO.CCOC(C)=O>CO>[O:1]=[C:2]1[NH:3][C:4]2[C:9](/[C:10]/1=[C:11]1\[O:12][CH:13]([CH2:20][C:21]([O-:23])=[O:22])[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]\1=3)=[CH:8][CH:7]=[CH:6][CH:5]=2.[Na+:26]
O=C(O)CC1OC(=C2C(=O)Nc3ccccc32)c2ccccc21
null
null
C[O-]
[Na+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCOC(C)=O
CO
null
null
null
null
null
null
null
null
null
null
0.25
To a slurry of [3-(2-oxo-1,2-dihydro-indol-3-ylidene)-1,3-dihydro-isobenzofuran-1-yl]-acetic acid (430 mg, 1.40 mmol) in MeOH (100.0 ml) at room temperature was added 0.5M NaOMe/MeOH (2.80 ml). The solution was rapidly stirred for 15 minutes and then rotary evaporated (combined 116 mg of product obtained from previously run reaction). The solid was chased with MeOH (20 ml), and then with EtOAc (2×15 ml) to give sodium [(3E)-3-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)-1,3-dihydro-2-benzofuran-1-yl]acetate as a yellow solid (576 mg, 100%).
O=C([O-])CC1O/C(=C2/C(=O)Nc3ccccc32)c2ccccc21
null
100
null
181,337
ord_dataset-2841bde0239a4964a69f490c014a6e43
null
1988-01-01T00:12:00
true
C(OC(N=NC(OCC)=O)=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:32][C:33]([F:43])([F:42])[C:34]1[CH:41]=[CH:40][CH:39]=[CH:38][C:35]=1[CH2:36]O.[NH:44]=[N+:45]=[N-:46]>C1(C)C=CC=CC=1>[F:32][C:33]([F:43])([F:42])[C:34]1[CH:41]=[CH:40][CH:39]=[CH:38][C:35]=1[CH2:36][N:44]=[N+:45]=[N-:46]
[N-]=[N+]=N
OCc1ccccc1C(F)(F)F
null
CCOC(=O)N=NC(=O)OCC
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
Cc1ccccc1
null
null
null
null
null
null
null
null
null
null
25
2
First a solution of 17.4 g (0.1 mol) of azodicarboxylic acid diethyl ester in 50 ml of toluene is added dropwise at 10°-20° to a solution of 26.2 g (0.1 mol) of triphenylphosphine in 260 ml of toluene and then, at 5°-10°, a solution of 17.6 g (0.1 mol) of o-trifluoromethylbenzyl alcohol in 120 ml of a 1N solution of hydrazoic acid in toluene is added dropwise thereto and the whole is stirred at room temperature for 2 hours. The precipitated hydrazinodicarboxylic acid ester is filtered off with suction, the toluene solution is concentrated by evaporation and the residue is treated with cyclohexane. The cyclohexane solution is decanted off from the insoluble portions, filtered through a small amount of silica gel and concentrated by evaporation at 50° in vacuo. In this manner o-trifluoromethylbenzyl azide is obtained in the form of a colourless liquid.
[N-]=[N+]=NCc1ccccc1C(F)(F)F
null
null
null
655,158
ord_dataset-fe016e2f90e741a590ad77fd5933161f
null
2004-01-01T00:11:00
true
C[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([N:11]([S:13]([C:16]2[CH:21]=[CH:20][C:19](F)=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH3:12])[C:3]=1[CH3:23].[OH:24][CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([C:32]1[O:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[CH:36]=1)=[O:31]>>[O:33]1[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[CH:36]=[C:32]1[C:30]([NH:29][CH2:28][CH2:27][CH2:26][CH2:25][O:24][C:19]1[CH:18]=[CH:17][C:16]([S:13]([N:11]([CH3:12])[C:4]2[C:3]([CH3:23])=[CH:2][CH:10]=[CH:9][C:5]=2[C:6]([OH:8])=[O:7])(=[O:14])=[O:15])=[CH:21][CH:20]=1)=[O:31]
O=C(NCCCCO)c1cc2ccccc2o1
Cc1ccc(C(=O)O)c(N(C)S(=O)(=O)c2ccc(F)cc2)c1C
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
The product of Example 2 (0.40 g, 1.24 mmol) was coupled to N-(4-hydroxybutyl)-1-benzofuran-2-carboxamide, prepared according to Example 17, (0.29 g, 1.24 mmol) using the procedure of Example 3 to provide 0.34 g (51% yield) of an off white powder. MP>200° C.; 1H NMR (DMSO-d6): δ 1.35-1.62 (m, CH2, CH2), 1.9 (s, CH3), 3.20 (s, CH3), 3.32-3.41 (m, CH2, CH2), 7.0-7.1 (m, 4 Ar H), 7.35 (t, 1 Ar H), 7.45 (t, 1 Ar H), 7.54 (s, 1 Ar H), 7.65 (d, 1 Ar H), 7.77 (d, 1 Ar H), 7.92 (m, 3 Ar H) 8.8 (t, NH), Electrospray Mass Spec: m/z 537.2 (M+H)+.
Cc1cccc(C(=O)O)c1N(C)S(=O)(=O)c1ccc(OCCCCNC(=O)c2cc3ccccc3o2)cc1
null
51
null
781,787
ord_dataset-8034115bd2ec4d3e95bd3ff7cfde0bde
null
2007-01-01T00:07:00
true
C(OC([N:8]1[CH2:24][CH2:23][N:11]2[C:12](=[O:22])[C:13]3[C:18]([C@@H:10]2[CH2:9]1)=[CH:17][C:16]([O:19][CH3:20])=[CH:15][C:14]=3[Cl:21])=O)(C)(C)C.Cl>>[ClH:21].[Cl:21][C:14]1[CH:15]=[C:16]([O:19][CH3:20])[CH:17]=[C:18]2[C:13]=1[C:12](=[O:22])[N:11]1[CH2:23][CH2:24][NH:8][CH2:9][C@H:10]12
COc1cc(Cl)c2c(c1)[C@@H]1CN(C(=O)OC(C)(C)C)CCN1C2=O
null
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
0.02
To N-(t-butoxycarbonyl)-(R)-1,3,4,10b-tetrahydro-7-chloro-9-methoxy-pyrazino[2,1-a]isoindol-6(2H)-one (16 mg, 0.05 mmol) was added concentrated aqueous hydrochloric acid (1 mL, 12N). After 1 min, the solution was concentrated, diluted with water, and lyopholized to give a white solid (13 mg, quant). MS (ESI) 253.2, 255.2 (M−Cl).
COc1cc(Cl)c2c(c1)[C@@H]1CNCCN1C2=O
null
null
null
219,964
ord_dataset-6cb04513a4a244c0b612b566096f4b3d
null
1990-01-01T00:12:00
true
[OH:1][CH2:2][CH2:3][NH:4][C:5](=[O:18])[C:6]([F:17])([F:16])[CH2:7][C:8]1[N:9]=[C:10]([N+:13]([O-:15])=[O:14])[NH:11][CH:12]=1.N1C=CC=CC=1.Cl[C:26]([O:28][CH3:29])=[O:27]>C(Cl)(Cl)Cl>[N+:13]([C:10]1[NH:11][CH:12]=[C:8]([CH2:7][C:6]([F:17])([F:16])[C:5]([NH:4][CH2:3][CH2:2][O:1][C:26]([O:28][CH3:29])=[O:27])=[O:18])[N:9]=1)([O-:15])=[O:14]
O=C(NCCO)C(F)(F)Cc1c[nH]c([N+](=O)[O-])n1
COC(=O)Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
ClC(Cl)Cl
c1ccncc1
null
null
null
null
null
null
null
null
null
null
null
3-(2'-Nitroimidazolyl)-2,2-difluoropropionic acid hydroxyethylamide (6.0 g, 22.7 mmol) was dissolved in a solvent mixture of methyl chloroformate (30 ml) and chloroform (30 ml) and cooled by ice. To the solution, a solution of pyridine (6.0 ml) in chloroform (30 ml) was dropwise added over 2 hours. The completion of the reaction was confirmed by thin-layer chromatography. Then, the reaction solution was washed with dilute hydrochloric acid and water, dried over magnesium sulfate, concentrated and subjected to silica gel column chromatography to obtain methyl 3-(2'-nitroimidazolyl)-2,2-difluoropropionamidoethoxyformate (6.89 g). m.p. 50.5°-52.5° C.
COC(=O)OCCNC(=O)C(F)(F)Cc1c[nH]c([N+](=O)[O-])n1
null
null
null
694,200
ord_dataset-a7baa616c65d42559e25ca0ba61e0744
null
2006-01-01T00:01:00
true
C([O:3][C:4](=[O:31])[C:5]([CH3:30])([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]2[N:18]=[C:19]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[O:20][C:21]=2[CH3:22])=[CH:10][C:9]=1[CH3:29])[CH3:6])C.[OH-].[Na+]>C1COCC1.CO>[CH3:30][C:5]([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]2[N:18]=[C:19]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[O:20][C:21]=2[CH3:22])=[CH:10][C:9]=1[CH3:29])([CH3:6])[C:4]([OH:31])=[O:3]
CCOC(=O)C(C)(C)Oc1ccc(OCCc2nc(-c3ccccc3)oc2C)cc1C
null
null
[Na+]
[OH-]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CO
C1CCOC1
null
null
null
null
null
null
null
null
null
55
null
A solution of 2-methyl-2-{2-methyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}propionic acid ethyl ester (5.00 g, 11.8 mmol) in THF (30 mL) and MeOH (60 mL) was treated with 5N aqueous NaOH (20 mL). The solution was heated at 55° C. for 1 h, cooled to ambient temperature, and concentrated in vacuo. The residue was treated with ice water (20 mL), acidified with 5N aqueous HCl (25 mL), and extracted with ethyl acetate (200 mL). The organic layer was washed with brine (40 mL), dried (Na2SO4), and concentrated to a white solid (4.46 g, 96%): mp 117° C.; 1H NMR (400 MHz, CDCl3) δ 1.53 (s, 6H), 2.19 (s, 3H), 2.38 (s, 3H), 2.98 (t, 2H, J=6.6 Hz), 4.15 (t, 2H, J=6.6 Hz), 6.58 (dd, 1H, J=3.4, 8.8 Hz), 6.70 (d, 1H, J=2.9 Hz), 6.80 (d, 1H, J=8.8 Hz), 7.38-7.45 (m, 3H), 7.97-8.00 (m, 2H); MS (FIA) m/e 394.2 [M−1].
Cc1cc(OCCc2nc(-c3ccccc3)oc2C)ccc1OC(C)(C)C(=O)O
null
null
null
1,156,323
ord_dataset-b195433d5c354ddfb6cde0d53c41910f
null
2012-01-01T00:04:00
true
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15]O)=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)[Cl:37]>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][Cl:37])=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
OCc1ccc(OCc2ccccc2)cn1
ClC(Cl)(Cl)Cl
null
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
25
null
To a carbon tetrachloride (10 mL) solution of (5-benzyloxy-pyridin-2-yl)-methanol (500 mg) described in Manufacturing Example 127-1-2 was added triphenylphosphine (791 mg), which was refluxed for 19 hours and 35 minutes under nitrogen atmosphere. The reaction mixture was cooled to room temperature and then concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=3:1) to obtain the title compound (386 mg).
ClCc1ccc(OCc2ccccc2)cn1
null
null
null
219,926
ord_dataset-6cb04513a4a244c0b612b566096f4b3d
null
1990-01-01T00:12:00
true
[Cl:1][C:2]1[C:7]([CH2:8]Br)=[C:6]([Cl:10])[C:5]([Cl:11])=[C:4]([Cl:12])[C:3]=1[Cl:13].[OH2:14]>CN(C=O)C>[Cl:1][C:2]1[C:7]([CH2:8][OH:14])=[C:6]([Cl:10])[C:5]([Cl:11])=[C:4]([Cl:12])[C:3]=1[Cl:13]
Clc1c(Cl)c(Cl)c(CBr)c(Cl)c1Cl
O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CN(C)C=O
null
null
null
null
null
null
null
null
null
null
null
null
A solution of 20.7 g of pentachlorobenzyl bromide in 300 ml DMF containing 30 ml of water was heated at reflux for two hours. On dilution with water solids precipitated. The solid was filtered out and washed on the filter until the wash water was free of bromide ions. On drying, 15.2 g of pentachlorobenzyl alcohol of m.p. 193°-195° C. were obtained.
OCc1c(Cl)c(Cl)c(Cl)c(Cl)c1Cl
null
null
null
512,260
ord_dataset-85c00026681b46f89ef8634d2b8618c3
null
2001-01-01T00:07:00
true
[CH:1]([C:4]1[C:12]([C:13](=[O:26])[CH:14]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:15][C:16]([O:18]C)=[O:17])=[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][N:6]2[N:5]=1)([CH3:3])[CH3:2].C(O)C.[OH-].[Na+].Cl>O>[CH:1]([C:4]1[C:12]([C:13](=[O:26])[CH:14]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:15][C:16]([OH:18])=[O:17])=[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][N:6]2[N:5]=1)([CH3:3])[CH3:2]
COC(=O)CC(C(=O)c1c(C(C)C)nn2ccccc12)c1ccccc1
null
null
Cl
[Na+]
[OH-]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCO
O
null
null
null
null
null
null
null
null
null
25
1
The compound (1.58 g) of Example 25 was dissolved into ethanol (15 ml), and, after adding IN aqueous solution of sodium hydroxide (5 ml), the mixture was stirred for 1 hour at room temperature. water was added to the reaction liquor, then 10% hydrochloric acid was added to make pH 3, which was extracted with methylene chloride. After the organic layer was dried over anhydrous sodium sulfate, solvent was distilled off under reduced pressure to obtain aimed product (1.50 g) as colorless powder.
CC(C)c1nn2ccccc2c1C(=O)C(CC(=O)O)c1ccccc1
null
98.9
null
413,352
ord_dataset-275344fd078b4340b89ca0b6e92beb95
null
1998-01-01T00:10:00
true
[Cl:1][C:2]1[C:6]([S:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:8])=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[NH:4][C:3]=1[C:22]([F:25])([F:24])[F:23].[OH:26]O>C(O)(=O)C>[Cl:1][C:2]1[C:6]([S:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)(=[O:26])=[O:8])=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[NH:4][C:3]=1[C:22]([F:24])([F:23])[F:25]
O=S(c1ccccc1)c1c(-c2ccc(Cl)cc2)[nH]c(C(F)(F)F)c1Cl
OO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CC(=O)O
null
null
null
null
null
null
null
null
null
null
50
7
A mixture of 3-chloro-5-(p-chlorophenyl)-4-(phenylsulfinyl)-2-(trifluoromethyl)pyrrole (0.335 g, 0.83 mmol) and 30% hydrogen peroxide solution (0.28 mL, 2.49 mmol) in acetic acid is stirred at 50° C. for 7 hours, cooled and poured into an ice-water mixture. The resultant aqueous mixture is filtered to obtain a solid which is washed with water and dried to give the title product as a colorless solid (mp 158°-161° C.).
O=S(=O)(c1ccccc1)c1c(-c2ccc(Cl)cc2)[nH]c(C(F)(F)F)c1Cl
null
null
null
649,780
ord_dataset-271c0b74f4794a06992957029b3151ba
null
2004-01-01T00:10:00
true
[OH-].[Na+].Cl[S:4]([C:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[S:9][CH:8]=1)(=[O:6])=[O:5].[NH:16]([CH2:18][C:19]([OH:21])=[O:20])[CH3:17].C1(C)C=CC=CC=1>O>[S:9]1[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:7]([S:4]([N:16]([CH2:18][C:19]([OH:21])=[O:20])[CH3:17])(=[O:6])=[O:5])=[CH:8]1
CNCC(=O)O
O=S(=O)(Cl)c1csc2ccccc12
null
[Na+]
[OH-]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
O
Cc1ccccc1
null
null
null
null
null
null
null
null
null
60
6.5
6 g of NaOH, 23.27 g of 3-chlorosulphonyl-benzothiophene and 13.36 g of sarcosine are added to a mixture of 200 ml of toluene and 200 ml of water and stirred for 6.5 hours at 60° C. For working up, the aqueous phase is separated off and the organic phase is extracted with 100 ml of 2 N NaOH solution. The combined aqueous phases are acidified with conc. HCl and then extracted twice with 300 ml of ethyl acetate. After washing with saturated aqueous saline solution and drying over magnesium sulphate the organic phase is concentrated by evaporation. The crude product obtained is recrystallised from 100 ml of dichloroethane. Yield: 13.14 g. M.p.: 139-140° C.
CN(CC(=O)O)S(=O)(=O)c1csc2ccccc12
null
null
null
542,126
ord_dataset-49124ff635234889bd8dcfe87f4f9013
null
2002-01-01T00:04:00
true
[NH2:1][C:2]1[O:6][N:5]=[C:4]([C:7]([CH3:10])([CH3:9])[CH3:8])[C:3]=1[Br:11].[C:12]1([S:18](Cl)(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>N1C=CC=CC=1.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[C:12]1([S:18]([N:1]([C:2]2[O:6][N:5]=[C:4]([C:7]([CH3:8])([CH3:10])[CH3:9])[C:3]=2[Br:11])[S:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)(=[O:20])=[O:19])(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
CC(C)(C)c1noc(N)c1Br
O=S(=O)(Cl)c1ccccc1
null
CN(C)c1ccncc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
c1ccncc1
CCOC(C)=O
null
null
null
null
null
null
null
null
null
50
16
5-Amino-4-bromo-3-tert-butylisoxazole (440 mg, 2.0 mmol) was dissolved in dry pyridine (2 ml). Benzenesulfonyl chloride (344 mg, 2.0 mmol) and 4-dimethylamino-pyridine (5 mg) was added and the reaction was stirred at 50° C. for 16 h. The reaction mixture was diluted with ethyl acetate (20 ml), washed with 1N HCl (2×10 ml) and the organic phase was dried over magnesium sulfate. The solvent was removed under reduced pressure to yield a crude product, which was recrystallized from ethyl acetate/hexanes to give 300 mg (60% yield) of N-benzenesulfonyl-N-(4-bromo-3-tert-butyl-5-isoxazolyl)benzenesulfonamide.
CC(C)(C)c1noc(N(S(=O)(=O)c2ccccc2)S(=O)(=O)c2ccccc2)c1Br
null
60.1
null
510,734
ord_dataset-85c00026681b46f89ef8634d2b8618c3
null
2001-01-01T00:07:00
true
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([CH2:14][CH3:15])=[N:10][NH:11]2)=[CH:7][CH:6]=1)=[O:4].[CH:16]1(Br)[CH2:19][CH2:18][CH2:17]1>>[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([CH2:14][CH3:15])=[N:10][N:11]2[CH:16]2[CH2:19][CH2:18][CH2:17]2)=[CH:7][CH:6]=1)=[O:4]
BrC1CCC1
CCc1n[nH]c2cc(C(=O)OC)ccc12
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
This compound was prepared according to the method of Preparation 3, using 750 mg (3.67 mmol, 1.0 equiv) 3-ethyl-1H-indazole-6-carboxylic acid methyl ester and 0.38 mL (4.04 mmol, 1.1 equiv) cyclobutyl bromide as starting materials to give 307 mg (32%) of a clear oil: HRMS calcd for C15H18N2O2+H: 259.1447. Found: 259.14550.
CCc1nn(C2CCC2)c2cc(C(=O)OC)ccc12
null
32.4
null
800,295
ord_dataset-56a22bc0c3b14f87b9aa3f2fc6488ee7
null
2007-01-01T00:12:00
true
C([NH:18][C@H:19]([C:25]([C@@:27]1([N:36]2[C:46]3[N:45]=[C:43]([NH2:44])[NH:42][C:40](=[O:41])[C:39]=3[N:38]=[CH:37]2)[O:35][C@H:32]([CH2:33][OH:34])[C@@H:30]([OH:31])[C@H:28]1[OH:29])=[O:26])[CH2:20][CH2:21][CH2:22][CH2:23][NH2:24])(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O.N1CCCCC1>N1C=CC=CC=1>[NH2:18][C@H:19]([C:25]([C@@:27]1([N:36]2[C:46]3[N:45]=[C:43]([NH2:44])[NH:42][C:40](=[O:41])[C:39]=3[N:38]=[CH:37]2)[O:35][C@H:32]([CH2:33][OH:34])[C@@H:30]([OH:31])[C@H:28]1[OH:29])=[O:26])[CH2:20][CH2:21][CH2:22][CH2:23][NH2:24]
NCCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)[C@@]1(n2cnc3c(=O)[nH]c(N)nc32)O[C@H](CO)[C@@H](O)[C@H]1O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
c1ccncc1
C1CCNCC1
null
null
null
null
null
null
null
null
null
0
5
To a stirred solution of 800 mg of (Nα-FMOC-lysyl)guanosine in anhydrous pyridine was added anhydrous piperidine (4 mol eq.). The mixture was allowed to stir for 5 hr at 0° C. and then was evaporated to dryness. The residue was dissolved in DMF and purified by slow addition of the DMF solution to a rapidly stirred solution of EtOH—Et2O, yielding a precipitate.
NCCCC[C@H](N)C(=O)[C@@]1(n2cnc3c(=O)[nH]c(N)nc32)O[C@H](CO)[C@@H](O)[C@H]1O
null
null
null
238,406
ord_dataset-960c6b9c4fc74afd90a3ebf713215626
null
1991-01-01T00:12:00
true
[CH2:1]([C:7]1[CH:8]=[CH:9][C:10]2[CH:15]([C:16]([O:18]CC)=[O:17])[S:14][CH2:13][C:12](=[O:21])[C:11]=2[CH:22]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[OH-].[K+]>CO.O>[CH2:1]([C:7]1[CH:8]=[CH:9][C:10]2[CH:15]([C:16]([OH:18])=[O:17])[S:14][CH2:13][C:12](=[O:21])[C:11]=2[CH:22]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
CCCCCCc1ccc2c(c1)C(=O)CSC2C(=O)OCC
null
null
[K+]
[OH-]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
O
CO
null
null
null
null
null
null
null
null
null
25
1
In methanol (150 ml) was suspended ethyl 6-hexyl-3,4-dihydro-1H-2-benzothiopyran-4-one-1-carboxylate (41 g) followed by addition of 2N-KOH (150 ml). The mixture was stirred at room temperature for one hour. The reaction mixture was poured in water, acidified and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4) and the solvent was distilled off to give 6-hexyl-3,4-dihydro-1H-2-benzothiopyran-4-one-1-carboxylic acid (27.5 g, yield 74%). Recrystallization from ether-hexane gave colorless plates.
CCCCCCc1ccc2c(c1)C(=O)CSC2C(=O)O
null
73.5
null
140,824
ord_dataset-a2a0fbbcd49a46ffaa432d7ceae8a506
null
1986-01-01T00:02:00
true
C([O:4][C:5]1[C:6]([CH3:37])=[C:7]2[C:12](=[C:13]([O:17][CH3:18])[C:14]=1[O:15][CH3:16])[O:11][C:10]([CH2:20][CH2:21][O:22][C:23]1[CH:36]=[CH:35][C:26]([CH2:27][CH:28]3[S:32][C:31](=N)[NH:30][C:29]3=[O:34])=[CH:25][CH:24]=1)([CH3:19])[CH2:9][CH2:8]2)(=O)C.Cl.[OH2:39]>COCCO>[OH:4][C:5]1[C:6]([CH3:37])=[C:7]2[C:12](=[C:13]([O:17][CH3:18])[C:14]=1[O:15][CH3:16])[O:11][C:10]([CH2:20][CH2:21][O:22][C:23]1[CH:24]=[CH:25][C:26]([CH2:27][CH:28]3[S:32][C:31](=[O:39])[NH:30][C:29]3=[O:34])=[CH:35][CH:36]=1)([CH3:19])[CH2:9][CH2:8]2
COc1c(OC(C)=O)c(C)c2c(c1OC)OC(C)(CCOc1ccc(CC3SC(=N)NC3=O)cc1)CC2
O
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
COCCO
null
null
null
null
null
null
null
null
null
null
null
null
560 mg of 5-{4-[2-(6-acetoxy-7,8-dimethoxy-2,5-dimethylchroman-2-yl)ethoxy]benzyl}-2-iminothiazolidin-4-one (prepared as described in Example 7) were added to a mixture of 7 ml of concentrated hydrochloric acid, 2.5 ml of water and 10 ml of ethylene glycol monomethyl ether, and the mixture was heated under reflux for 13 hours. The reaction mixture was then processed and purified as described in Example 1(a), except that the crude product, in the form of an oil, was purified by column chromatography through silica gel eluted with a 9:1 by volume mixture of chloroform and ethyl acetate, to give the title compound.
COc1c(O)c(C)c2c(c1OC)OC(C)(CCOc1ccc(CC3SC(=O)NC3=O)cc1)CC2
null
null
null
967,184
ord_dataset-03ba810b7f464a06b5d8787af2e8b64e
null
2010-01-01T00:06:00
true
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[C:9]([C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1)([O:11][CH2:12][CH3:13])=[O:10]>>[CH2:12]([O:11][C:9](=[O:10])[C:14]1[CH:15]=[CH:16][CH:17]=[C:18]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH:19]=1)[CH3:13]
Clc1ccnc(Cl)n1
CCOC(=O)c1cccc(B(O)O)c1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
2,4 dichloropyrimidine was coupled to 3-carboethoxyphenylboronic acid following procedure A. LC-MS showed the product to be >95% pure and to have the expected M+H+ of 195.
CCOC(=O)c1cccc(-c2ccnc(Cl)n2)c1
null
null
null
1,758,120
ord_dataset-97eb2ab57fec4160922caae33b54d956
null
2016-01-01T00:08:00
true
[C:1]1([CH2:7][CH2:8][C:9](=O)[CH3:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si](C)(C)[O:14][SiH](C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][OH:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
C[SiH](C)O[Si](C)(C)C
CC(=O)CCc1ccccc1
null
CCCC[N+](CCCC)(CCCC)CCCC
[F-]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1CCOC1
null
null
null
null
null
null
null
null
null
null
25
24
A 30-mL eggplant flask equipped with a magnetic stirrer was heat dried while pumping to a vacuum of 5 Pa before its interior was purged with nitrogen atmosphere. To the flask, 4-phenyl-2-butanone (148 mg, 1.0 mol) and 1,1,1,3,3-pentamethyldisiloxane (371 mg, 2.5 mmol) were added through a syringe, and iron complex A (5.0 mg, 0.01 mmol) was added as catalyst. The solution was stirred at room temperature for 24 hours. At 0° C., THF (1 mL) and tetrabutylammonium fluoride in THF (1 M, 1 mL) were then added to the solution, which was stirred at 0° C. for 1 hour. The solvent was distilled off in vacuum. The crude product was purified by silica gel-packed column chromatography using hexane/ethyl acetate (3/1) as developing solvent, obtaining 4-phenyl-1-butanol (139 mg, 0.92 mmol, 92%). The results are shown as Entry 2 in Table 7. The resulting alcohol was identified for geometry by 1H and 13C-NMR spectroscopy.
OCCCCc1ccccc1
null
36.8
null
1,114,116
ord_dataset-4226e9b4f9f845db967ed997270dcafc
null
2011-01-01T00:12:00
true
[CH2:1]([O:8][C:9]([N:11]1[C@@H:15]([CH2:16][CH:17]=O)[CH2:14][O:13][C:12]1([CH3:20])[CH3:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:22]1[C:24]2([CH2:29][CH2:28][NH:27][CH2:26][C@H:25]2[OH:30])[CH2:23]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH2:1]([O:8][C:9]([N:11]1[C@@H:15]([CH2:16][CH2:17][N:27]2[CH2:28][CH2:29][C:24]3([CH2:22][CH2:23]3)[C@H:25]([OH:30])[CH2:26]2)[CH2:14][O:13][C:12]1([CH3:20])[CH3:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
O[C@@H]1CNCCC12CC2
CC1(C)OC[C@H](CC=O)N1C(=O)OCc1ccccc1
null
CC(=O)O[BH-](OC(C)=O)OC(C)=O
Cl
[Na+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCN(CC)CC
ClCCl
null
null
null
null
null
null
null
null
null
null
null
To a solution of (S)-2,2-dimethyl-4-(2-oxo-ethyl)-oxazolidine-3-carboxylic acid benzyl ester (8.51 g, 30.7 mmol) in dichloromethane (140 mL) were added (S)-6-aza-spiro[2.5]octan-4-ol hydrochloride (intermediate 2; 5.03 g, 30.7 mmol), triethylamine (3.11 g, 30.7 mmol) and sodium triacetoxyborohydride (9.11 g, 43.0 mmol) at room temperature. After 1 h the reaction mixture was partitioned between sat. aq. sodium hydrogencarbonate solution and dichloromethane. The aqueous layer was extracted twice with dichloromethane, the combined organic phases were dried (MgSO4), filtered, and evaporated to afford the title compound (11.6 g, 97%). Light yellow gum, MS (ISP)=389.3 (M+H)+.
CC1(C)OC[C@H](CCN2CCC3(CC3)[C@H](O)C2)N1C(=O)OCc1ccccc1
null
97.3
null
1,227,600
ord_dataset-cde802cdb7434a5f82a22981ccaefc4e
null
2012-01-01T00:11:00
true
[CH2:1]([N:8]([CH2:12][C:13]1[C:18](Cl)=[N:17][C:16]([N:20]([CH3:24])[CH2:21][CH2:22][CH3:23])=[CH:15][N:14]=1)[CH2:9][CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].O>CN(C=O)C>[CH2:1]([N:8]1[CH2:12][C:13]2[N:14]=[CH:15][C:16]([N:20]([CH3:24])[CH2:21][CH2:22][CH3:23])=[N:17][C:18]=2[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
CCCN(C)c1cnc(CN(CCO)Cc2ccccc2)c(Cl)n1
null
null
CC(C)(C)[O-]
[K+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
O
CN(C)C=O
null
null
null
null
null
null
null
null
null
null
6
To a solution of 2-[benzyl({3-chloro-5-[methyl(propyl)amino]pyrazin-2-yl}methyl)amino]ethanol (0.75 g) in DMF (4 mL) was added potassium tert-butoxide (0.29 g) at 0° C., and the mixture was stirred for 6 hr. Water (10 mL) was added, and the mixture was extracted with ethyl acetate. The aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (solvent gradient: 10→50% ethyl acetate/hexane) to give the title compound (50 mg, 8%) as a pale-yellow oil.
CCCN(C)c1cnc2c(n1)OCCN(Cc1ccccc1)C2
null
7.4
null
536,044
ord_dataset-1884c7bf3d544afdb8d17b5d41b90a27
null
2002-01-01T00:03:00
true
[CH:1]([C@@H:4]([NH2:7])[CH2:5]O)([CH3:3])[CH3:2].O=S(Cl)Cl.[CH3:12][C:13]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:14]=1[N:22]=[C:23]=[S:24]>>[CH3:12][C:13]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:14]=1[N:22]=[C:23]1[NH:7][C@H:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][S:24]1
CC(C)[C@@H](N)CO
Cc1cc([N+](=O)[O-])ccc1N=C=S
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
O=S(Cl)Cl
null
null
null
null
null
null
null
null
null
null
null
null
(1R)-1-Isopropyl-2-hydroxyethylamine was reacted with SOCl2 followed by 2-Methyl-4-nitrophenyl isothiocyanate according to Method C2a to give (4R)-2-(2-methyl-4-nitrophenylimino)-4-isopropyl-1,3-thiazolidine. The thiazolidine was reacted with isobutyl bromide according to Method D2a to afford (4R)-2-(2-methyl -4-nitrophenylimino)-4-isopropyl-3-isobutyl-1,3-thiazolidine.
Cc1cc([N+](=O)[O-])ccc1N=C1N[C@H](C(C)C)CS1
null
null
null
38,358
ord_dataset-b0ddd49dad024fc7a23ae6f474f9c52f
null
1978-01-01T00:03:00
true
[OH:1][C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[N:5]=[CH:4][C:3]=1[C:11]([O:13][CH2:14][CH3:15])=[O:12].C(=O)([O-])[O-].[K+].[K+].[CH2:22](I)[CH3:23].CN(C)C=O>CN(P(N(C)C)(N(C)C)=O)C>[CH2:22]([N:5]1[CH:4]=[C:3]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:2](=[O:1])[N:7]2[N:8]=[CH:9][N:10]=[C:6]12)[CH3:23]
CCI
CCOC(=O)c1cnc2ncnn2c1O
null
O=C([O-])[O-]
[K+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CN(C)P(=O)(N(C)C)N(C)C
CN(C)C=O
null
null
null
null
null
null
null
null
null
null
null
Ethyl 7-hydroxy-1,2,4-triazolo [1,5-a]pyrimidine-6-carboxylate (10.4g, 50mM), potassium carbonate (7.0g, 50mM), ethyl iodide (8.0ml, 15mM), dry dimethylformamide (80ml) and hexamethylphosphorotriamide (80ml) was heated at 80° C for 4 hours. The resulting mixture was evaporated in vacuo and water added (100ml). The solution was washed with ether (5 × 100ml) then extracted with ethyl acetate (10 × 100ml). The ethyl acetate extracts were dried over magnesium sulphate, filtered and evaporated in vacuo. The crystals were filtered off and recrystallised from ethyl acetate. 37.9% yield (4.47g); mpt 129° - 131° C. δ (CDCl3) 8.62 (1H,s) and 8.12 (1H,s), ##STR55## 4.47 (2H,q) and 4.38 (2H,q), (OCH2CH3 and NCH2CH3), 1.62 (3H,t) and 1.50 (3H,t), (OCH2CH3 and NCH2CH3); ν max (KBr) 3400 (broad) 1715, 1690, 1610, 1570, 1480, 1370, 1325, 1210, 1175, 790cm-1 ; λmax (EtOH) 209 (εm 12,400), 252 (εm 8,260) and 290 (εm 11,800)nm.
CCOC(=O)c1cn(CC)c2ncnn2c1=O
null
37.9
null
1,677
ord_dataset-a0eff6fe4b4143f284f0fc5ac503acad
null
1976-01-01T00:01:00
true
[OH:1][C:2]1[C:3]2[C:8]([C:9]3[CH:10]=[CH:11][C:12]([C:16]([O:18][CH2:19][CH2:20][CH2:21][N:22]([CH2:27][CH2:28][CH2:29][CH3:30])[CH2:23][CH2:24][CH2:25][CH3:26])=[O:17])=[CH:13][C:14]=3[CH:15]=1)=[CH:7][CH:6]=[C:5]([C:31]([O:33][CH2:34][CH2:35][CH2:36][N:37]([CH2:42][CH2:43][CH2:44][CH3:45])[CH2:38][CH2:39][CH2:40][CH3:41])=[O:32])[CH:4]=2.[N+](=[CH:48][CH3:49])=[N-].CCOCC>CO>[CH2:23]([N:22]([CH2:27][CH2:28][CH2:29][CH3:30])[CH2:21][CH2:20][CH2:19][O:18][C:16]([C:12]1[CH:11]=[CH:10][C:9]2[C:8]3[C:3](=[CH:4][C:5]([C:31]([O:33][CH2:34][CH2:35][CH2:36][N:37]([CH2:42][CH2:43][CH2:44][CH3:45])[CH2:38][CH2:39][CH2:40][CH3:41])=[O:32])=[CH:6][CH:7]=3)[C:2]([O:1][CH2:48][CH3:49])=[CH:15][C:14]=2[CH:13]=1)=[O:17])[CH2:24][CH2:25][CH3:26]
CC=[N+]=[N-]
CCCCN(CCCC)CCCOC(=O)c1ccc2c(c1)cc(O)c1cc(C(=O)OCCCN(CCCC)CCCC)ccc12
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CO
CCOCC
null
null
null
null
null
null
null
null
null
null
8
The corresponding 9-ethoxy derivative is prepared by reacting a solution of bis[3-(dibutylamino)propyl] 9-hydroxyphenanthrene-2,7-dicarboxylate in methanol with diazoethane by co-distillation with ether into the reaction mixture at -10° to 30°C. After standing overnight, the crude bis[3-(dibutylamino)propyl]9-ethoxyphenanthrene-2,7-dicarboxylate so obtained is converted to its dihydrochloride salt by the addition of ethereal hydrogen chloride.
CCCCN(CCCC)CCCOC(=O)c1ccc2c(c1)cc(OCC)c1cc(C(=O)OCCCN(CCCC)CCCC)ccc12
null
null
null
715,216
ord_dataset-c8a367b56b4f406b878f51867b157d19
null
2006-01-01T00:06:00
true
[CH3:1][O:2][CH2:3][C@H:4]([NH:7][C:8]1[C:13]([NH2:14])=[C:12]([C:15]2[C:16]([CH3:23])=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[N:11]=[CH:10][N:9]=1)[CH2:5][CH3:6].[C:24](OCC)(=[O:28])[C:25]([CH3:27])=O>C(O)C>[CH3:1][O:2][CH2:3][C@H:4]([N:7]1[C:8]2[N:9]=[CH:10][N:11]=[C:12]([C:15]3[C:16]([CH3:23])=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[C:13]=2[N:14]=[C:25]([CH3:27])[C:24]1=[O:28])[CH2:5][CH3:6]
CCOC(=O)C(C)=O
CC[C@H](COC)Nc1ncnc(-c2ccc(OC)nc2C)c1N
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCO
null
null
null
null
null
null
null
null
null
null
null
18
(R)-N4-(1-Methoxymethyl-propyl)-6-(6-methoxy-2-methyl-pyridin-3-yl)-pyrimidine-4,5-diamine (0.2 g, 0.63 mmol) was diluted in ethanol (7 ml) and ethyl pyruvate was added (0.70 ml, 6.3 mmol). The mixture was stirred for 18 hours at which time the solution was concentrated. After concentrating the solution the product was purified by reverse phase HPLC to yield 4.0 mg of (R)-8-(1-methoxymethyl-propyl)-4-(6-methoxy-2-methyl-pyridin-3-yl)-6-methyl-8H-pteridin-7-one (Example 651a). 1H NMR (300 MHz, CDCl3) δ ppm 8.93 (s, 1 H), 7.62 (d, J=8.42 Hz, 1 H), 6.64 (d, J=8.42 Hz, 1 H), 4.23 (m, 1H), 3.94 (s, 3 H), 3.68 (m, 2 H), 3.25 (s, 3 H), 2.45 (s, 3H), 2.34 (s, 3 H), 1.22 (m, 2H), 0.82 (t, J=7.51 Hz, 3 H). MS (EI) 370.3 [(M+H)+, 100].
CC[C@H](COC)n1c(=O)c(C)nc2c(-c3ccc(OC)nc3C)ncnc21
null
null
null
781,048
ord_dataset-8034115bd2ec4d3e95bd3ff7cfde0bde
null
2007-01-01T00:07:00
true
[CH2:1]([O:8][C:9]([N:11]1[CH2:17][CH:16]2[CH:18]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([NH2:25])[CH:20]=3)[CH:13]([CH2:14][CH2:15]2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26][S:27](Cl)(=[O:29])=[O:28].Cl>N1C=CC=CC=1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH:13]2[CH:18]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([NH:25][S:27]([CH3:26])(=[O:29])=[O:28])[CH:20]=3)[CH:16]([CH2:15][CH2:14]2)[CH2:17]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
CS(=O)(=O)Cl
Nc1cccc(C2C3CCC2CN(C(=O)OCc2ccccc2)C3)c1
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
c1ccncc1
null
null
null
null
null
null
null
null
null
null
0
1
8-(3-Amino-phenyl)-3-aza-bicyclo[3.2.1]octane-3-carboxylic acid benzyl ester (185 mg, 0.55 mmol) was dissolved in pyridine (3 mL), cooled to 0° C. then charged with methanesulfonylchloride (0.064 mL, 0.825 mmol) dropwise, causing a color change from yellow to bright orange. The reaction was warmed to room temperature and judged complete by APCI MS after 1 h. Following a 1N HCl quench (10 mL), the product was extracted with EtOAc (2×30 mL), washed with saturated aqueous NaHCO3 solution (1×30 mL), saturated aqueous NaCl solution (1×30 mL), dried over Na2SO4, filtered and concentrated to give an orange liquid (153 mg, 67%). (TLC 30% EtOAc/hexanes Rf 0.15); 1H NMR (400 MHz, CDCl3) δ 7.33–7.19 (m, 5H), 7.21 (t, J=7.9 Hz, 1H), 7.14 (s, 1H), 7.05 (d, J=7.9 Hz, 1H), 6.99 (d, J=7.9 Hz, 1H), 5.24 (s, 2H), 4.03 (d, J=12.5 Hz, 1H), 3.94 (d, J=12.6 Hz, 1H), 3.07 (d, J=12.5 Hz, 1H), 3.03 (d, J=12.5 Hz, 1H), 2.90 (s, 3H), 2.86 (s, 1H), 2.50 (br s, 1H), 2.44 (br s, 1H), 1.60 (m, 2H), 1.47 (m, 2H); APCI MS m/z 415.1 (M+1)+.
CS(=O)(=O)Nc1cccc(C2C3CCC2CN(C(=O)OCc2ccccc2)C3)c1
null
67.1
null
1,449,217
ord_dataset-a86112d52cd54525a5e36d41f18aced2
null
2014-01-01T00:07:00
true
[Cl:1][C:2]1[CH:7]=[C:6]([NH2:8])[C:5](/[CH:9]=[CH:10]/OCC)=[CH:4][N:3]=1.Cl>CO>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:9]=[CH:10][NH:8][C:6]=2[CH:7]=1
CCO/C=C/c1cnc(Cl)cc1N
null
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CO
null
null
null
null
null
null
null
null
null
null
75
21
To a solution of 2-chloro-5-[(E)-2-ethoxyvinyl]pyridin-4-amine (preparation 36b, 1.00 g, 5.30 mmol) in methanol (20 mL) was added concentrated hydrochloric acid (1.00 mL, 32.64 mmol) and the mixture was stirred at 75° C. for 21 h. The mixture was concentrated under reduced pressure, treated with a saturated aqueous solution of potassium carbonate and extracted with ethyl acetate. The organic layer was dried and evaporated to yield the title compound (0.76 g, 99%) as a beige solid.
Clc1cc2[nH]ccc2cn1
null
94
null
1,311,148
ord_dataset-2d6edb8ffd434003bb508360153bd9bb
null
2013-01-01T00:07:00
true
[CH2:1]([O:8][C:9]1[C:16]([F:17])=[CH:15][C:12]([CH:13]=O)=[CH:11][C:10]=1[F:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:19]([O:21][C:22]([C:24](=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH3:25])=[O:23])[CH3:20]>O1CCCC1>[CH2:1]([O:8][C:9]1[C:16]([F:17])=[CH:15][C:12](/[CH:13]=[C:24](\[CH3:25])/[C:22]([O:21][CH2:19][CH3:20])=[O:23])=[CH:11][C:10]=1[F:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
CCOC(=O)C(C)=P(c1ccccc1)(c1ccccc1)c1ccccc1
O=Cc1cc(F)c(OCc2ccccc2)c(F)c1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1CCOC1
null
null
null
null
null
null
null
null
null
null
null
null
A solution of 4-(benzyloxy)-3,5-difluorobenzaldehyde (7) (1.32 g, 5.34 mmol) and (1-ethoxycarbonylethylidene)triphenyl phosphorane (2.32 g, 6.41 mmol) in tetrahydrofuran (53 mL) was refluxed for 2 hours. The reaction was concentrated in vacuo and was purified by flash column chromatography (0-100% EtOAc in hexanes) to give (E)-ethyl 3-(4-(benzyloxy)-3,5-difluorophenyl)-2-methylacrylate (8).
CCOC(=O)/C(C)=C/c1cc(F)c(OCc2ccccc2)c(F)c1
null
null
null
1,667,286
ord_dataset-9cc455db05a444779921f786a45b21a6
null
2015-01-01T00:12:00
true
Br[C:2]1[C:3]([O:23][CH3:24])=[C:4]([CH:10]([N:12]2[C:16]3=[N:17][CH:18]=[N:19][C:20]([NH2:21])=[C:15]3[C:14]([CH3:22])=[N:13]2)[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].[CH:25]1([B-](F)(F)F)[CH2:27][CH2:26]1.[K+].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:9][C:6]1[C:7]([CH3:8])=[C:2]([CH:25]2[CH2:27][CH2:26]2)[C:3]([O:23][CH3:24])=[C:4]([CH:10]([N:12]2[C:16]3=[N:17][CH:18]=[N:19][C:20]([NH2:21])=[C:15]3[C:14]([CH3:22])=[N:13]2)[CH3:11])[CH:5]=1
F[B-](F)(F)C1CC1
COc1c(C(C)n2nc(C)c3c(N)ncnc32)cc(Cl)c(C)c1Br
null
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
O=P([O-])([O-])[O-]
[K+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
Cc1ccccc1
O
null
null
null
null
null
null
null
null
null
110
null
To a microwave vial was added 1-[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (15 mg, 0.037 mmol, from peak 1 from Example 167, step 4), potassium cyclopropyltrifluoroborate (8 mg, 0.06 mmol, from Frontier Scientific, item # C10298), potassium phosphate (23 mg, 0.11 mmol), and tetrakis(triphenylphosphine)palladium (4.2 mg, 0.0036 mmol) and then toluene (0.3 mL)/water (0.1 mL). The vial was sealed and degassed with N2 three times. The reaction was heat at 110° C. for 20 h. The crude was purified using RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (1.1 mg, 8%). The product was isolated as a single enantiomer. LCMS calculated for C19H23ClN5O (M+H)+: m/z=372.2; Found: 372.2.
COc1c(C(C)n2nc(C)c3c(N)ncnc32)cc(Cl)c(C)c1C1CC1
null
8
null
5,787
ord_dataset-a5669edbeffe43bf8514c1bfede8f882
null
1976-01-01T00:04:00
true
[Cl:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]2[NH:6][C:7](=[O:15])[C:8]3[CH2:14][S:13][CH2:12][C:9]=3[N:10]([CH3:11])[C:4]=2[CH:3]=1.N1C=CC=CC=1.ClN1C(=O)CCC1=O>O>[Cl:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]2[NH:6][C:7](=[O:15])[C:8]3[C:9](=[CH:12][S:13][CH:14]=3)[N:10]([CH3:11])[C:4]=2[CH:3]=1
CN1C2=C(CSC2)C(=O)Nc2cc(Cl)c(Cl)cc21
null
null
O=C1CCC(=O)N1Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
c1ccncc1
O
null
null
null
null
null
null
null
null
null
null
null
To a suspension of 0.40 g. of 6,7-dichloro-1,3,4,9-tetrahydro-4-methyl-10H-thieno[3,4-b] [1,5]benzodiazepin-10-one in 2.7 ml. of dry pyridine is added, in portions, a total of 0.18 g. of N-chlorosuccinimide. The resulting solution is heated on a steam bath for 15 minutes, cooled and diluted with water. The solid which separates is collected and recrystallized from methanol-water to give off-white crystals, m.p. 270°-272°C. (dec.).
CN1c2cc(Cl)c(Cl)cc2NC(=O)c2cscc21
null
null
null
1,084,956
ord_dataset-afd812677c134591a99f46ce28de2524
null
2011-01-01T00:08:00
true
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([CH:20]=[O:21])=[C:12]2Cl)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([CH:20]=[O:21])=[C:12]2[N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
CC(C)(C)c1ccc(-n2c(Cl)c(C=O)c3ccccc32)cc1
C1CCNCC1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1-(4-tert-Butylphenyl)-2-chloro-1H-indole-3-carboxaldehyde is reacted with piperidine as described in Step 2 of Example 29 to afford 1-(4-tert-butylphenyl)-2-piperidin-1-yl-1H-indole-3-carboxaldehyde (87% yield) as an off-white solid. TLC (silica gel, heptane-30% ethyl acetate); Rf=0.23; ESI/MS 361 (M+H); RT=4.48 min; NMR 10.14 (1H, s); 8.11 (1H, d, J=6 Hz); 7.66 (2H, d); 7.46 (2H, d); 7.16 (2H, m); 6.91 (1H, d, J=9 Hz); 3.27 (4H, m); 1.46 (6H, m); 1.36 (9H, s).
CC(C)(C)c1ccc(-n2c(N3CCCCC3)c(C=O)c3ccccc32)cc1
null
87
null
1,166,526
ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880
null
2012-01-01T00:05:00
true
CN(C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([S:20]([C:23]([F:26])([F:25])[F:24])(=[O:22])=[O:21])[CH:15]=2)[N:8]=1)=O.[Cl:28][C:29]1[CH:30]=[C:31]([NH:35][NH2:36])[CH:32]=[CH:33][CH:34]=1>>[Cl:28][C:29]1[CH:30]=[C:31]([N:35]2[C:5]([C:7]3[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([S:20]([C:23]([F:26])([F:24])[F:25])(=[O:22])=[O:21])[CH:15]=4)[N:8]=3)=[CH:4][CH:3]=[N:36]2)[CH:32]=[CH:33][CH:34]=1
CN(C)/C=C/C(=O)c1nn(-c2cccc(S(=O)(=O)C(F)(F)F)c2)ccc1=O
NNc1cccc(Cl)c1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
The product was obtained starting from 3-((E)-3-Dimethylamino-acryloyl)-1-(3-trifluoromethansulfonyl-phenyl)-1H-pyridazin-4-one (A-33) and 3-chloro-phenylhydrazine according to the method described for example 1. MS: M=481.0 (M+H)+
O=c1ccn(-c2cccc(S(=O)(=O)C(F)(F)F)c2)nc1-c1ccnn1-c1cccc(Cl)c1
null
null
null
1,509,409
ord_dataset-1a1aa5d1c3224edca0aec6e3398da985
null
2014-01-01T00:11:00
true
[Cl:1][C:2]1[C:3]([O:30][C@H:31]2[CH2:36][CH2:35][CH2:34][CH2:33][C@@H:32]2[C:37]2[N:41]([CH2:42][O:43][CH2:44][CH2:45][O:46][CH3:47])[N:40]=[CH:39][CH:38]=2)=[CH:4][C:5]([F:29])=[C:6]([S:8]([N:11](CC2C=CC(OC)=CC=2OC)[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]=2)(=[O:10])=[O:9])[CH:7]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[C:3]([O:30][C@H:31]2[CH2:36][CH2:35][CH2:34][CH2:33][C@@H:32]2[C:37]2[N:41]([CH2:42][O:43][CH2:44][CH2:45][O:46][CH3:47])[N:40]=[CH:39][CH:38]=2)=[CH:4][C:5]([F:29])=[C:6]([S:8]([NH:11][C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]=2)(=[O:10])=[O:9])[CH:7]=1
COCCOCn1nccc1[C@H]1CCCC[C@@H]1Oc1cc(F)c(S(=O)(=O)N(Cc2ccc(OC)cc2OC)c2ccncn2)cc1Cl
null
null
CC[SiH](CC)CC
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
ClCCl
O=C(O)C(F)(F)F
null
null
null
null
null
null
null
null
null
null
null
The reaction and aftertreatment were conducted in the same manner as in Example 1b by using the 5-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-{[(1S,2R)-2-{1-[(2-methoxyethoxy)methyl]-1H-pyrazol-5-yl}cyclohexyl]oxy}-N-(pyrimidin-4-yl)benzenesulfonamide (154 mg, 0.223 mmol) prepared in Example 158c, triethylsilane (0.20 mL), trifluoroacetic acid (1.0 mL) and dichloromethane (2.0 mL), to yield the title compound (120 mg, 99%) as a colorless oil.
COCCOCn1nccc1[C@H]1CCCC[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2ccncn2)cc1Cl
null
99.6
null
685,579
ord_dataset-359b8fc87f4244be89d6f02bc5036eac
null
2005-01-01T00:09:00
true
[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][C:9]=1[NH2:18])([CH3:4])([CH3:3])[CH3:2].C([O:24][C:25](=O)[CH2:26][C:27]([C:29]1[CH:34]=[CH:33][N:32]=[C:31]([C:35]2[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=2)[CH:30]=1)=[O:28])(C)(C)C>>[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][C:9]=1[NH:18][C:25](=[O:24])[CH2:26][C:27]([C:29]1[CH:34]=[CH:33][N:32]=[C:31]([C:35]2[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=2)[CH:30]=1)=[O:28])([CH3:4])([CH3:2])[CH3:3]
CC(C)(C)OC(=O)CC(=O)c1ccnc(-c2cccnc2)c1
CC(C)(C)OC(=O)Nc1ccc(C(F)(F)F)cc1N
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
The title compound was prepared from (2-amino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J3) (214 mg, 0.75 mmol) and 3-[2,3′]bipyridinyl-4-yl-3-oxo-propionic acid tert-butyl ester (Example K57) (224 mg, 0.75 mmol) according to the general procedure M. Obtained as a yellow foam (268 mg, 71%).
CC(C)(C)OC(=O)Nc1ccc(C(F)(F)F)cc1NC(=O)CC(=O)c1ccnc(-c2cccnc2)c1
null
null
null
1,100,664
ord_dataset-af85e6f81c2d49f08086afd6d9e6959c
null
2011-01-01T00:10:00
true
[CH3:1][NH:2][CH3:3].[Cl:4][C:5]1[N:6]=[C:7](Cl)[C:8]2[S:13][C:12]([CH3:14])=[CH:11][C:9]=2[N:10]=1.C(N(CC)CC)C>C(O)C>[Cl:4][C:5]1[N:6]=[C:7]([N:2]([CH3:3])[CH3:1])[C:8]2[S:13][C:12]([CH3:14])=[CH:11][C:9]=2[N:10]=1
CNC
Cc1cc2nc(Cl)nc(Cl)c2s1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCN(CC)CC
CCO
null
null
null
null
null
null
null
null
null
null
2
To a solution of 50% aqueous dimethyl amine (0.15 g) in ethanol (5 mL) were added 2,4-dichloro-6-methylthieno[3,2-d]pyrimidine (0.25 g) and triethylamine (0.12 g) at room temperature, and the mixture was stirred for 2 h. The reaction mixture was concentrated under reduced pressure and diluted with chloroform and water, and then the aqueous layer was extracted with chloroform. The organic layer was washed with 1 M hydrochloric acid and saturated brine and then dried with anhydrous magnesium sulfate, the desiccant was removed by filtration, and the filtrate was concentrated under reduced pressure and crystallized with diethyl ether to obtain 2-chloro-N,N,6-trimethylthieno[3,2-d]pyrimidin-4-amine (0.16 g). (2) To a mixture of 2-chloro-N,N,6-trimethylthieno[3,2-d]pyrimidin-4-amine (0.150 g), Pd2(dba)3 (0.033 g), (±)-BINAP (0.067 g), 1-((3R,4R)-3-amino-4-hydroxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.26 g), and 1,4-dioxane (8 mL) was added sodium t-butoxide (0.21 g) under nitrogen atmosphere, and the mixture was stirred at 60° C. for 5 h. The reaction mixture was diluted with ethyl acetate and water, then the interlayer was removed by Celite filtration, and the organic layer was washed with saturated brine. The organic layer was dried with anhydrous magnesium sulfate, then the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (silica gel, chloroform/methanol, and NH silica gel, ethyl acetate) to obtain light yellow amorphous 1-((3R,4R)-3-(4-dimethylamino-6-methylthieno[3,2-d]pyrimidin-2-ylamino)-4-hydroxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.097 g).
Cc1cc2nc(Cl)nc(N(C)C)c2s1
null
61.6
null
1,276,795
ord_dataset-d5c54236ecd94d61aaa071461bcfc426
null
2013-01-01T00:04:00
true
[N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH2:11][N:12]3[C:16]4=[N:17][C:18]([C:21](=O)[CH3:22])=[CH:19][N:20]=[C:15]4[N:14]=[N:13]3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.Cl.[NH:26]1[CH2:30][CH2:29][C@@H:28]([O:31][NH2:32])[CH2:27]1>>[NH:26]1[CH2:30][CH2:29][C@@H:28]([O:31]/[N:32]=[C:21](/[C:18]2[N:17]=[C:16]3[N:12]([CH2:11][C:7]4[CH:6]=[C:5]5[C:10](=[CH:9][CH:8]=4)[N:1]=[CH:2][CH:3]=[CH:4]5)[N:13]=[N:14][C:15]3=[N:20][CH:19]=2)\[CH3:22])[CH2:27]1
NO[C@@H]1CCNC1
CC(=O)c1cnc2nnn(Cc3ccc4ncccc4c3)c2n1
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
The title compound was prepared from 1-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)ethanone (22.4) (25 mg, 0.082 mmol) and (R)—O-(pyrrolidin-3-yl)hydroxylamine dihydrochloride in 60% yield using the same procedure as described in the synthesis of example 22. 1H-NMR (400 MHz, CDCl3) δ ppm 9.41 (s, 1H), 8.92 (d, 1H), 8.13 (d, 1H), 8.09 (d, 1H), 7.91 (s, 1H), 7.82 (d, 1H), 7.41 (dd, 1H), 6.10 (s, 2H), 5.30 (s, 1H), 5.09 (s, 1H), 3.31 (m, 3H), 2.38 (s, 3H), 2.25 (m, 2H). LCMS (method B): [MH]+=389, tR=1.17 min.
C/C(=N\O[C@@H]1CCNC1)c1cnc2nnn(Cc3ccc4ncccc4c3)c2n1
null
60
null
769,650
ord_dataset-8214eb8444a44dc2900ccb42dbeff15e
null
2007-01-01T00:05:00
true
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C@@H:10]2[NH:15][CH2:14][CH2:13][N:12]([C:16]3[C:25]4[CH:24]=[C:23]([CH3:26])[S:22][C:21]=4[NH:20][C:19]4[CH:27]=[CH:28][CH:29]=[CH:30][C:18]=4[N:17]=3)[CH2:11]2)=[CH:4][CH:3]=1.C=O.[C:33](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C@@H:10]2[N:15]([CH3:33])[CH2:14][CH2:13][N:12]([C:16]3[C:25]4[CH:24]=[C:23]([CH3:26])[S:22][C:21]=4[NH:20][C:19]4[CH:27]=[CH:28][CH:29]=[CH:30][C:18]=4[N:17]=3)[CH2:11]2)=[CH:4][CH:3]=1
Cc1cc2c(s1)Nc1ccccc1N=C2N1CCN[C@@H](CCc2ccc(Cl)cc2)C1
CC(=O)O[BH-](OC(C)=O)OC(C)=O
null
C=O
[Na+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
ClCCCl
null
null
null
null
null
null
null
null
null
null
25
0.08
Combine 10-((S)-3-[2-(4-chloro-phenyl)-ethyl]-piperazin-1-yl)-2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulene (430.9 mg, 0.99 mmol), formaldehyde (88.0 μL, 1.08 mmol, 37% in water), and 1,2-dichloroethane (30.0 ml). Stir the mixture at ambient temperature for 5 minutes and then add sodium triacetoxyborohydride (313.5 mg, 1.48 mmol). After stirring for 30 minutes at ambient temperature, quench the reaction with saturated sodium bicarbonate. Remove the organic portion, extract the aqueous with dichloromethane and combine, wash (brine), dry (sodium sulfate), and reduce the extracts to residue. Purify the residue on silica gel using dichloromethane/methanol (95:5) to give 365.2 mg (82%) of the title compound as a brown foam: mp 79°, dec; mass spectrum (ion spray): m/z=451.2 (M+1).
Cc1cc2c(s1)Nc1ccccc1N=C2N1CCN(C)[C@@H](CCc2ccc(Cl)cc2)C1
null
81.8
null
1,068,325
ord_dataset-5df93261afc143c3ae919a57ff4fc1d4
null
2011-01-01T00:07:00
true
C([O:8][C:9]1[CH:38]=[CH:37][C:12]([CH2:13][NH:14][C:15](=[O:36])[CH2:16][N:17]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[C:29]=2[CH3:35])[S:18]([C:21]2[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=2)(=[O:20])=[O:19])=[CH:11][CH:10]=1)C1C=CC=CC=1>CO.C1COCC1.[Pd]>[Cl:34][C:30]1[C:29]([CH3:35])=[C:28]([N:17]([S:18]([C:21]2[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=2)(=[O:19])=[O:20])[CH2:16][C:15]([NH:14][CH2:13][C:12]2[CH:37]=[CH:38][C:9]([OH:8])=[CH:10][CH:11]=2)=[O:36])[CH:33]=[CH:32][CH:31]=1
Cc1ccc(S(=O)(=O)N(CC(=O)NCc2ccc(OCc3ccccc3)cc2)c2cccc(Cl)c2C)cc1
null
null
[Pd]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1CCOC1
CO
null
null
null
null
null
null
null
null
null
25
6.5
668 mg of N-[4-(benzyloxy)benzyl]-N2-(3-chloro-2-methylphenyl)-N2-[(4-methylphenyl)sulfonyl]glycinamide was dissolved in 5.00 mL of methanol and 2.00 mL of THF, and 70 mg of 10% Pd—C (Kawaken, AD type, water content 54%) was added thereto, followed by stirring at room temperature for 6.5 hours under a hydrogen atmosphere. The reaction liquid was filtered through Celite, the filtrate was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50 to 30:70) to obtain a product, which was recrystallized from ethanol/water to obtain 373 mg of N2-(3-chloro-2-methylphenyl)-N-(4-hydroxybenzyl)-N2-[(4-methylphenyl)sulfonyl] glycinamide.
Cc1ccc(S(=O)(=O)N(CC(=O)NCc2ccc(O)cc2)c2cccc(Cl)c2C)cc1
null
66.8
null
589,725
ord_dataset-7a74d48eeefd45aba53e7258f3ae067a
null
2003-01-01T00:04:00
true
[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1[C:13]([NH2:14])=[CH:12][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])=[C:10]([O:22][CH2:23][C:24]([F:27])([F:26])[F:25])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].C([O:33][C:34](=O)[CH2:35][C:36]([C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([C:44]2[O:48][N:47]=[C:46]([CH3:49])[CH:45]=2)[CH:39]=1)=[O:37])(C)(C)C>>[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1[C:13]([NH:14][C:34](=[O:33])[CH2:35][C:36]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([C:44]3[O:48][N:47]=[C:46]([CH3:49])[CH:45]=3)[CH:39]=2)=[O:37])=[CH:12][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])=[C:10]([O:22][CH2:23][C:24]([F:25])([F:26])[F:27])[CH:9]=1)([CH3:4])([CH3:2])[CH3:3]
CC(C)(C)OC(=O)Nc1cc(OCC(F)(F)F)c(-c2ccccc2F)cc1N
Cc1cc(-c2cccc(C(=O)CC(=O)OC(C)(C)C)c2)on1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
The title compound was prepared from [5-amino-2′-fluoro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (160 mg, 0.53 mmol) according to the general procedure M. Obtained as a white solid (40 mg).
Cc1cc(-c2cccc(C(=O)CC(=O)Nc3cc(-c4ccccc4F)c(OCC(F)(F)F)cc3NC(=O)OC(C)(C)C)c2)on1
null
null
null
781,458
ord_dataset-8034115bd2ec4d3e95bd3ff7cfde0bde
null
2007-01-01T00:07:00
true
C(O[C:4](=[O:27])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[CH:10][CH:9]=1)=[O:6])C.[O:28]([C:35]1[CH:41]=[CH:40][C:38]([NH2:39])=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.CC(C)([O-])C.[Li+]>C1(C)C(C)=CC=CC=1>[CH2:15]([O:14][C:11]1[CH:10]=[CH:9][C:8]([NH:7][C:5](=[O:6])[C:4]([NH:39][C:38]2[CH:37]=[CH:36][C:35]([O:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:41][CH:40]=2)=[O:27])=[CH:13][CH:12]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]
CCCCCCCCCCCCOc1ccc(NC(=O)C(=O)OCC)cc1
Nc1ccc(Oc2ccccc2)cc1
null
CC(C)(C)[O-]
[Li+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
Cc1ccccc1C
null
null
null
null
null
null
null
null
null
null
null
3
A solution of N-(4-dodecyloxyphenyl)oxalamic acid ethyl ester (10 g, 0.026 mol), 4-phenoxyaniline (5 g, 0.026 mol) and lithium t-butoxide (0.2 g, 0.0026 mol) in xylene (50 mL) isheated to gentle reflux. A distillate of ethanol/xylene is slowly collected; the reaction volume is kept at 50 mL by adding xylene. Heating and distillation continued for 3 hours. The reaction mixture is cooled, the solids are collected and washed sequentially with warm ethyl acetate, ethanol, water and finally ethanol. There is obtained 11.5 g white solid mp: 179–181.
CCCCCCCCCCCCOc1ccc(NC(=O)C(=O)Nc2ccc(Oc3ccccc3)cc2)cc1
null
85.6
null
1,564,779
ord_dataset-4e54080057a44c3887653391e24c90b6
null
2015-01-01T00:03:00
true
[Cl:1][C:2]1[CH:3]=[C:4]([CH:40]=[CH:41][C:42]=1[Cl:43])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C@H:13]2[CH2:39][O:38][C:16]3=[CH:17][C:18]4[CH2:19][C@@H:20]([C:35](O)=[O:36])[N:21]([C@H:25]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[CH2:26][CH2:27][CH3:28])[CH2:22][C:23]=4[CH:24]=[C:15]3[O:14]2)=[CH:9][CH:8]=1.Cl.C[O:46][C:47](=[O:65])[C@@H:48]([NH2:64])[CH2:49][C:50]1[CH:55]=[CH:54][C:53]([C:56]2[CH:61]=[CH:60][C:59]([C:62]#[N:63])=[CH:58][CH:57]=2)=[CH:52][CH:51]=1>>[C:62]([C:59]1[CH:58]=[CH:57][C:56]([C:53]2[CH:54]=[CH:55][C:50]([CH2:49][C@H:48]([NH:64][C:35]([C@@H:20]3[CH2:19][C:18]4[CH:17]=[C:16]5[O:38][CH2:39][C@H:13]([C:10]6[CH:9]=[CH:8][C:7]([O:6][CH2:5][C:4]7[CH:40]=[CH:41][C:42]([Cl:43])=[C:2]([Cl:1])[CH:3]=7)=[CH:12][CH:11]=6)[O:14][C:15]5=[CH:24][C:23]=4[CH2:22][N:21]3[C@H:25]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:26][CH2:27][CH3:28])=[O:36])[C:47]([OH:46])=[O:65])=[CH:51][CH:52]=2)=[CH:61][CH:60]=1)#[N:63]
COC(=O)[C@@H](N)Cc1ccc(-c2ccc(C#N)cc2)cc1
CCC[C@@H](c1ccccc1)N1Cc2cc3c(cc2C[C@H]1C(=O)O)OC[C@H](c1ccc(OCc2ccc(Cl)c(Cl)c2)cc1)O3
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
The title compound was prepared from (3S,8S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-7-((S)-1-phenyl-butyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid and (S)-2-amino-3-(4′-cyano-biphenyl-4-yl)-propionic acid methyl ester hydrochloride according to General Procedures L and B. LCMS (m/z): 868.
CCC[C@@H](c1ccccc1)N1Cc2cc3c(cc2C[C@H]1C(=O)N[C@@H](Cc1ccc(-c2ccc(C#N)cc2)cc1)C(=O)O)OC[C@H](c1ccc(OCc2ccc(Cl)c(Cl)c2)cc1)O3
null
null
null
837,696
ord_dataset-074f86301ec5441ab3b52d902ac06949
null
2008-01-01T00:09:00
true
C(OC([NH:8][CH2:9][CH2:10][O:11][C:12]1[C:17]2[C:18]([CH3:47])=[C:19]([C:21]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([C:30]4[CH:35]=[CH:34][C:33]([S:36]([NH:39][C@@H:40]([CH:44]([CH3:46])[CH3:45])[C:41]([OH:43])=[O:42])(=[O:38])=[O:37])=[CH:32][CH:31]=4)=[CH:26][CH:25]=3)=[O:22])[O:20][C:16]=2[CH:15]=[CH:14][CH:13]=1)=O)(C)(C)C.[C:48]([OH:54])([C:50]([F:53])([F:52])[F:51])=[O:49].C(Cl)Cl>>[NH2:8][CH2:9][CH2:10][O:11][C:12]1[C:17]2[C:18]([CH3:47])=[C:19]([C:21]([NH:23][C:24]3[CH:25]=[CH:26][C:27]([C:30]4[CH:35]=[CH:34][C:33]([S:36]([NH:39][C@@H:40]([CH:44]([CH3:45])[CH3:46])[C:41]([OH:43])=[O:42])(=[O:38])=[O:37])=[CH:32][CH:31]=4)=[CH:28][CH:29]=3)=[O:22])[O:20][C:16]=2[CH:15]=[CH:14][CH:13]=1.[C:48]([OH:54])([C:50]([F:53])([F:52])[F:51])=[O:49]
Cc1c(C(=O)Nc2ccc(-c3ccc(S(=O)(=O)N[C@H](C(=O)O)C(C)C)cc3)cc2)oc2cccc(OCCNC(=O)OC(C)(C)C)c12
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
O=C(O)C(F)(F)F
ClCCl
null
null
null
null
null
null
null
null
null
null
null
The product of Example 177, (S)-2-(4′-{[4-(2-tert-butoxycarbonylamino-ethoxy)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid, was treated with 40% TFA/methylene chloride solution at ambient temperature for four hours to afford (S)-2-(4′-{[4-(2-amino-ethoxy)-3-methyl-benzofuran-2-carbonyl]-amino}-biphenyl-4-sulfonylamino)-3-methyl-butyric acid as a brown solid (TFA salt). MS: calc'd for {M−H]−: 564.65. Found: 564.51.
Cc1c(C(=O)Nc2ccc(-c3ccc(S(=O)(=O)N[C@H](C(=O)O)C(C)C)cc3)cc2)oc2cccc(OCCN)c12
null
null
null
271,122
ord_dataset-a20aed058d7b40bc81fdf50bc5b03f97
null
1993-01-01T00:06:00
true
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([OH:13])[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[CH:14]([N:17]([CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)[C:18](=[O:29])[C:19]1[CH:24]=[CH:23][C:22](Br)=[C:21]([O:26][CH2:27][CH3:28])[CH:20]=1)([CH3:16])[CH3:15].Cl>N1C(C)=CC(C)=CC=1C>[CH:30]1([N:17]([CH:14]([CH3:15])[CH3:16])[C:18](=[O:29])[C:19]2[CH:24]=[CH:23][C:22]([O:13][C:5]3[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)=[C:21]([O:26][CH2:27][CH3:28])[CH:20]=2)[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1
COc1cc(O)cc(OC)c1OC
CCOc1cc(C(=O)N(C(C)C)C2CCCCC2)ccc1Br
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
Cc1cc(C)nc(C)c1
null
null
null
null
null
null
null
null
null
null
null
18
A slurry of cuprous oxide (300 mg, 2.1 mmol) in a solution of 3,4,5-trimethoxyphenol (736 mg, 4.0 mmol) and 4-bromo-3-ethoxybenzoic acid N-isopropyl-N-cyclohexyl amide (1.47 g, 4.0 mmol) in 2,4,6-collidine (20 ml) is refluxed with stirring under a nitrogen atmosphere for 18 hr. The reaction is cooled, poured onto dilute aqueous HCl and extracted three times with ethyl acetate. The combined organic layers are washed twice with saturated aqueous NaCl solution, twice with 5% NaOH solution, twice with saturated NaCl solution and dried (Na2SO4). The drying agent is filtered and the filtrate concentrated in vacuo to give the crude product. This material is chromatographed on silica gel using mixtures of ethyl acetate and hexane as the eluents to give the title compound.
CCOc1cc(C(=O)N(C(C)C)C2CCCCC2)ccc1Oc1cc(OC)c(OC)c(OC)c1
null
null
null
1,636,239
ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d
null
2015-01-01T00:09:00
true
Br[C:2]1[C:3]([O:9][CH3:10])=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH3:11][N:12](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([C:11]#[N:12])=[C:3]([O:9][CH3:10])[CH:4]=1
CN(C)C=O
COc1cc(Cl)ncc1Br
null
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
[C-]#N
[Zn+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
95
12
A solution of 5-bromo-2-chloro-4-methoxypyridine (5.0 g, 22.48 mmol) in DMF (80 mL) was purged with nitrogen for 15 minutes. At this point, Zn(CN)2 (3.96 g, 33.7 mmol) and Pd(Ph3P)4 (2.60 g, 2.25 mmol) were added, successively. The resulting suspension was stirred at 95° C. for 12 hours under nitrogen atmosphere. The reaction mixture was cooled to ambient temperature, and filtered to remove inorganic solid. The solvent (DMF) was evaporated to provide the crude residue as an oil, which was purified on silica gel and eluted with 0-30% ethyl acetate/hexanes to afford the product.
COc1cc(Cl)ncc1C#N
null
null
null
1,283,994
ord_dataset-d5c54236ecd94d61aaa071461bcfc426
null
2013-01-01T00:04:00
true
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:14](Cl)(=[O:24])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23].Cl>C(Cl)Cl>[C:2]1([NH:1][C:14](=[O:24])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
CCCCCCCCCC(=O)Cl
Nc1ccccc1
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
c1ccncc1
ClCCl
null
null
null
null
null
null
null
null
null
25
3
Aniline (2.03 g, 25.0 mmol) was dissolved in CH2Cl2 (30 mL). To the solution were added pyridine (2.22 mL, 27.5 mmol) and decanoyl chloride (5.25 g, 27.5 mmol) in an ice bath. After stirring for 3 h at room temperature, the reaction mixture was poured into 1M HCl (30 mL) and the mixture extracted with CH2Cl2 (3×100 mL). The organic extracts were washed with water (50 mL), brine (50 mL), dried over Na2SO4, filtered, and concentrated to give 5.62 g (22.8 mmol, 91%) of N-phenyldecanamide as a white solid, mp 65-66° C. (lit5 mp 65-66° C.); 1H NMR (300 MHz, CDCl3) δ 0.87 (t, 3H, J=6.9 Hz), 1.26 (m, 12H), 1.72 (m, 2H), 2.35 (t, 2H, J=7.8 Hz), 7.10 (t, 2H, J=7.8 Hz), 7.31 (t, 1H, J=7.8 Hz) 7.50 (t, 2H, J=7.9 Hz); 13C NMR (75 MHz, CDCl3) δ 13.9, 22.5, 25.7, 29.2, 29.2, 29.3, 29.3, 31.7, 37.5, 120.1, 124.0, 128.7, 138.1, 172.3.
CCCCCCCCCC(=O)Nc1ccccc1
null
91.2
null
2,336
ord_dataset-a0bc986c3cf848c2a1ea93b297d1ad89
null
1976-01-01T00:02:00
true
Cl[CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:25]=[CH:24][C:10]2[S:11][C:12]3[CH:17]=[CH:16][C:15]([C:18](=[O:23])[CH2:19][CH2:20][CH2:21]Cl)=[CH:14][C:13]=3[C:9]=2[CH:8]=1)=[O:6].[NH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1.[I-].[K+]>O1CCCC1>[N:26]1([CH2:2][CH2:3][CH2:4][C:5]([C:7]2[CH:25]=[CH:24][C:10]3[S:11][C:12]4[CH:17]=[CH:16][C:15]([C:18](=[O:23])[CH2:19][CH2:20][CH2:21][N:26]5[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]5)=[CH:14][C:13]=4[C:9]=3[CH:8]=2)=[O:6])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1
O=C(CCCCl)c1ccc2sc3ccc(C(=O)CCCCl)cc3c2c1
C1CCNCC1
null
[I-]
[K+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1CCOC1
null
null
null
null
null
null
null
null
null
null
125
24
A mixture of 28.0 g (0.072 mole) of 2,8-bis(4-chlorobutyryl)dibenzothiophene, 49.4 g (0.58 mole) of piperidine and 2.0 g of potassium iodide in 200 ml of tetrahydrofuran is heated at 125°C with stirring for 24 hours in a Parr general purpose bomb. The reaction mixture is cooled, filtered, and the filtrate is evaporated in vacuo leaving a residue which is washed with water and recrystallized twice from acetone to give 2,8-bis(4-piperidinobutyryl)dibenzothiophene, M.P. 93°-95°C.
O=C(CCCN1CCCCC1)c1ccc2sc3ccc(C(=O)CCCN4CCCCC4)cc3c2c1
null
null
null
738,839
ord_dataset-437aa6654d5044ddaef3346dc4c6e08a
null
2006-01-01T00:11:00
true
FC(F)(F)C(O)=O.ClC1C=CC([CH:15]2N[C:18]([C:20]3C=CC(OC)=[CH:22][C:21]=3OCC)=[N:17][CH:16]2[CH:31]2CCCC2)=CC=1.[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([CH:43]2[N:47]([C:48]([N:50]3[CH2:55]CN(C)C[CH2:51]3)=[O:49])[C:46]([C:57]3[CH:62]=[CH:61][C:60]([O:63][CH3:64])=[CH:59][C:58]=3[O:65][CH2:66][CH3:67])=[N:45][CH:44]2[CH2:68][CH:69]2[CH2:73][CH2:72][CH2:71]C2)=[CH:39][CH:38]=1>>[Cl:36][C:37]1[CH:38]=[CH:39][C:40]([CH:43]2[N:47]([C:48]([N:50]3[CH2:55][CH2:31][CH:16]([N:17]4[CH2:22][CH2:21][CH2:20][CH2:18]4)[CH2:15][CH2:51]3)=[O:49])[C:46]([C:57]3[CH:62]=[CH:61][C:60]([O:63][CH3:64])=[CH:59][C:58]=3[O:65][CH2:66][CH3:67])=[N:45][CH:44]2[CH:68]2[CH2:69][CH2:73][CH2:72][CH2:71]2)=[CH:41][CH:42]=1
CCOc1cc(OC)ccc1C1=NC(CC2CCCC2)C(c2ccc(Cl)cc2)N1C(=O)N1CCN(C)CC1
CCOc1cc(OC)ccc1C1=NC(C2CCCC2)C(c2ccc(Cl)cc2)N1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
O=C(O)C(F)(F)F
null
null
null
null
null
null
null
null
null
null
null
null
[5-(4-Chloro-phenyl)-4-cyclopentyl-2-(2-ethoxy-4-methoxy-phenyl)-4,5-dihydro-imidazol-1-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone was prepared from 5-(4-chloro-phenyl)-4-cyclopentyl-2-(2-ethoxy-4-methoxy-phenyl)-4,5-dihydro-1H-imidazole, trifluoroacetate salt (Example 19) in an analogous manner as described for the preparation of [5-(4-chloro-phenyl)-4-cyclopentylmethyl-2-(2-ethoxy-4-methoxy-phenyl)-4,5-dihydro-imidazol-1-yl]-(4-methyl-piperazin-1-yl)-methanone (Example 24). HR-MS (ES, m/z) observed 579.3104, calculated for C33H44N4O3Cl [(M+H)+]579.3097.
CCOc1cc(OC)ccc1C1=NC(C2CCCC2)C(c2ccc(Cl)cc2)N1C(=O)N1CCC(N2CCCC2)CC1
null
null
null
272,082
ord_dataset-347c0709d28a44dea43ca42052be4db3
null
1993-01-01T00:07:00
true
[CH2:1]([S:3][C:4]1[C:5]2[C:6]3[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[C:7]=3[CH:14]=[CH:15][CH:16]=2)C.[H-].[Na+].[CH2:19](I)[CH2:20][CH2:21][CH3:22]>>[CH2:19]([N:9]1[C:10]2[C:6]3[C:5](=[CH:16][CH:15]=[CH:14][C:7]=3[C:8]1=[O:13])[C:4]([S:3][CH3:1])=[CH:12][CH:11]=2)[CH2:20][CH2:21][CH3:22]
CCCCI
CCSc1ccc2c3c(cccc13)C(=O)N2
null
[H-]
[Na+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
A mixture of 2.15 g of 6-(methylthio)-benz[cd]indol-2(1H)-one (Example 12), 0.6 g of 60% sodium hydride and 1.7 ml of butyl iodide in 70 ml are reacted as described in Example 16 giving 1.85 g of the desired product as a solid, m.p. 75°-77° C.
CCCCN1C(=O)c2cccc3c(SC)ccc1c23
null
null
null
17,728
ord_dataset-d625331704b34593871e69cd09a5cd83
null
1976-01-01T00:12:00
true
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]1[NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:6]1[C:5]2=[O:19].[C:20]([C:24]1[CH:32]=[CH:31][CH:30]=[CH:29][C:25]=1[C:26](Cl)=[O:27])([O:22][CH3:23])=[O:21]>>[C:20]([C:24]1[CH:32]=[CH:31][CH:30]=[CH:29][C:25]=1[C:26]([N:12]1[C:7]2=[N:8][C:9]3[C:4]([C:5](=[O:19])[N:6]2[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]1=2)=[CH:3][C:2]([Br:1])=[CH:11][CH:10]=3)=[O:27])([O:22][CH3:23])=[O:21]
COC(=O)c1ccccc1C(=O)Cl
O=c1c2cc(Br)ccc2nc2[nH]c3ccccc3n12
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
6-(2-Carbomethoxybenzoyl)-2-bromobenzimidazo[2,1-b]quinazolin-12(6H)one is prepared with 2-bromobenzimidazo[2,1-b]quinazolin-12(6H)one and 2-carbomethoxybenzoylchloride.
COC(=O)c1ccccc1C(=O)n1c2ccccc2n2c(=O)c3cc(Br)ccc3nc12
null
null
null
727,070
ord_dataset-eb4226b4f7644a01a737e7547b70014a
null
2006-01-01T00:09:00
true
[CH2:1]([C:5]1[CH:10]=[CH:9][C:8](/[C:11](/[CH3:16])=[CH:12]/[C:13]([OH:15])=O)=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].[NH:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[CH2:22][N:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8](/[C:11](/[CH3:16])=[CH:12]/[C:13]([N:17]2[CH2:21][CH2:20][CH2:19][C@H:18]2[CH2:22][N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[O:15])=[CH:9][CH:10]=1)[CH:2]([CH3:3])[CH3:4]
C/C(=C\C(=O)O)c1ccc(CC(C)C)cc1
C1CCN(C[C@@H]2CCCN2)CC1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
130 mg of the title compound were synthesized as described for (E)-3-(4-bromophenyl)-1-((S)-2-((pyrrolidin-1-yl)methyl)pyrrolidin-1-yl)propenone, using (E)-3-(4-(Isobutyl)phenyl)but-2-enoic acid instead of (E)-4-bromocinnamic acid and 1-(((S)-pyrrolidin-2-yl)methyl)piperidine instead of (S)-2-((pyrrolidin-1-yl)methyl)pyrrolidine.
C/C(=C\C(=O)N1CCC[C@H]1CN1CCCCC1)c1ccc(CC(C)C)cc1
null
null
null
1,171,882
ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880
null
2012-01-01T00:05:00
true
Br[C:2]1[C:7]([F:8])=[CH:6][C:5]([O:9][CH3:10])=[CH:4][C:3]=1[F:11].[Cl:12][C:13]1[CH:18]=[C:17]([CH2:19][C:20]([O:22]C)=[O:21])[CH:16]=[CH:15][C:14]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:12][C:13]1[CH:18]=[C:17]([CH2:19][C:20]([OH:22])=[O:21])[CH:16]=[CH:15][C:14]=1[C:2]1[C:7]([F:8])=[CH:6][C:5]([O:9][CH3:10])=[CH:4][C:3]=1[F:11]
COc1cc(F)c(Br)c(F)c1
COC(=O)Cc1ccc(B(O)O)c(Cl)c1
null
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
O=C([O-])[O-]
[Na+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
COCCOC
null
null
null
null
null
null
null
null
null
null
85
17
A solution of 4-bromo-3,5-difluoroanisole (645 mg, 2.89 mmol) and 2-chloro-4-(2-methoxy-2-oxoethyl)phenylboronic acid (Intermediate 2-6; 859 mg, 3.76 mmol) and sodium carbonate (2.89 mL, 5.78 mmol), tetrakis(triphenylphosphine)palladium(0) (207 mg, 0.18 mmol) in DME (20 mL) was degassed and then stirred at 85° C. for 17 hours. The reaction mixture was allowed to cool, evaporated and partitioned between EtOAc (75 mL), water (40 mL) and saturated brine (15 mL), The aqueous phase was acidified with 2M HCl and extracted into EtOAc (2×125 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford 2-(2-chloro-2′,6′-difluoro-4′-methoxybiphenyl-4-yl)acetic acid (654 mg, 72.4%) as a white solid, which was used without further purification.
COc1cc(F)c(-c2ccc(CC(=O)O)cc2Cl)c(F)c1
null
72.4
null
1,308,012
ord_dataset-78c3f723155a4347a902b53bcee1524d
null
2013-01-01T00:06:00
true
[OH:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C@H:7]2[CH2:12][O:11][C@@H:10]([CH2:13][CH2:14][CH2:15][NH:16][C:17](=[O:19])[CH3:18])[O:9][CH2:8]2)=[CH:4][CH:3]=1.[CH:22]1(Br)[CH2:26][CH2:25][CH2:24][CH2:23]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH:22]1([O:1][C:2]2[CH:3]=[CH:4][C:5]([O:6][C@H:7]3[CH2:8][O:9][C@@H:10]([CH2:13][CH2:14][CH2:15][NH:16][C:17](=[O:19])[CH3:18])[O:11][CH2:12]3)=[CH:20][CH:21]=2)[CH2:26][CH2:25][CH2:24][CH2:23]1
BrC1CCCC1
CC(=O)NCCC[C@H]1OC[C@@H](Oc2ccc(O)cc2)CO1
null
O=C([O-])[O-]
[Cs+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CN(C)C=O
null
null
null
null
null
null
null
null
null
null
null
8
cis-N-{3-[5-(4-Hydroxyphenoxy)-[1,3]dioxan-2-yl]propyl}acetamide (18.6 mg, 0.063 mmol), cyclopentyl bromide (11.3 mg, 0.076 mmol) and cesium carbonate (24.6 mg, 0.076 mmol) were stirred in 3 ml of DMF at room temperature for 3 h. Addition of 11 mg of cyclopentyl bromide and 20 mg of cesium carbonate on each of two occasions was followed by stirring for a total of 8 h and concentrating, and the residue was taken up in ethyl acetate and water. The organic phase was separated off, concentrated and purified by preparative HPLC (PR18, acetonitrile/water 0.1% TFA). Yield: 8.5 mg (37%), M+H+: 364.22.
CC(=O)NCCC[C@H]1OC[C@@H](Oc2ccc(OC3CCCC3)cc2)CO1
null
null
null
1,267,153
ord_dataset-d3580a12b15e46cc91aa73f4f1a4a8cc
null
2013-01-01T00:03:00
true
CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[OH:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][NH:32][C:33]([C:35]1[CH:36]=[C:37]([S:41]([C:44]2[CH:45]=[C:46]3[C:51](=[C:52]([CH3:54])[CH:53]=2)[N:50]=[CH:49][C:48]([C:55]([NH2:57])=[O:56])=[C:47]3[NH:58][C:59]2[CH:64]=[CH:63][CH:62]=[C:61]([O:65][CH3:66])[CH:60]=2)(=[O:43])=[O:42])[CH:38]=[CH:39][CH:40]=1)=[O:34].C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:66][O:65][C:61]1[CH:60]=[C:59]([NH:58][C:47]2[C:46]3[C:51](=[C:52]([CH3:54])[CH:53]=[C:44]([S:41]([C:37]4[CH:38]=[CH:39][CH:40]=[C:35]([C:33](=[O:34])[NH:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH:24]=[O:23])[CH:36]=4)(=[O:43])=[O:42])[CH:45]=3)[N:50]=[CH:49][C:48]=2[C:55]([NH2:57])=[O:56])[CH:64]=[CH:63][CH:62]=1
COc1cccc(Nc2c(C(N)=O)cnc3c(C)cc(S(=O)(=O)c4cccc(C(=O)NCCCCCCCCO)c4)cc23)c1
null
null
CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
O=C([O-])O
[Na+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CN(C)C=O
null
null
null
null
null
null
null
null
null
null
null
3
Dess-Martin reagent (105 mg, 0.249 mmol) was added to a stirring solution of Intermediate 70 (77 mg, 0.124 mmol) in DMF (2 mL) at rt. The resulting solution was stirred for 3 h and poured into satd. NaHCO3 (50 mL). The precipitate was filtered, washed with H2O, and dried to give the title compound (70 mg) as a yellow solid. The compound was used with no further purification. ES/MS calcd. for C33H37N4O6S+ 617.2. Found m/z=617.3 (M+H)+.
COc1cccc(Nc2c(C(N)=O)cnc3c(C)cc(S(=O)(=O)c4cccc(C(=O)NCCCCCCCC=O)c4)cc23)c1
null
91.5
null
740,343
ord_dataset-437aa6654d5044ddaef3346dc4c6e08a
null
2006-01-01T00:11:00
true
[CH3:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[CH:11]1([CH2:14][N:15]2[C:23]3[N:22]=[C:21]([CH2:24][C:25]4[CH:30]=[CH:29][C:28]([NH:31][CH3:32])=[CH:27][CH:26]=4)[NH:20][C:19]=3[C:18](=[O:33])[N:17]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[F:41])[C:16]2=[O:42])[CH2:13][CH2:12]1>>[CH:11]1([CH2:14][N:15]2[C:23]3[N:22]=[C:21]([CH2:24][C:25]4[CH:26]=[CH:27][C:28]([N:31]([CH3:32])[C:7](=[O:9])[C:6]5[CH:10]=[C:2]([CH3:1])[CH:3]=[N:4][CH:5]=5)=[CH:29][CH:30]=4)[NH:20][C:19]=3[C:18](=[O:33])[N:17]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[F:41])[C:16]2=[O:42])[CH2:13][CH2:12]1
CNc1ccc(Cc2nc3c([nH]2)c(=O)n(Cc2ccccc2F)c(=O)n3CC2CC2)cc1
Cc1cncc(C(=O)O)c1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
This compound was prepared by a method similar to that described in example 79 except that 5-methylnicotinic acid (Lancaster) was used in place of N-acetyl-6-amino-2-pyridine carboxylic acid and 2 equivalents of 3-cyclopropylmethyl-8-[4-(methylamino)-benzyl]-1-(2-fluorobenzyl)-3,7-dihydropurine-2,6-dione were used. The product was purified by chromatography using silica gel eluted with 96:4 chloroform/methanol. MS, m/z(M+)=553.2365.
Cc1cncc(C(=O)N(C)c2ccc(Cc3nc4c([nH]3)c(=O)n(Cc3ccccc3F)c(=O)n4CC3CC3)cc2)c1
null
null
null
1,329,362
ord_dataset-cfad8b3f00044bcda60a96b019f09872
null
2013-01-01T00:08:00
true
[C:1]([C:5]1[N:10]=[CH:9][C:8]([C:11]2[N:12]([C:32](Cl)=[O:33])[C@@:13]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)([CH3:24])[C@@:14]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)([CH3:16])[N:15]=2)=[C:7]([O:35][CH2:36][CH3:37])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[O:40]=[S:41]1(=[O:53])[CH2:46][CH2:45][CH:44]([N:47]2[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)[CH2:43][CH2:42]1>>[C:1]([C:5]1[N:10]=[CH:9][C:8]([C:11]2[N:12]([C:32]([N:50]3[CH2:51][CH2:52][N:47]([CH:44]4[CH2:43][CH2:42][S:41](=[O:53])(=[O:40])[CH2:46][CH2:45]4)[CH2:48][CH2:49]3)=[O:33])[C@@:13]([C:25]3[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=3)([CH3:24])[C@@:14]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)([CH3:16])[N:15]=2)=[C:7]([O:35][CH2:36][CH3:37])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)Cl
O=S1(=O)CCC(N2CCNCC2)CC1
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
In a manner analogous to the method described in examples 8, (4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride (example 51) was coupled with 1-(1,1-dioxo-hexahydro-1λ6-thiopyran-4-yl)-piperazine dihydrochloride (prepared as described in Ding, Q. et al. WO2007063013) to give the title compound. HR-MS (ES, m/z) calculated for C38H48N5O4SCl2 [(M+H)+] 740.2799, observed 740.2802.
CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCN(C2CCS(=O)(=O)CC2)CC1
null
null
null
626,781
ord_dataset-e44331dc51de453ca14b7032593c1958
null
2004-01-01T00:02:00
true
[CH3:1][C:2]1[C:6]2[C:7](=[O:11])[CH2:8][CH2:9][CH2:10][C:5]=2[S:4][CH:3]=1.C1C(=O)N([Br:19])C(=O)C1.O>C(Cl)Cl>[Br:19][C:3]1[S:4][C:5]2[CH2:10][CH2:9][CH2:8][C:7](=[O:11])[C:6]=2[C:2]=1[CH3:1]
Cc1csc2c1C(=O)CCC2
O=C1CCC(=O)N1Br
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
O
ClCCl
null
null
null
null
null
null
null
null
null
25
3
To a stirred solution of 3-methyl-4-oxo-4,5,6,7-tetrahydrobenzothiophene (500 mg, 3.01 mmol) in CH2Cl2 (15 mL) was added NBS (536 mg, 3.01 mmol) at room temperature, and the mixture stirred for 3 hours at room temperature. The reaction mixture was poured into water (50 mL) and the whole was extracted with diethyl ether (100 mL). The organic layer was washed with water (100 mL×2), brine, dried over MgSO4, and concentrated in vacuo to provide the title product (686 mg, 93% yield)
Cc1c(Br)sc2c1C(=O)CCC2
null
93
null
1,149,327
ord_dataset-b195433d5c354ddfb6cde0d53c41910f
null
2012-01-01T00:04:00
true
[Cl:1][C:2]1[C:3]([NH:28][C:29]2[CH:38]=[CH:37][CH:36]=[CH:35][C:30]=2[C:31]([NH:33][CH3:34])=[O:32])=[N:4][C:5]([NH:8][C:9]2[CH:10]=[C:11]3[C:17](=[CH:18][CH:19]=2)[CH:16]2[CH2:20][CH2:21][CH:12]3[CH2:13][N:14](C(=O)C(F)(F)F)[CH2:15]2)=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+]>CO>[CH:12]12[CH2:21][CH2:20][CH:16]([CH2:15][NH:14][CH2:13]1)[C:17]1[C:11]2=[CH:10][C:9]([NH:8][C:5]2[N:4]=[C:3]([NH:28][C:29]3[CH:38]=[CH:37][CH:36]=[CH:35][C:30]=3[C:31]([NH:33][CH3:34])=[O:32])[C:2]([Cl:1])=[CH:7][N:6]=2)=[CH:19][CH:18]=1
CNC(=O)c1ccccc1Nc1nc(Nc2ccc3c(c2)C2CCC3CN(C(=O)C(F)(F)F)C2)ncc1Cl
null
null
O=C([O-])[O-]
[K+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CO
null
null
null
null
null
null
null
null
null
null
25
48
2-{5-Chloro-2-[10-(2,2,2-trifluoro-acetyl)-10-aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide (402 mg, 0.739 mmol) was dissolved in methanol (30 mL) and potassium carbonate (612 mg, 4.43 mmol, 6.0 eq) was added. The reaction was stirred at room temperature for 48 hours and then concentrated under reduced pressure. Water (10 mL) was added and the product was collected by filtration. 2-[2-(10-Aza-tricyclo[6.3.2.0*2,7*]trideca-2,4,6-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-N-methyl-benzamide was obtained as a yellow solid (330 mg, 99%). m.p. dec. at 230° C.; LCMS (m/e) 449 (M+1); 1H-NMR (CD3OD, 400 MHz) δ 8.68 (d, 1H, J=8.3 Hz), 8.04 (s, 1H), 7.65 (d, 1H, J=7.8 Hz), 7.47-7.39 (m, 2H), 7.33 (dd, 1H, J=2.1 and 7.9 Hz), 7.23-7.17 (m, 1H), 7.16-7.08 (m, 3H), 7.04 (d, 1H, J=7.8 Hz), 3.34 (s, 1H), 3.03-2.98 (m, 1H), 2.97-2.80 (m, 8H), 2.11 (d, 2H, J=8.6 Hz), 1.86-1.79 (m, 2H).
CNC(=O)c1ccccc1Nc1nc(Nc2ccc3c(c2)C2CCC3CNC2)ncc1Cl
null
null
null
1,136,715
ord_dataset-aaeaab5f3720492494c1cbbdd0ed2820
null
2012-01-01T00:02:00
true
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([O:12][CH3:13])=[O:11].[Br:14]N1C(=O)CCC1=O.CC(N=NC(C#N)(C)C)(C#N)C>ClC(Cl)(Cl)Cl>[Br:14][CH:9]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[O:2][CH3:1])[C:10]([O:12][CH3:13])=[O:11]
COC(=O)Cc1ccccc1OC
O=C1CCC(=O)N1Br
null
CC(C)(C#N)N=NC(C)(C)C#N
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
ClC(Cl)(Cl)Cl
null
null
null
null
null
null
null
null
null
null
null
2
A mixture of 14.6 g (81.2 mmol) of methyl (2-methoxyphenyl)acetate, 15.2 g (85.3 mmol) of N-bromosuccinimide and a catalytic amount of AIBN in tetrachloromethane (180 ml) was heated under reflux with stirring for 2 h. The cooled reaction solution was filtered, and the solvent was removed in vacuo. Yield: 21.6 g (100%) of yellow oil
COC(=O)C(Br)c1ccccc1OC
null
null
null
266,832
ord_dataset-a2ae447c4340438c8c3a827109aeb425
null
1993-01-01T00:04:00
true
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.O.C(=O)([O-])[O-].[K+].[K+].Cl.[NH2:20][CH:21]1[CH2:30][CH2:29][C:28]2[CH:27]=[C:26]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:25]=[CH:24][C:23]=2[CH2:22]1>C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:20][CH:21]2[CH2:30][CH2:29][C:28]3[CH:27]=[C:26]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:25]=[CH:24][C:23]=3[CH2:22]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
O=S(=O)(Cl)c1ccc(Cl)cc1
CCOC(=O)Cc1ccc2c(c1)CCC(N)C2
null
Cl
O=C([O-])[O-]
[K+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
O
CCOC(C)=O
null
null
null
null
null
null
null
null
null
25
null
A solution of 1.94 g of 4-chlorophenylsulfonyl chloride in 20 ml of ethyl acetate is added to a mixture of 30 ml of ethyl acetate, 20 ml of water, 3.46 g of potassium carbonate and 2.25 g of ethyl 6-amino-5,6,7,8-tetrahydronaphthalene-2-acetate hydrochloride under stirring at room temperature. After the mixture is stirred at room temperature for 45 minutes, the organic layer is separated therefrom, washed, dried and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform) to give 2.84 g of ethyl 6-(4-chlorophenyl)sulfonylamino-5,6,7,8-tetrahydronaphthalene-2-acetate as oil.
CCOC(=O)Cc1ccc2c(c1)CCC(NS(=O)(=O)c1ccc(Cl)cc1)C2
null
83.5
null
1,070,374
ord_dataset-5df93261afc143c3ae919a57ff4fc1d4
null
2011-01-01T00:07:00
true
[F:1][C:2]([F:14])([F:13])[C:3]1[N:8]=[CH:7][C:6]([S:9](Cl)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[NH2:15][C@@H:16]1[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]1[CH2:22][OH:23].C(N(CC)CC)C>ClCCl>[OH:23][CH2:22][C@@H:17]1[CH2:18][CH2:19][CH2:20][CH2:21][C@H:16]1[NH:15][S:9]([C:6]1[CH:7]=[N:8][C:3]([C:2]([F:14])([F:13])[F:1])=[CH:4][CH:5]=1)(=[O:11])=[O:10]
O=S(=O)(Cl)c1ccc(C(F)(F)F)nc1
N[C@@H]1CCCC[C@H]1CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCN(CC)CC
ClCCl
null
null
null
null
null
null
null
null
null
0
1
A solution of 6-(trifluoromethyl)pyridine-3-sulfonyl chloride (190 mg, 0.78 mmol) in 2 mL dichloromethane was added dropwise to a solution of ((1R,2R)-2-aminocyclohexyl)methanol (100 mg, 0.78 mmol) and triethylamine (320 μL, 2.3 mmol) in 10 mL dichloromethane at 0° C. The reaction was stirred at 0° C. for 1 h, then concentrated and purified by flash chromatography on silica gel with 0 to 60% ethyl acetate in hexane to yield N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)-6-(trifluoromethyl)pyridine-3-sulfonamide (150 mg, 57%). 1H NMR (400 MHz, CDCl3) δ ppm 9.18 (d, J=2.01 Hz, 1H), 8.37 (dd, J=8.06, 1.76 Hz, 1H), 7.83 (d, J=8.31 Hz, 1H), 5.83 (d, J=6.80 Hz, 1H), 3.77 (ddd, J=11.21, 3.78, 3.65 Hz, 1H), 3.36 (dt, J=11.33, 5.67 Hz, 1H), 2.97-3.15 (m, 1H), 2.37 (t, J=5.41 Hz, 1H), 1.73-1.87 (m, 1H), 1.67 (d, J=2.01 Hz, 1H), 1.56-1.66 (m, 2H), 1.33-1.46 (m, 1H), 1.05-1.30 (m, 4H). MS [M+H]+=339. MS [M+Na]+=361.
O=S(=O)(N[C@@H]1CCCC[C@H]1CO)c1ccc(C(F)(F)F)nc1
null
56.8
null
1,535,356
ord_dataset-8d5c200bca27407ab9febe7598e16458
null
2015-01-01T00:01:00
true
FC(F)(F)S(O[C:7]1[C:12]([CH3:13])=[CH:11][C:10]([N+:14]([O-:16])=[O:15])=[CH:9][C:8]=1[CH3:17])(=O)=O.O.[Br-:21].[Li+]>CN(C)C=O.[Cl-].[NH4+]>[Br:21][C:7]1[C:12]([CH3:13])=[CH:11][C:10]([N+:14]([O-:16])=[O:15])=[CH:9][C:8]=1[CH3:17]
Cc1cc([N+](=O)[O-])cc(C)c1OS(=O)(=O)C(F)(F)F
[Br-]
null
[Cl-]
[Li+]
[NH4+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
O
CN(C)C=O
null
null
null
null
null
null
null
null
null
null
null
2,6-dimethyl-4-nitrophenyl trifluoromethanesulfonate (5.0 g, 17 mmol) was dissolved in N,N-dimethylformamide (40 mL). Lithium bromide monohydrate (4.7 g, 45 mmol) was added and the reaction was refluxed overnight. The reaction was diluted with saturated ammonium chloride and the layers were separated. The organics were washed with water (3×40 mL) and brine, dried over sodium sulfate, filtered and concentrated. Purification by column chromatography (2% ethyl acetate in petroleum ether) gave 2-bromo-1,3-dimethyl-5-nitrobenzene (2.7 g, 69%) as a light yellow solid. 1H NMR (400 MHz, CDCl3, δ): 7.94 (s, 2H), 2.50 (s, 6H).
Cc1cc([N+](=O)[O-])cc(C)c1Br
null
69
null
1,485,188
ord_dataset-c3c1091f873b4f40827973a6f1f9b685
null
2014-01-01T00:09:00
true
[F:1][C:2]1[CH:3]=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[CH:19]1(B(O)O)[CH2:21][CH2:20]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1>[CH:19]1([C:4]2[CH:5]=[CH:6][C:7]([N+:8]([O-:10])=[O:9])=[C:2]([F:1])[CH:3]=2)[CH2:21][CH2:20]1
OB(O)C1CC1
O=[N+]([O-])c1ccc(OS(=O)(=O)C(F)(F)F)cc1F
null
O=C([O-])[O-]
[Cs+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
Cc1ccccc1
null
null
null
null
null
null
null
null
null
null
90
null
A stirred suspension of trifluoro-methanesulfonic acid 3-fluoro-4-nitro-phenyl ester (5.6 g, 19 mmol), cyclopropyl boronic acid (2.09 g, 23.3 mmol) Pd(dppf)Cl2 (1.24 g, 1.5 mmol) and 2M aqueous cesium carbonate (30 mL, 60 mmol) in toluene (20 mL) was degassed before being heated at 90° C. under an argon atmosphere for 2.5 hours. The reaction mixture was allowed to cool to room temperature before filtering through a pad of Celite®, washing with ethyl acetate. The filtrate was washed (water, brine), and then dried (MgSO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0-30% ethyl acetate in pentane) to give the title compound as a yellow solid (2.79 g, 81%). 1H NMR (DMSO-d6, 400 MHz) 8.03 (1 H, t, J=8.39 Hz), 7.28 (1 H, dd, J=13.19, 1.91 Hz), 7.16 (1 H, dd, J=8.61, 1.90 Hz), 2.14-2.05 (1 H, m), 1.21-1.05 (2 H, m), 0.92-0.82 (2 H, m).
O=[N+]([O-])c1ccc(C2CC2)cc1F
null
81.1
null
1,419,406
ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f
null
2014-01-01T00:04:00
true
[NH2:1][C:2]1[C:7]([C:8](=[O:10])[NH2:9])=[CH:6][C:5]([Cl:11])=[CH:4][C:3]=1[NH:12][C:13]([C:15]1[CH:20]=[CH:19][C:18]([CH:21]2[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]2)=[CH:17][CH:16]=1)=O>C(O)(=O)C>[Cl:11][C:5]1[CH:6]=[C:7]([C:8]([NH2:9])=[O:10])[C:2]2[N:1]=[C:13]([C:15]3[CH:16]=[CH:17][C:18]([CH:21]4[CH2:22][CH2:23][NH:24][CH2:25][CH2:26]4)=[CH:19][CH:20]=3)[NH:12][C:3]=2[CH:4]=1
CC(C)(C)OC(=O)N1CCC(c2ccc(C(=O)Nc3cc(Cl)cc(C(N)=O)c3N)cc2)CC1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CC(=O)O
null
null
null
null
null
null
null
null
null
null
null
1
A solution of EXAMPLE 74A (60 mg) in acetic acid (5 mL) at reflux was stirred for 60 minutes and concentrated. The concentrate was purified by chromatography on silica gel with 10% methanol/dichloromethane. 1H NMR (DMSO-d6) δ 9.24 (s, 1H), 8.22 (d, J=7.98 Hz, 2H), 7.96 (s, 1H), 7.75-7.84 (m, 2H), 7.46 (d, J=8.29 Hz, 2H), 3.41 (d, J=12.27 Hz, 2H), 2.99-3.08 (m, 2H), 2.96 (t, J=3.53 Hz, 1H), 2.01 (d, J=12.27 Hz, 2H), 1.79-1.90 (m, 2H).
NC(=O)c1cc(Cl)cc2[nH]c(-c3ccc(C4CCNCC4)cc3)nc12
null
null
null
243,359
ord_dataset-fa3b512e2d924b9b965301ebcba6853d
null
1992-01-01T00:03:00
true
[CH3:1][C:2]1[N:3]([C:8]2[CH:13]=[CH:12][C:11](/[CH:14]=[CH:15]/[C:16]([OH:18])=[O:17])=[CH:10][CH:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1>C(OCC)(=O)C.[Pd]>[CH3:7][C:4]1[N:3]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]([OH:18])=[O:17])=[CH:10][CH:9]=2)[C:2]([CH3:1])=[CH:6][CH:5]=1
Cc1ccc(C)n1-c1ccc(/C=C/C(=O)O)cc1
null
null
[Pd]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCOC(C)=O
null
null
null
null
null
null
null
null
null
null
null
null
A solution of (E)-3-[4-(2,5-dimethyl-1H-pyrrol-1-yl)-phenyl]-2-propenoic acid in ethyl acetate is hydrogenated at 3 atmospheres pressure using 10% palladium on charcoal to yield 3-[4-(2,5-dimethyl-1H-pyrrol-1-yl)-phenyl]-propanoic acid, as an oil.
Cc1ccc(C)n1-c1ccc(CCC(=O)O)cc1
null
null
null
241,293
ord_dataset-685186618e9f4e7aaa72ac40c16ef354
null
1992-01-01T00:01:00
true
[C:1]([NH:9][C:10]([NH:12][C:13]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:14]=1[C:15]([NH2:17])=[O:16])=S)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N.OO>CO>[CH3:22][C:19]1[CH:18]=[C:14]2[C:13](=[CH:21][CH:20]=1)[NH:12][C:10]([NH:9][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[N:17][C:15]2=[O:16]
Cc1ccc(NC(=S)NC(=O)c2ccccc2)c(C(N)=O)c1
null
null
N
OO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CO
null
null
null
null
null
null
null
null
null
null
null
8
To a stirred mixture of 6 g of the above benzamide, 100 ml of methanolic ammonia and 200 ml of methanol was added dropwise, in increments, 20 ml of 30% hydrogen peroxide. After stirring overnight, the solid was collected, partially dissolved in 500 ml of hot acetonitrile and filtered. The filtrate was chilled, giving 1.2 g of the desired product as white crystals, mp 240°-242° C.
Cc1ccc2[nH]c(NC(=O)c3ccccc3)nc(=O)c2c1
null
22.4
null
948,074
ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8
null
2010-01-01T00:04:00
true
[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])[CH:5]=[CH:4][C:3]=1[CH2:15][C:16]([C:18]1[N:22]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[N:21]=[C:20]([C:31]#[N:32])[CH:19]=1)=[O:17].S(O)(O)(=O)=[O:34].C(OCC)(=O)C>O>[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]2=[O:14])[CH:5]=[CH:4][C:3]=1[CH2:15][C:16]([C:18]1[N:22]([C:23]2[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)[N:21]=[C:20]([C:31]([NH2:32])=[O:34])[CH:19]=1)=[O:17]
O=S(=O)(O)O
COc1ccc(-n2nc(C#N)cc2C(=O)Cc2ccc(-n3ccccc3=O)cc2F)cc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCOC(C)=O
O
null
null
null
null
null
null
null
null
null
null
2
Part I. To 5-{[2-fluoro-4-(2-oxo-1(2H)-pyridinyl)-phenyl]acetyl}-1-(4-methoxyphenyl)-1H-pyrazole-3-carbonitrile (75 mg, 0.175 mmol) was added concentrated aqueous dihydrogen sulfate (4.5 mL). After 2 h, the reaction was poured into ethyl acetate (50 mL) and water (50 mL), and the layers were separated. The organic layer was washed with saturated aqueous sodium chloride (50 mL), dried over sodium sulfate, and concentrated to dryness. The resulting residue was purified by radial chromatography (2% methyl alcohol in dichloromethane) to afford 5-{[2-fluoro-4-(2-oxo-1(2H)-pyridinyl)phenyl]acetyl}-1-(4-methoxyphenyl)-1H-pyrazole-3-carboxamide (32 mg, 41%) as a white solid upon lyophilization from 10% acetonitrile in water. LC/MS (ESI+): 448.2 (M+H)+. 1H NMR (CD3OD) δ 7.70 (s, 1H), 7.60 (m, 2H), 7.43 (t, 1H), 7.16-7.32 (m, 4H), 6.97 (d, 2H), 6.60 (d, 1H), 6.45 (t, 1H), 4.40 (s, 2H), 3.83 (s, 3H).
COc1ccc(-n2nc(C(N)=O)cc2C(=O)Cc2ccc(-n3ccccc3=O)cc2F)cc1
null
41
null
730,727
ord_dataset-eb4226b4f7644a01a737e7547b70014a
null
2006-01-01T00:09:00
true
Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([F:14])=[C:10]([I:13])[CH:11]=2)[N:6]=[CH:5][N:4]=1.O1CCOCC1.Cl.[CH2:22]([O:29][C:30]1[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>ClCCl>[ClH:2].[CH2:22]([O:29][C:30]1[CH:31]=[CH:32][C:33]([NH:34][C:3]2[C:12]3[C:7](=[CH:8][C:9]([F:14])=[C:10]([I:13])[CH:11]=3)[N:6]=[CH:5][N:4]=2)=[CH:35][CH:36]=1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Fc1cc2ncnc(Cl)c2cc1I
Nc1ccc(OCc2ccccc2)cc1
null
Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1COCCO1
ClCCl
null
null
null
null
null
null
null
null
null
110
null
Prepared according to Procedure A from 4-chloro-6-iodo-7-fluoro-quinazoline hydrochloride (4.02 grams, 11.65 mmoles), anhydrous dioxane (70 ml), dichloromethane (20 ml), and 4-benzyloxyaniline hydrochloride (2.83 grams, 12 mmoles). The mixture was stirred and heated to 110° C. (oil bath temperature) for 16 hours, cooled to room temperature and filtered to remove the precipitated solids. The solids were washed with cold anhydrous dioxane (100 ml) followed by cold anhydrous diethyl ether. The yellowish solid was collected and dried under vacuum at room temperature to yield 4.68 grams (79%) of the title compound. δH NMR (400 MHz, DMSO-d6): 11.2(s, 1H), 9.3(d, 1H), 8.79(s, 1H), 7.64(d, 1H), 7.58(d, 2H), 7.44(d, 2H), 7.38(m, 2H), 7.31(m, 1H), 7.09(d, 2H), 5.14(s, 2H) ESI-MS m/z 472(M+1).
Fc1cc2ncnc(Nc3ccc(OCc4ccccc4)cc3)c2cc1I
null
79.1
null
682,701
ord_dataset-359b8fc87f4244be89d6f02bc5036eac
null
2005-01-01T00:09:00
true
[Cl:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][N:5]([C:11]1[C:16]([C:17]([F:20])([F:19])[F:18])=[CH:15][C:14]([NH2:21])=[CH:13][C:12]=1[NH2:22])[C:6](=[O:10])OCC.[H-].[Na+].C(=O)(O)[O-].[Na+]>C(O)C>[NH2:21][C:14]1[CH:15]=[C:16]([C:17]([F:18])([F:20])[F:19])[C:11]2[N:5]([CH2:4][C:3]3[CH:23]=[CH:24][CH:25]=[CH:26][C:2]=3[Cl:1])[C:6](=[O:10])[NH:22][C:12]=2[CH:13]=1
CCOC(=O)N(Cc1ccccc1Cl)c1c(N)cc(N)cc1C(F)(F)F
null
null
O=C([O-])O
[H-]
[Na+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCO
null
null
null
null
null
null
null
null
null
null
null
null
Ethyl 2-chlorobenzyl[2,4-diamino-6-(trifluoromethyl)phenyl]carbamate (85.6 mg) was dissolved in ethanol (10 ml), and to the solution was added sodium hydride (17.7 mg). The reaction mixture was heated at reflux for 24 hours. After allowing to cool, to the reaction mixture was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted 4 times with chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resultant residue was purified by preparative TLC (2 mm, 20×20 cm, CHCl3-methanol=5:1) to give the title compound (46.0 mg).
Nc1cc(C(F)(F)F)c2c(c1)[nH]c(=O)n2Cc1ccccc1Cl
null
61
null
170,111
ord_dataset-37d3220f708c49ad839bab296b722248
null
1988-01-01T00:03:00
true
[OH:1][C:2]1[CH:15]=[CH:14][C:13]([OH:16])=[C:12]2[C:3]=1[C:4](=[O:84])[C:5]1[C:6]([NH:51][CH2:52][CH2:53][NH:54][C:55](=[O:83])[C@H:56]([CH2:79][CH:80]([CH3:82])[CH3:81])[NH:57][C:58](=[O:78])[C@H:59]([CH2:71][C:72]3[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=3)[NH:60]C(OCC3C=CC=CC=3)=O)=[CH:7][CH:8]=[C:9]([NH:18][CH2:19][CH2:20][NH:21][C:22](=[O:50])[C@H:23]([CH2:46][CH:47]([CH3:49])[CH3:48])[NH:24][C:25](=[O:45])[C@H:26]([CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[NH:27]C(OCC3C=CC=CC=3)=O)[C:10]=1[C:11]2=[O:17].[BrH:85]>C(O)(=O)C>[BrH:85].[BrH:85].[OH:1][C:2]1[CH:15]=[CH:14][C:13]([OH:16])=[C:12]2[C:3]=1[C:4](=[O:84])[C:5]1[C:6]([NH:51][CH2:52][CH2:53][NH:54][C:55](=[O:83])[C@H:56]([CH2:79][CH:80]([CH3:82])[CH3:81])[NH:57][C:58](=[O:78])[C@H:59]([CH2:71][C:72]3[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=3)[NH2:60])=[CH:7][CH:8]=[C:9]([NH:18][CH2:19][CH2:20][NH:21][C:22](=[O:50])[C@H:23]([CH2:46][CH:47]([CH3:49])[CH3:48])[NH:24][C:25](=[O:45])[C@H:26]([CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[NH2:27])[C:10]=1[C:11]2=[O:17]
CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1)C(=O)NCCNc1ccc(NCCNC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc2ccccc2)NC(=O)OCc2ccccc2)c2c1C(=O)c1c(O)ccc(O)c1C2=O
null
null
Br
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CC(=O)O
null
null
null
null
null
null
null
null
null
null
null
null
A 2.75 g portion of N,N'-[(9,10-dihydro-5,8-dihydroxy-9,10-dioxo-1,4-anthracenediyl)bis(imino-2,1-ethanediyl)]bis[N-[(phenylmethoxy)carbonyl]-L-phenylalanyl-L-leucinamide] was reacted by a modification of the procedure of Example 31, by being dissolved in 75 ml of glacial acetic acid previously saturated for 5 minutes with anhydrous hydrogen bromide. The mixture was reacted for 2.5 hours, then more hydrogen bromide was bubbled into the solution for 15 minutes and after another 2 hours the solid was collected, giving 2.7 g of the desired product, mp 180° C. (dec.).
CC(C)C[C@H](NC(=O)[C@@H](N)Cc1ccccc1)C(=O)NCCNc1ccc(NCCNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)Cc2ccccc2)c2c1C(=O)c1c(O)ccc(O)c1C2=O
null
null
null
234,371
ord_dataset-45d20d09e4d64f45bdd419044025b4d3
null
1991-01-01T00:09:00
true
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[CH2:15][C@H:14]([CH2:16][OH:17])[CH:13]=[CH:12]2)=[C:4](Cl)[N:3]=1.[CH2:19]([NH2:21])[CH3:20].[OH-].[Na+]>>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[CH2:15][C@H:14]([CH2:16][OH:17])[CH:13]=[CH:12]2)=[C:4]([NH:21][CH2:19][CH3:20])[N:3]=1
CCN
Nc1nc(Cl)c2ncn([C@H]3C=C[C@@H](CO)C3)c2n1
null
[Na+]
[OH-]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
80
null
(±)-cis-4-(2-Amino-6-chloro-9H-purin-9-yl)-2-cyclopentene-1-methanol (0.544g, 2 mmol) was added to an ethyl amine-saturated methanol solution (14 mL). The solution was heated at 80° C. in a Parr bomb for 2.5 hours. 1 N NaOH (2 mL) was added, and solvent evaporated. The residual oil was chromatographed on silica gel. Title compound was eluted with 10% methanol-chloroform; white crystals after crystallization from acetonitrile-methanol (0.365 g, 67%); mp 171-173° C.;
CCNc1nc(N)nc2c1ncn2[C@H]1C=C[C@@H](CO)C1
null
null
null
549,756
ord_dataset-e967d076b4894c2c854795f019ed3c39
null
2002-01-01T00:06:00
true
C(OC1C=C([C@H:25]2[CH2:29][CH2:28][C@H:27]([C:30]3[CH:35]=[C:34]([O:36][CH3:37])[C:33]([O:38][CH3:39])=[C:32]([O:40][CH3:41])[CH:31]=3)[O:26]2)C=C(S(CCC)(=O)=O)C=1OCCC)C1C=CC=CC=1>C(OCC)(=O)C>[CH3:41][O:40][C:32]1[CH:31]=[C:30]([CH:27]2[CH2:28][CH2:29][CH2:25][O:26]2)[CH:35]=[C:34]([O:36][CH3:37])[C:33]=1[O:38][CH3:39]
CCCOc1c(OCc2ccccc2)cc([C@H]2CC[C@H](c3cc(OC)c(OC)c(OC)c3)O2)cc1S(=O)(=O)CCC
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCOC(C)=O
null
null
null
null
null
null
null
null
null
null
25
2
To a solution of (±)-trans-2-(3-benzyloxy-4-propoxy-5-propylsulfonylphenyl)-5-(3,4,5-trimethoxyphenyl) tetrahydrofuran (6.35 g, 10.87 mol) in ethyl acetate (50 ml) was added 10% pd/c (0.80 g). The reaction mixture was stirred at room temperature under balloon pressure for 2 h. The Pd/C was filtered through celite and washed with ethyl acetate (80 ml). The filtrate was concentrated and the crude product was purified through silica gel column using Ethyl acetate:light petroleum (1:3) to give (±)-trans-2-(3-hydroxy-4-propoxy-5-propylsulfonylphenyl)-5-(3,4,5-trimethoxyphenyl tetrahydrofuran as a solid (3.30 g, 61%). TLC: Ethyl acetate:light petroleum (3:2), Rf=0.5 ; m.p. 115-117° C.; 1H NMR (CDCl3, 200 MHz): δ 0.95 (t, J=7.72 Hz, 3H), 1.0 (t, J=6.81 Hz, 3H), 1.6-1.95 (m, 6H), 2.3-2.42 (m, 2H), 3.25 (m, 2H), 3.75 (s, 3H), 3.80 (s, 6H), 4.03 (t, J=6.12 Hz, 2H), 5.0-5.13 (m, 2H), 6.28 (s, 1H), 6.5 (s, 2H), 7.18 (d, J=1.54 Hz, 1H), 7.34 (d, J=1.54 Hz, 1H); IR (neat): 3400, 2975, 2945, 2860, 1725, 1540, 1490, 1440 cm−1. FAB Mass: 495 (M+), HRMS:calculated 0.495.205265; found. 495.207215.
COc1cc(C2CCCO2)cc(OC)c1OC
null
0.1
null
1,446,735
ord_dataset-a86112d52cd54525a5e36d41f18aced2
null
2014-01-01T00:07:00
true
C[O:2][C:3](=[O:21])[CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[O:12][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH3:20])=[N:10][CH:9]=1.C1COCC1.[OH-].[Na+]>CCO>[CH3:20][O:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C:11]1[O:12][C:8]([CH2:7][CH2:6][CH2:5][CH2:4][C:3]([OH:21])=[O:2])=[CH:9][N:10]=1
COC(=O)CCCCc1cnc(-c2ccccc2OC)o1
null
null
[Na+]
[OH-]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCO
C1CCOC1
null
null
null
null
null
null
null
null
null
null
null
Combine 5-[2-(2-methoxy-phenyl)-oxazol-5-yl]-pentanoic acid methyl ester (2.1 g, 7.3 mmol) with THF (4 mL), EtOH (4 mL) and 2N NaOH (15 mL) and stir until hydrolysis is complete. Concentrate the mixture, dilute the residue with water and adjust the pH to 3.0-4.0 using aq HCl. Extract the mixture with CH2Cl2 and concentrate the extracts in vacuo. Drying gives 5-[2-(2-methoxy-phenyl)-oxazol-5-yl]-pentanoic acid (1.8 g, 91%). MS (ES): (M+1)+ 274.1, 275.1 m/z.
COc1ccccc1-c1ncc(CCCCC(=O)O)o1
null
89.6
null
491,127
ord_dataset-37b0416f244344a08cf357e851eedf2a
null
2001-01-01T00:01:00
true
[CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][N:7]=1)=[O:5])[CH3:2].[H][H]>FC(F)(F)C(O)=O.[Pt]=O>[CH2:1]([O:3][C:4]([C:6]1[C:15](=[O:16])[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[NH:8][N:7]=1)=[O:5])[CH3:2]
CCOC(=O)c1n[nH]c2ccccc2c1=O
[H][H]
null
O=[Pt]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
O=C(O)C(F)(F)F
null
null
null
null
null
null
null
null
null
null
null
null
To 4-oxo-1,4-dihydrocinnoline-3-carboxylic acid ethyl ester (4.5 g) dissolved in trifluoroacetic acid (20 ml) was added platinum oxide (0.2 g). The reaction mixture was hydrogenated at 50 psi until no further uptake of hydrogen was observed. The catalyst was collected by filtration, the filtrate was poured onto ice, the pH was raised to pH6 with base, the resulting precipitate was collected by filtration, washed with water and dried to give a solid (2.8 g, 61%). δH (250 MHz; DMSO-d6) 1.26 (3H, t, J=7 Hz, CH3), 1.68 (4H, m, CH2), 2.33 (2H, t, J=5.5 Hz, CH2), 2.62 (2H, t, J=5.5 Hz, CH2), 4.25 (2H, t, J=7 Hz, CH2), 13.19 (1H, br s, NH), m/z (ESP+) 223 (MH+).
CCOC(=O)c1n[nH]c2c(c1=O)CCCC2
null
61.1
null
667,762
ord_dataset-c5ee194443334d3e92aff17e46e33bd1
null
2005-01-01T00:04:00
true
[F:1][C:2]([F:14])([F:13])[C:3]1[C:8]2[CH:9]=[CH:10][O:11][C:7]=2[C:6](Br)=[CH:5][CH:4]=1.[CH2:15]([N:22]1[CH2:27][CH2:26][C:25](=[O:28])[CH:24]([CH3:29])[CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[CH2:15]([N:22]1[CH2:27][CH2:26][C:25]([OH:28])([C:6]2[C:7]3[O:11][CH:10]=[CH:9][C:8]=3[C:3]([C:2]([F:14])([F:13])[F:1])=[CH:4][CH:5]=2)[CH:24]([CH3:29])[CH2:23]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
CC1CN(Cc2ccccc2)CCC1=O
FC(F)(F)c1ccc(Br)c2occc12
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
Beginning with 1.5 gm (5.7 mMol) 4-trifluoromethyl-7-bromobenzofuran and 1.26 gm (6.2 mMol) 1-benzyl-3-methyl-4-oxopiperidine, 0.85 gm (39%) of the desired compound were recovered essentially as described in EXAMPLE 3.
CC1CN(Cc2ccccc2)CCC1(O)c1ccc(C(F)(F)F)c2ccoc12
null
38.3
null
1,746,192
ord_dataset-60a3e71da3174666a50a61dcfa611a9f
null
2016-01-01T00:07:00
true
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1Br.[CH2:29]([O:31][C:32]1[C:37]([NH:38][S:39]([C:42]2[CH:47]=[CH:46][C:45]([OH:48])=[C:44]([CH3:49])[CH:43]=2)(=[O:41])=[O:40])=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][N:33]=1)[CH3:30].C(=O)([O-])[O-].[Cs+].[Cs+]>>[NH2:1][C:2]1[C:3]([C:35]2[CH:36]=[C:37]([NH:38][S:39]([C:42]3[CH:47]=[CH:46][C:45]([OH:48])=[C:44]([CH3:49])[CH:43]=3)(=[O:41])=[O:40])[C:32]([O:31][CH2:29][CH3:30])=[N:33][CH:34]=2)=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24]([CH3:27])[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[N:5]=[CH:6][N:7]=1
CCOc1ncc(B2OC(C)(C)C(C)(C)O2)cc1NS(=O)(=O)c1ccc(O)c(C)c1
Cc1ccn2nc([C@H](C)Nc3ncnc(N)c3Br)n(-c3ccccc3)c(=O)c12
null
O=C([O-])[O-]
[Cs+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
(S)-2-(1-((6-Amino-5-bromopyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (100 mg, 0.23 mmol) was treated with N-(2-ethoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-4-hydroxy-3-methylbenzenesulfonamide (149 mg, 0.34 mmol), 2M cesium carbonate (340 μl, 0.68 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (19 mg, 0.02 mmol) according to the method described in Example 3 to give 47 mg (27% yield) of the title compound. Purity 85%.
CCOc1ncc(-c2c(N)ncnc2N[C@@H](C)c2nn3ccc(C)c3c(=O)n2-c2ccccc2)cc1NS(=O)(=O)c1ccc(O)c(C)c1
null
30.6
null
832,180
ord_dataset-47bd90bf5ec74fcd99ce250a56e18c8f
null
2008-01-01T00:07:00
true
[O:1]([C@@H:9]1[C@@H:16]2[N:12]([C:13](=[O:28])[N:14]([C:18]3[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[C:20]([Cl:26])[C:19]=3[CH3:27])[C@H:15]2[CH3:17])[CH2:11][CH2:10]1)[Si](C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[OH:1][C@@H:9]1[C@@H:16]2[N:12]([C:13](=[O:28])[N:14]([C:18]3[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[C:20]([Cl:26])[C:19]=3[CH3:27])[C@H:15]2[CH3:17])[CH2:11][CH2:10]1
Cc1c(N2C(=O)N3CC[C@H](O[Si](C)(C)C(C)(C)C)[C@H]3[C@@H]2C)ccc(C#N)c1Cl
null
null
CCCC[N+](CCCC)(CCCC)CCCC
[F-]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1CCOC1
null
null
null
null
null
null
null
null
null
null
25
1
To a solution of 61J (369 mg) in THF (4 mL) was added TBAF (1.0 M in THF, 1.3 mL). The reaction was stirred at rt for 1 h. The reaction was extracted with EtOAc which was washed three times with water, dried over MgSO4, filtered and concentrated. Purification by reverse phase HPLC (Phenoenex Luna 20×100 mm S5 C18, 10 min. grad, 20 mL/min, 20-100% B solvent, A=10% MeOH/water+0.1% TFA, B=90% MeOH/Water+0.1% TFA) provided the title compound (186 mg): MS (ES) m/z 306.42 [M+H]+
Cc1c(N2C(=O)N3CC[C@H](O)[C@H]3[C@@H]2C)ccc(C#N)c1Cl
null
69.2
null
1,304,615
ord_dataset-78c3f723155a4347a902b53bcee1524d
null
2013-01-01T00:06:00
true
[CH2:1]([O:8][CH2:9][C:10]([N:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:18][C:19]1[CH:24]=[C:23]([CH2:25]Cl)[CH:22]=[CH:21][N:20]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:18][C:19]1[CH:24]=[C:23]([CH2:25][N:15]2[CH2:14][CH2:13][N:12]([C:10](=[O:11])[CH2:9][O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:17][CH2:16]2)[CH:22]=[CH:21][N:20]=1
ClCc1ccnc(Cl)c1
O=C(COCc1ccccc1)N1CCNCC1
null
O=C([O-])[O-]
[K+]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CN(C)C=O
null
null
null
null
null
null
null
null
null
null
25
1
N-Benzyloxyacetyl-piperazine (1.0 equiv) was mixed with the compound 2-chloro-4-(chloro-methyl)pyridine (1.0 equiv) and K2CO3 (4 equiv) in DMF. The mixture was stirred for 1 h at rt. After removing most of the solvent, the residue was partitioned in water and EtOAc. The organic layer was separated, dried over anhydrous Na2SO4, and evaporated in vacuo. The residue was purified by flash chromatography to give the title compound as a solid.
O=C(COCc1ccccc1)N1CCN(Cc2ccnc(Cl)c2)CC1
null
null
null
1,349,469
ord_dataset-6034127657614f02860ed057b62b882e
null
2013-01-01T00:10:00
true
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]([CH3:13])([CH3:12])[CH2:10][CH2:9][CH2:8][N:7]([C:14](=[O:16])[CH3:15])[C:6]=2[CH:17]=1.Cl[C:19]1[N:24]=[C:23]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[CH:28][C:27]=2[O:38][CH3:39])[C:22]([Cl:40])=[CH:21][N:20]=1>>[Cl:40][C:22]1[C:23]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([N:32]3[CH2:33][CH2:34][O:35][CH2:36][CH2:37]3)=[CH:28][C:27]=2[O:38][CH3:39])=[N:24][C:19]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[C:11]([CH3:13])([CH3:12])[CH2:10][CH2:9][CH2:8][N:7]([C:14](=[O:16])[CH3:15])[C:6]=3[CH:17]=2)=[N:20][CH:21]=1
CC(=O)N1CCCC(C)(C)c2ccc(N)cc21
COc1cc(N2CCOCC2)ccc1Nc1nc(Cl)ncc1Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
The title compound was prepared with a procedure analogous to that used to prepare example 381 by combining 1-(8-Amino-5,5-dimethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl)-ethanone and (2,5-Dichloro-pyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine to yield an off-white solid (93%). LCMS: m/z=551.54 (M+H+), 1H NMR (400 MHz, CDCl3) δ 8.12 (d, 1H, J=8.6 Hz), 8.01 (s, 1H), 7.54 (s, 1H), 7.45 (s, 1H), 7.41 (d, 1H, J=1.5 Hz), 7.32 (m, 2H), 6.53 (m, 2H), 4.74 (m, 1H), 3.89 (m, 7H), 3.17 (m, 4H), 2.60 (m, 1H), 2.20 (m, 1H), 1.91 (s, 3H), 1.62 (m, 3H), 1.41 (s, 3H), 1.19 (s, 3H).
COc1cc(N2CCOCC2)ccc1Nc1nc(Nc2ccc3c(c2)N(C(C)=O)CCCC3(C)C)ncc1Cl
null
null
null
1,643,382
ord_dataset-bcc0b01d4f58457a8733b10a099f43ba
null
2015-01-01T00:10:00
true
FC(F)(F)S(O[CH2:7][C@H:8]([CH3:11])[CH2:9][F:10])(=O)=O.[CH3:14][C@H:15]1[NH:27][C@H:26]([C:28]2[CH:33]=[CH:32][C:31](/[CH:34]=[CH:35]/[C:36]([O:38][CH3:39])=[O:37])=[CH:30][CH:29]=2)[C:18]2[NH:19][C:20]3[C:25]([C:17]=2[CH2:16]1)=[CH:24][CH:23]=[CH:22][CH:21]=3.C(N(CC)C(C)C)(C)C>O1CCOCC1>[F:10][CH2:9][C@@H:8]([CH3:11])[CH2:7][N:27]1[C@H:15]([CH3:14])[CH2:16][C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[NH:19][C:18]=2[C@H:26]1[C:28]1[CH:29]=[CH:30][C:31](/[CH:34]=[CH:35]/[C:36]([O:38][CH3:39])=[O:37])=[CH:32][CH:33]=1
COC(=O)/C=C/c1ccc([C@H]2N[C@H](C)Cc3c2[nH]c2ccccc32)cc1
C[C@H](CF)COS(=O)(=O)C(F)(F)F
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
C1COCCO1
CCN(C(C)C)C(C)C
null
null
null
null
null
null
null
null
null
90
1
(S)-3-Fluoro-2-methylpropyl trifluoromethanesulfonate (obtained as described in Example 3, preparation of starting materials) (291 mg, 1.30 mmol) was added to a solution of (E)-methyl 3-(4-((1R,3R)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylate (300 mg, 0.87 mmol) and N,N-diisopropylethylamine (0.226 ml, 1.30 mmol) in 1,4-dioxane (5 ml). The mixture was stirred at 90° C. for 1 hour then the mixture was evaporated to dryness and the residue was partitioned between DCM (30 nil) and water (30 ml). The aqueous layer was extracted with DCM (30 ml) and the extracts combined with the organic layer. The combined extracts were filtered through a phase-separating paper and evaporated. The residue was purified by flash silica chromatography, elution solvent 15% EtOAc in heptane. Pure fractions were evaporated to dryness to afford (E)-methyl 3-(4-((1R,3R)-2-((S)-3-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylate (314 mg, 86%) as an off-white solid. 1H NMR (400 MHz, DMSO, 30° C.) δ 0.87 (3H, d), 1.06 (3H, d), 1.9-2.28 (2H, m), 2.55-2.8 (3H, m), 2.97-3.21 (1H, m), 3.72 (3H, s), 4.31-4.69 (2H, m), 4.88 (1H, s), 6.60 (1H, dd), 6.98 (1H, t), 7.04 (1H, t), 7.17-7.35 (3H, m), 7.44 (1H, d), 7.55-7.76 (3H, m), 10.65 (1H, s). m/z: ES+ [M+H]+ 421.
COC(=O)/C=C/c1ccc([C@@H]2c3[nH]c4ccccc4c3C[C@@H](C)N2C[C@H](C)CF)cc1
null
85.8
null
850,293
ord_dataset-171b840ae6e84e45bab43b987d09f5c7
null
2008-01-01T00:11:00
true
C[OH:2].[CH2:3]([O:10][CH:11]1[CH2:16][CH2:15][CH:14]([O:17][CH2:18][C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=C)[CH:13]([F:27])[CH2:12]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH2:3]([O:10][CH:11]1[CH2:16][CH2:15][CH:14]([O:17][CH2:18][C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:2])[CH:13]([F:27])[CH2:12]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
C=C(COC1CCC(OCc2ccccc2)CC1F)c1ccccc1
CO
null
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
ClCCl
null
null
null
null
null
null
null
null
null
null
25
null
A methanol (300 mL) solution of [1-({[4-(Benzyloxy)-2-fluorocyclohexyl]oxy}methyl)vinyl]benzene (2.02 g, 5.95 mmol) was cooled to −70° C. Ozone gas was bubbled through the solution until a blue color appeared. The solution was purged with nitrogen then a solution of triphenylphosphine (2.34 g, 8.92 mmol) in methylene chloride (100 mL) was added. Contents of the reaction flask were warmed to room temperature and the solvent was removed under reduced pressure. The remaining residue was subjected to flash column chromatography (hexane:ethyl acetate, 90:10) to give 2-{[4-(Benzyloxy)-2-fluorocyclohexyl]oxy}-1-phenylethanone as a colorless oil (1.68 g, 83% yield).
O=C(COC1CCC(OCc2ccccc2)CC1F)c1ccccc1
null
83
null
352,754
ord_dataset-127eb5fdd5b4402e92b51d0b55a5dcb5
null
1997-01-01T00:01:00
true
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[F:15][C:16]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:17]=1[CH2:18][CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][CH2:12][C@H:11]([N:22]3[CH2:21][CH2:20][CH:19]([CH2:18][C:17]4[CH:25]=[C:26]([F:29])[CH:27]=[CH:28][C:16]=4[F:15])[CH2:24][CH2:23]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
O=C1CCC(c2ccc(F)cc2)CC1
Fc1ccc(F)c(CC2CCNCC2)c1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
4-(4-Fluorophenyl)cyclohexanone and 4-(2,5-difluorobenzyl)piperidine were reacted as described in example 9 to give the product (36%, mp: 80°-81° C.). Calc'd for C24H28F3N: C, 74.40%; H, 7.29%; N, 3.18%. Found: C, 74.25%; H, 7.29%; N, 3.56%.
Fc1ccc([C@H]2CC[C@H](N3CCC(Cc4cc(F)ccc4F)CC3)CC2)cc1
null
null
null
183,242
ord_dataset-f25e1b7f8ef54305a5170f5395a768c7
null
1989-01-01T00:01:00
true
C([O:4][C:5]1[CH:6]=[C:7]([CH:19]=[CH:20][C:21]=1[O:22]C(=O)C)[C:8]([N:10]1[CH2:14][CH2:13][N:12]([C:15]([NH2:17])=[O:16])[C:11]1=[O:18])=[O:9])(=O)C.N>C(O)C.O>[OH:4][C:5]1[CH:6]=[C:7]([CH:19]=[CH:20][C:21]=1[OH:22])[C:8]([N:10]1[CH2:14][CH2:13][N:12]([C:15]([NH2:17])=[O:16])[C:11]1=[O:18])=[O:9]
CC(=O)Oc1ccc(C(=O)N2CCN(C(N)=O)C2=O)cc1OC(C)=O
null
null
N
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
CCO
O
null
null
null
null
null
null
null
null
null
null
0.17
To a suspension of 6.2 g (0.017 mol) of 3-[3,4-bis(acetyloxy)benzoyl]-2-oxo-1-imidazolidinecarboxamide in 50 ml of a 1:1 mixture of ethanol/water was added dropwise 2.1 ml of ammonia. After stirring for 10 minutes, a clear solution formed from which 3-(3,4-dihydroxybenzoyl)-2-oxo-1-imidazolidinecarboxamide began to crystallize after 15 minutes, yielding 3.8 g.
NC(=O)N1CCN(C(=O)c2ccc(O)c(O)c2)C1=O
null
null
null
369,795
ord_dataset-15cdba4c7f064b3f9cd7343cb3187881
null
1997-01-01T00:07:00
true
O=[CH:2][CH2:3][CH:4]1[C:12]([CH2:15][CH3:16])([CH2:13][CH3:14])[C:11]2[C:6](=[CH:7][C:8]([O:17][CH3:18])=[CH:9][CH:10]=2)[C:5]1=O.O.[NH2:21][CH2:22][C@H:23]([OH:25])[CH3:24]>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:18][O:17][C:8]1[CH:7]=[C:6]2[C:11]([C:12]([CH2:15][CH3:16])([CH2:13][CH3:14])[C:4]3[CH:3]=[CH:2][N:21]([CH2:22][C@H:23]([OH:25])[CH3:24])[C:5]=32)=[CH:10][CH:9]=1
CCC1(CC)c2ccc(OC)cc2C(=O)C1CC=O
C[C@@H](O)CN
null
Cc1ccc(S(=O)(=O)O)cc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
Cc1ccccc1
O
null
null
null
null
null
null
null
null
null
null
0.75
A solution of 3.9 g of (RS)-2-(2-oxoethyl)-6-methoxy-3,3-diethyl-1-indanone and 120 mg of p-toluenesulfonic acid in 100 ml of anhydrous toluene was heated on a water separator. A solution of 4.5 g of (R)-1-amino-2-propanol in 30 ml of anhydrous toluene was added dropwise to the boiling solution over a period of 5 minutes. Subsequently, the mixture was boiled for an additional 45 minutes, during which the solvent was reduced to a volume of 20 ml. The cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/hexane 1:1). 2.73 g (61%) of (R)-1-(7-methoxy-4,4-diethyl-1,4-dihydro-indeno[1,2-b]pyrrol-1-yl)-propan-2-ol were obtained as a red-brown oil.
CCC1(CC)c2ccc(OC)cc2-c2c1ccn2C[C@@H](C)O
null
60.9
null