original_index
int64
2
1.77M
agent_000
stringlengths
1
540
agent_001
stringlengths
1
852
agent_002
stringlengths
1
247
date_of_experiment
timestamp[ns]date
extracted_from_file
stringclasses
489 values
grant_date
timestamp[ns]date
1976-01-01 00:01:00
2016-01-01 00:09:00
is_mapped
bool
1 class
procedure_details
stringlengths
8
24.5k
product_000
stringlengths
1
484
product_001
stringlengths
1
208
reactant_000
stringlengths
1
902
reactant_001
stringlengths
1
902
reactant_002
stringlengths
1
285
rxn_str
stringlengths
87
6.12k
rxn_time
float64
0
2.16k
solvent_000
stringclasses
446 values
solvent_001
stringclasses
405 values
solvent_002
stringclasses
330 values
temperature
float64
-230
30.1k
yield_000
float64
0
90,205,156,600B
yield_001
float64
0
100M
agent_003
null
agent_004
null
agent_005
null
agent_006
null
agent_007
null
agent_008
null
agent_009
null
agent_010
null
agent_011
null
agent_012
null
agent_013
null
agent_014
null
agent_015
null
agent_016
null
solvent_003
null
solvent_004
null
solvent_005
null
solvent_006
null
solvent_007
null
solvent_008
null
solvent_009
null
solvent_010
null
101,493
O=C([O-])[O-]
[K+]
null
null
ord_dataset-d06b137b66b3478fb6a0d41a5efd32f8
1982-01-01T00:12:00
true
4-(Pentafluorophenyl)-1-carbethoxysemicarbazide, 2.13 g (0.0068 M), and potassium carbonate, 0.938 g (0.0068 M), are added to 75 ml of water. The mixture is heated at 70° C. under N2 about 12 hours. The solution is cooled in an ice bath and filtered to remove a trace of starting material. The pH of the solution is adjusted to pH 7 with concentrated HCl and extracted with ethyl acetate to remove a product which is less polar than the urazole in the TLC system, chloroform/ethyl acetate/acetic acid (5/5/1). The pH of the solution is reduced to 1 or 2 with concentrated HCl and then extracted with ethyl acetate. About 1/3 of a volume of toluene is added to the ethyl acetate and the solvents evaporated. The resulting crude solid weighs 0.569 g. The product is purified by two crystallizations from ethyl acetate/toluene (1/3 by vol). The yield of purified material is 0.476 g. It is recrystallized from H2O, mp 223°-226°.
O=c1[nH][nH]c(=O)n1-c1c(F)c(F)c(F)c(F)c1F
null
CCOC(=O)NNC(=O)Nc1c(F)c(F)c(F)c(F)c1F
null
null
[F:1][C:2]1[C:7]([NH:8][C:9](=[O:17])[NH:10][NH:11][C:12](OCC)=[O:13])=[C:6]([F:18])[C:5]([F:19])=[C:4]([F:20])[C:3]=1[F:21].C(=O)([O-])[O-].[K+].[K+]>O>[F:18][C:6]1[C:7]([N:8]2[C:9](=[O:17])[NH:10][NH:11][C:12]2=[O:13])=[C:2]([F:1])[C:3]([F:21])=[C:4]([F:20])[C:5]=1[F:19]
null
O
null
null
70
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
513,304
O=S(=O)(O)O
[NH4+]
[OH-]
null
ord_dataset-85c00026681b46f89ef8634d2b8618c3
2001-01-01T00:07:00
true
Quinoline (Formula (1), 12.9 g, 0.10 mole) was added dropwise over 5 min. with good agitation to a solution of 50 mL of concentrated sulfuric acid in a 250 mL round bottom flask. No attempt was made to control the exotherm and on this scale the final temperature was 77° C. The mixture was heated to 100° C. and 71% nitric acid (13.3 g, d. 1.42, 9.4 mL, 0.15 mole) was added at such a rate to keep the temperature between 100° C. and 110° C. Stirring was continued for an additional 30 minutes or until an HPLC (Zorbax® SB-C18 HPLC column, from Mac-Mod Analytical, Inc. of Chadds Ford, Pa. U.S.A.; dimensions 4½ mm (inside diameter) by 25 cm (length); HPLC conditions: 40:60 acetonitrile:water-0.5% ammonium acetate, 220 nm, flow 0.5 mL/min.) sample showed the reaction was complete. The mixture was cooled slightly and poured onto a mixture of 200 mL methylene chloride and 300 mL (by volume) of ice. The two phase mixture was placed in an ice bath and the temperature was kept below 25° C. while the pH was increased to 10 with concentrated ammonium hydroxide. The mixture was vacuum filtered through paper and transferred to a separatory funnel. The lower organic phase was separated and the aqueous layer was extracted with an additional 100 mL of methylene chloride. The combined organic layers were dried over magnesium sulfate, filtered and evaporated affording 15.8 g (91% yield) of a clear light amber oil which crystallized on standing. HPLC Analysis was conducted for 5-nitroquinoline and 8-nitroquinoline only: 45% 8-nitroquinoline (Formula (3), rt 9.0 min.) and 55% 5-nitroquinoline (Formula (2), rt 12.8 min).
O=[N+]([O-])c1ccc2ccccc2n1
null
O=[N+]([O-])O
c1ccc2ncccc2c1
null
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)O.[N+:16]([O-])([OH:18])=[O:17].[OH-].[NH4+]>C(Cl)Cl.O.C(#N)C>[N+:16]([C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[N:1]=1)([O-:18])=[O:17]
null
CC#N
ClCCl
O
100
null
90.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,567,738
CN(C)C(On1nnc2ccccc21)=[N+](C)C
Cl
F[P-](F)(F)(F)(F)F
null
ord_dataset-9741bb5fd93044078df2a45f45733054
2015-01-01T00:04:00
true
To a mixture of 4-isobutoxy-6-(piperazin-1-yl)pyrimidine dihydrochloride (30 mg, 0.097 mmol), (R)-2-hydroxy-2-phenylacetic acid (15 mg, 0.097 mmol), and triethylamine (0.07 mL, 0.49 mmol) in DMF was added HBTU (48 mg, 0.13 mmol), and the mixture was stirred at rt for 1 h. Then the mixture was poured onto water (3 mL), and the aqueous layer was extracted with dichloromethane (three times). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative LC-MS to give 7.2 mg (15% yields) of the title compound.
CC(C)COc1cc(N2CCN(C(=O)[C@H](O)c3ccccc3)CC2)ncn1
null
O=C(O)[C@H](O)c1ccccc1
CC(C)COc1cc(N2CCNCC2)ncn1
null
Cl.Cl.[CH2:3]([O:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[N:11]=[CH:10][N:9]=1)[CH:4]([CH3:6])[CH3:5].[OH:20][C@H:21]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:22](O)=[O:23].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:20][C@H:21]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:22]([N:17]1[CH2:18][CH2:19][N:14]([C:12]2[CH:13]=[C:8]([O:7][CH2:3][CH:4]([CH3:6])[CH3:5])[N:9]=[CH:10][N:11]=2)[CH2:15][CH2:16]1)=[O:23]
1
CN(C)C=O
CCN(CC)CC
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,413,565
null
null
null
null
ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f
2014-01-01T00:04:00
true
A solution of 2-(3-Amino-phenyl)-ethanol (2.0 g) in 48% aq HBr (20 ml) was heated at 90° C. for 18 h. The mixture was cooled to room temperature, and the precipitate formed was collected by filtration. The solid was dried in vacuo yielding Building block M, 1.8 g (61% yield). LCMS purity 90%, m/z 200/202 [M+H]+.
Nc1cccc(CCBr)c1
null
Br
Nc1cccc(CCO)c1
null
[NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9]O)[CH:5]=[CH:6][CH:7]=1.[BrH:11]>>[Br:11][CH2:9][CH2:8][C:4]1[CH:3]=[C:2]([NH2:1])[CH:7]=[CH:6][CH:5]=1
null
null
null
null
25
61
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,759,593
c1ccc([P]([Pd][P](c2ccccc2)(c2ccccc2)c2ccccc2)(c2ccccc2)c2ccccc2)cc1
O=C([O-])[O-]
[Cs+]
null
ord_dataset-97eb2ab57fec4160922caae33b54d956
2016-01-01T00:08:00
true
A 50-mL round bottomed flask fitted with a nitrogen inlet and magnetic stir bar was charged with (S)-isopropyl 7-bromo-4-(cyclopropanecarbonyl)-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate (0.801 g, 2.1 mmol), dioxane (11 mL), and water (4.6 mL). Cesium carbonate (2.053 g, 6.30 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-carboxylate (0.927 g, 3.15 mmol) were then added. The reaction was purged with nitrogen and bis(triphenylphosphine)palladium (II) dichloride (0.177 g, 0.252 mmol) was added. The mixture was heated at 90° C. with vigorous stirring for 5 h and then cooled to ambient temperature. Water (25 mL) was added, and the mixture was extracted with ethyl acetate (3×25 mL). The combined organic extracts were concentrated to afford a viscous oil and purified via column chromatography (gradient elution with 75-100% ethyl acetate-hexanes). The resulting material was triturated with diethyl ether (2×10 mL) to afford (S)-isopropyl 4-(cyclopropanecarbonyl)-3-methyl-7-(1H-pyrazol-4-yl)-3,4-dihydroquinoxaline-1(2H)-carboxylate (0.55 g, 71% yield) as a solid. MS (ESI, pos. ion) m/z 369 [M+1]+.
CC(C)OC(=O)N1C[C@H](C)N(C(=O)C2CC2)c2ccc(-c3cn[nH]c3)cc21
null
CC(C)OC(=O)N1C[C@H](C)N(C(=O)C2CC2)c2ccc(Br)cc21
CC(C)(C)OC(=O)n1cc(B2OC(C)(C)C(C)(C)O2)cn1
null
Br[C:2]1[CH:11]=[C:10]2[C:5]([N:6]([C:19]([CH:21]3[CH2:23][CH2:22]3)=[O:20])[C@@H:7]([CH3:18])[CH2:8][N:9]2[C:12]([O:14][CH:15]([CH3:17])[CH3:16])=[O:13])=[CH:4][CH:3]=1.O1CCOCC1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:44]2[CH:45]=[N:46][N:47](C(OC(C)(C)C)=O)[CH:48]=2)O1>C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH:21]1([C:19]([N:6]2[C:5]3[C:10](=[CH:11][C:2]([C:44]4[CH:45]=[N:46][NH:47][CH:48]=4)=[CH:3][CH:4]=3)[N:9]([C:12]([O:14][CH:15]([CH3:17])[CH3:16])=[O:13])[CH2:8][C@@H:7]2[CH3:18])=[O:20])[CH2:23][CH2:22]1
5
C1COCCO1
O
null
90
71.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,703,177
CCN=C=NCCCN(C)C
CN(C)c1ccncc1
Cl
null
ord_dataset-54347fcace774f89850681d6dec8009f
2016-01-01T00:03:00
true
Into a 10-mL round bottom flask, was placed a solution of 3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzoic acid (118.8 mg, 0.45 mmol, 1.50 equiv) in dichloromethane (24 mL), EDC.HCl (171.6 mg, 0.90 mmol, 3.00 equiv), 4-dimethylaminopyridine (182.4 mg, 1.49 mmol, 5.00 equiv), and 2-amino-N-(5-(3,4-dimethylphenyl)pyrimidin-2-yl)-5-(piperidin-1-yl)benzamide (120 mg, 0.29 mmol, 1.00 equiv). The resulting solution was stirred for 8 h at 25° C. in an oil bath. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 139.2 mg (62%) of a yellow solid. 1H-NMR (300 MHz, DMSO, ppm): δ 11.37 (s, 1H), 11.30 (s, 1H), 8.75 (d, J=6 Hz, 2H), 8.22 (d, J=9 Hz, 1H), 8.054 (s, 1H), 7.93 (d, J=6.3 Hz, 1H), 7.68˜7.60 (m, 2H), 7.53 (s, 1H), 7.31˜7.20 (m, 3H), 7.15 (d, J=7.2 Hz, 1H), 3.40˜3.12 (m, 13H), 2.59 (s, 2H), 2.32˜2.27 (m, 4H), 2.16 (s, 3H), 1.68 (m, 4H), 1.58˜1.57 (m, 2H), 1.21˜1.16 (m, 6H). MS (ES, m/z): 648 [M−H]+.
CCN(CC)CCN(C)Cc1cccc(C(=O)Nc2ccc(N3CCCCC3)cc2C(=O)Nc2ncc(-c3ccc(C)c(C)c3)cn2)c1
null
Cc1ccc(-c2cnc(NC(=O)c3cc(N4CCCCC4)ccc3N)nc2)cc1C
CCN(CC)CCN(C)Cc1cccc(C(=O)O)c1
null
[CH2:1]([N:3]([CH2:18][CH3:19])[CH2:4][CH2:5][N:6]([CH2:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([OH:14])=O)[CH3:7])[CH3:2].CCN=C=NCCCN(C)C.Cl.[NH2:32][C:33]1[CH:55]=[CH:54][C:53]([N:56]2[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]2)=[CH:52][C:34]=1[C:35]([NH:37][C:38]1[N:43]=[CH:42][C:41]([C:44]2[CH:49]=[CH:48][C:47]([CH3:50])=[C:46]([CH3:51])[CH:45]=2)=[CH:40][N:39]=1)=[O:36]>ClCCl.CN(C)C1C=CN=CC=1>[CH2:18]([N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][N:6]([CH2:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([NH:32][C:33]1[CH:55]=[CH:54][C:53]([N:56]2[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]2)=[CH:52][C:34]=1[C:35]([NH:37][C:38]1[N:43]=[CH:42][C:41]([C:44]2[CH:49]=[CH:48][C:47]([CH3:50])=[C:46]([CH3:51])[CH:45]=2)=[CH:40][N:39]=1)=[O:36])=[O:14])[CH3:7])[CH3:19]
8
ClCCl
null
null
25
74.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
607,296
[Na+]
[OH-]
null
null
ord_dataset-273fda773e864aaf9b71a30a2d9f2162
2003-01-01T00:08:00
true
To a well-stirred reaction vessel equipped with a thermometer and a pH electrode were added 39 g of water and 0.20 g of Arquad CB50 at 5° C. After the addition of 0.05 mole of 3-chlorobenzoic acid the pH was adjusted to 6 using a 10 wt % aqueous NaOH solution. Then, 0.05 mole of sec-butyl chloroformate was dosed within 5 min at 5° C. During this time and a post-reaction time of 165 min at 5° C. the pH was kept at a value between 6 and 9. The reaction mixture was allowed to separate, giving 12.5 g of 3-chlorobenzoyl 1-methyl-1-propyl carbonate having a content of 98% in a yield of 95%.
CCC(C)OC(=O)OC(=O)c1cccc(Cl)c1
null
O=C(O)c1cccc(Cl)c1
CCC(C)OC(=O)Cl
null
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[OH-].[Na+].Cl[C:14]([O:16][CH:17]([CH2:19][CH3:20])[CH3:18])=[O:15]>O>[C:14](=[O:15])([O:16][CH:17]([CH3:18])[CH2:19][CH3:20])[O:6][C:5](=[O:7])[C:4]1[CH:8]=[CH:9][CH:10]=[C:2]([Cl:1])[CH:3]=1
null
O
null
null
null
97.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,648,404
[Na+]
[OH-]
null
null
ord_dataset-bcc0b01d4f58457a8733b10a099f43ba
2015-01-01T00:10:00
true
To a solution of 1-(dodecylamino)-4-(methylsulfinyl)-1-oxobutan-2-yl acetate (25 g, 62.6 mmol) in methanol (350 mL) was added 2.5 N NaOH (40 mL, 100 mmol) and the resulting solution was stirred at room temperature for 5 hrs. The reaction was quenched with concentrated HCL (12.5 mL) and then evaporated to a small volume. The resulting mixture was treated with EtOAc (200 mL) and then washed with 1N HCl (150 mL), saturated sodium bicarbonate (50 mL), dried over magnesium sulfate, filtered and evaporated to give a solid. The solid was dissolved in dichloromethane and purified by silica gel chromatography with 0-10% methanol/dichloromethane. The desired fractions were collected and evaporated to give a white solid (16.7 g, 80%). 1H NMR (500 MHz, DMSO-d6) δ ppm 0.85 (t, J=6.83 Hz, 3 H) 1.15-1.33 (m, 18 H) 1.33-1.46 (m, 2 H) 1.72-1.87 (m, 1 H) 1.92-2.09 (m, 1 H) 2.51 (d, J=1.27 Hz, 3 H) 2.56-2.87 (m, 2 H) 3.00-3.12 (m, 2 H) 3.90-4.00 (m, 1 H) 5.69 (d, J=5.40 Hz, 1 H) 7.71-7.82 (m, 1 H). m/z 334 (MH+).
CCCCCCCCCCCCNC(=O)C(O)CCS(C)=O
null
CCCCCCCCCCCCNC(=O)C(CCS(C)=O)OC(C)=O
null
null
C([O:4][CH:5]([CH2:21][CH2:22][S:23]([CH3:25])=[O:24])[C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])=[O:7])(=O)C.[OH-].[Na+]>CO.ClCCl>[CH2:9]([NH:8][C:6](=[O:7])[CH:5]([OH:4])[CH2:21][CH2:22][S:23]([CH3:25])=[O:24])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
5
CO
ClCCl
null
25
null
80
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,541,277
null
null
null
null
ord_dataset-cac8df8aff894288876df4e093c9877f
2015-01-01T00:02:00
true
A mixture of 1-benzyl-1,2,3,4-tetrahydroquinolin-7-ol (500 mg, 2.09 mM) and triethylamine in dry tetrahydrofuran (THF, 5 ml) was stirred for half an hour under nitrogen atmosphere at room temperature (35° C.). To the stirred reaction mixture, 2-methoxyphenyl isocyanate (417 mg/ml, 3.14 mM) was added at once and then the reaction mixture was further stirred for 72 hours under N2 atmosphere at RT. The reaction mixture was concentrated under vacuum and then was added distilled water (15 mL) followed by the extraction with ether (3×15 mL). The ether layer was dried over sodium sulphate and concentrated under vacuum to afford the crude product, which was finally chromatographed using chloroform-hexane (1:9) to give 8i as solid. Yield: 0.623 g, 76.85%.
COc1ccccc1NC(=O)Oc1ccc2c(c1)N(Cc1ccccc1)CCC2
null
COc1ccccc1N=C=O
Oc1ccc2c(c1)N(Cc1ccccc1)CCC2
null
[CH2:1]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([OH:18])[CH:16]=2)[CH2:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[N:34]=[C:35]=[O:36]>O1CCCC1>[CH3:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[NH:34][C:35](=[O:36])[O:18][C:15]1[CH:16]=[C:17]2[C:12]([CH2:11][CH2:10][CH2:9][N:8]2[CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:13][CH:14]=1
null
CCN(CC)CC
C1CCOC1
null
35
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
427,386
null
null
null
null
ord_dataset-8cce6f317d644b348a7978a2dce3ea01
1999-01-01T00:03:00
true
Following a procedure and using relative proportions of starting materials similar to those described in Example 4, but using tert-butyl (4-methyl-1-methylthiocarbazol-2-yl)acetate and 4-fluorobenzyl bromide as starting materials, the title compound was obtained in a yield of 91% as an oil.
CSc1c(CC(=O)OC(C)(C)C)cc(C)c2c3ccccc3n(Cc3ccc(F)cc3)c12
null
CSc1c(CC(=O)OC(C)(C)C)cc(C)c2c1[nH]c1ccccc12
Fc1ccc(CBr)cc1
null
[CH3:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:5]([S:15][CH3:16])=[C:4]([CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:3]=1.[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Br)=[CH:28][CH:27]=1>>[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][N:7]2[C:6]3[C:5]([S:15][CH3:16])=[C:4]([CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:3]=[C:2]([CH3:1])[C:14]=3[C:13]3[C:8]2=[CH:9][CH:10]=[CH:11][CH:12]=3)=[CH:28][CH:27]=1
null
null
null
null
null
91
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,717,329
[Na+]
[OH-]
null
null
ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb
2016-01-01T00:04:00
true
[5-(4-Bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid (R)-1-phenyl-ethyl ester (from Example 1, 566 mg, 1.41 mmol), methyl 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropanecarboxylate (511 mg, 1.69 mmol), X-Phos (134 mg, 0.28 mmol), palladium acetate (31.7 mg, 0.14 mmol) and potassium phosphate (898 mg, 4.23 mmol) were combined in toluene (12 mL) and degassed water (3 mL) was added. The mixture was degassed and sealed. The mixture was stirred at 95° C. for 3 hrs and cooled to room temperature. The mixture was extracted with ethyl acetate and water. The organic layer was washed with brine and dried. Solvents were evaporated and the residue was purified by flash column chromatography (40 g silica gel, ethyl acetate in hexanes 10% to 70% in 15 minutes) to give 1-{4′-[1-methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazol-4-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid methyl ester as a pale yellow solid (370 mg, 52.8% yield). LC/MS calcd for C29H28N4O4 (m/e) 496.0, obsd 497.0 (M+H); 1H-NMR (400 MHz, CDCl3) δ ppm 1.25 (m, 3H), 1.66 (m, 4H), 3.67 (s, 3H), 3.93 (s, 3H), 5.91 (m, 1H), 6.44 (br, 1H), 7.29-7.40 (m, 5H), 7.44 (d, J=8.1 Hz, 2H), 7.57 (d, J=8.3 Hz, 2H), 7.61 (d, J=8.3 Hz, 2H), 7.78 (br d, J=6.6 Hz, 2H). 1-{4′-[1-Methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazol-4-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid methyl ester (50 mg) was dissolved in 1 mL of THF and 1 mL of ethanol. To this mixture was added 1N sodium hydroxide solution (1 mL). The clear solution was stirred at room temperature for 12 hrs. Solvents were evaporated and the residue was treated with 2N hydrochloric acid (1.4 mL). The solid was filtered and rinsed with water, dried in the air, to give 1-{4′-[1-methyl-5-((R)-1-phenyl-ethoxycarbonylamino)-1H-[1,2,3]triazol-4-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid (47.5 mg, 97.8% yield). LC/MS calcd for C28H26N4O4 (m/e) 482.0, obsd 483.0 (M+H); 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.14-1.24 (m, 3H), 1.49 (m, 2H), 1.59 (m, 2H), 3.86 (s, 3H), 5.80 (m, 1H), 7.28-7.50 (m, 7H), 7.63 (d, J=8.1 Hz, 2H), 7.71 (m, 2H), 7.80 (d, J=7.6 Hz, 2H), 9.95 and 9.62 (br s, 1H), 12.35 (s, 1H).
C[C@@H](OC(=O)Nc1c(-c2ccc(-c3ccc(C4(C(=O)O)CC4)cc3)cc2)nnn1C)c1ccccc1
null
COC(=O)C1(c2ccc(-c3ccc(-c4nnn(C)c4NC(=O)O[C@H](C)c4ccccc4)cc3)cc2)CC1
null
null
C[O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]4[N:21]=[N:22][N:23]([CH3:37])[C:24]=4[NH:25][C:26]([O:28][C@@H:29]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[CH3:30])=[O:27])=[CH:16][CH:15]=3)=[CH:10][CH:9]=2)[CH2:7][CH2:6]1)=[O:4].[OH-].[Na+]>C1COCC1.C(O)C>[CH3:37][N:23]1[C:24]([NH:25][C:26]([O:28][C@@H:29]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH3:30])=[O:27])=[C:20]([C:17]2[CH:18]=[CH:19][C:14]([C:11]3[CH:10]=[CH:9][C:8]([C:5]4([C:3]([OH:4])=[O:2])[CH2:7][CH2:6]4)=[CH:13][CH:12]=3)=[CH:15][CH:16]=2)[N:21]=[N:22]1
12
C1CCOC1
CCO
null
25
null
97.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,171,928
[K+]
[OH-]
null
null
ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880
2012-01-01T00:05:00
true
Potassium hydroxide (108 mg, 1.93 mmol) was added in one portion to (S)-methyl 2-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)-3-methylbutanoate (Intermediate 17-1; 327.4 mg, 0.64 mmol) in t-BuOH (4150 μL) at RT. The resulting solution was stirred at 45° C. for 5 hours a precipitate formed. The reaction mixture was quenched with 2M HCl (5 mL), The reaction mixture was evaporated to dryness and redissolved in water (10 mL), and filtered through nylon, washed with water and dried under vacuum. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford (S)-2-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)-3-methylbutanoic acid (93 mg, 29.1%) as a white solid.
Cc1nc(C)c(-c2ccc(-c3ccc(CC(=O)N[C@H](C(=O)O)C(C)C)cc3Cl)cc2)nc1C(N)=O
null
COC(=O)[C@@H](NC(=O)Cc1ccc(-c2ccc(-c3nc(C(N)=O)c(C)nc3C)cc2)c(Cl)c1)C(C)C
null
null
[OH-].[K+].[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C:25]([NH:27][C@@H:28]([CH:33]([CH3:35])[CH3:34])[C:29]([O:31]C)=[O:30])=[O:26])=[CH:20][C:19]=3[Cl:36])=[CH:14][CH:13]=2)[C:9]([CH3:37])=[N:8][C:7]=1[CH3:38])(=[O:5])[NH2:4]>CC(O)(C)C>[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C:25]([NH:27][C@@H:28]([CH:33]([CH3:34])[CH3:35])[C:29]([OH:31])=[O:30])=[O:26])=[CH:20][C:19]=3[Cl:36])=[CH:14][CH:13]=2)[C:9]([CH3:37])=[N:8][C:7]=1[CH3:38])(=[O:5])[NH2:4]
5
CC(C)(C)O
null
null
45
null
29.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,472,442
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
O=C([O-])[O-]
[K+]
null
ord_dataset-fd1fa959d6264608b0b7fcda16741bfd
2014-01-01T00:08:00
true
A mixture of the compound obtained from step f above (1.0 g) (4-chlorophenyl)boronic acid (0.76 g), tetrakis(triphenylphosphine)palladium (0) (0.14 g), and potassium carbonate (1.0 g) in dry dimethylformamide (10 mL) was heated at 110° C. for 4 hours. Ethyl acetate and water were added to the reaction mixture. The organic layer was separated, washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a residue which was purified by column chromatography over silica gel using 12% ethyl acetate in hexane as eluant to afford the title compound (0.9 g).
CCOC(=O)C[C@H]1[C@H]2OC(C)(C)O[C@H]2O[C@@H]1/C=C/c1ccc(-c2ccc(Cl)cc2)cc1
null
OB(O)c1ccc(Cl)cc1
CCOC(=O)C[C@H]1[C@H]2OC(C)(C)O[C@H]2O[C@@H]1/C=C/c1ccc(Br)cc1
null
Br[C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C@H:10]2[O:19][C@@H:13]3[O:14][C:15]([CH3:18])([CH3:17])[O:16][C@@H:12]3[C@@H:11]2[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:4][CH:3]=1.[Cl:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([C:2]2[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C@H:10]3[O:19][C@@H:13]4[O:14][C:15]([CH3:18])([CH3:17])[O:16][C@@H:12]4[C@@H:11]3[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:4][CH:3]=2)=[CH:29][CH:28]=1
null
O
CCOC(C)=O
CN(C)C=O
110
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
773,500
Cl
null
null
null
ord_dataset-8214eb8444a44dc2900ccb42dbeff15e
2007-01-01T00:05:00
true
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl chloride (0.250 g, 0.808 mmol) was added to a solution of 3-methylsulfonylaniline hydrochloride (0.184 g, 0.889 mmol) and triethylamine (0.563 mL, 4.04 mmol) in acetonitrile (20 mL). The reaction mixture heated at 60° C. for 12 h, concentrated and crude product purified by column chromatography on silica gel to give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid (3-methane sulfonyl-phenyl)-amide. 1H-NMR (CD3OD, 300 MHz) δ 8.37 (s, 1H), 8.17 (s, 1H), 7.97 (d, 1H, J=8.5 Hz), 7.73 (d, 1H, J=8.0 Hz), 7.59–7.66 (m, 3H), 7.51 (d, 2H, J=8.8 Hz), 3.15 (s, 3H); LCMS m/z=443.9 (M+H)+.
CS(=O)(=O)c1cccc(NC(=O)c2cnn(-c3ccc(Cl)cc3)c2C(F)(F)F)c1
null
CS(=O)(=O)c1cccc(N)c1
O=C(Cl)c1cnn(-c2ccc(Cl)cc2)c1C(F)(F)F
null
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]([F:16])([F:15])[F:14])=[C:11]([C:17](Cl)=[O:18])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.Cl.[CH3:21][S:22]([C:25]1[CH:26]=[C:27]([CH:29]=[CH:30][CH:31]=1)[NH2:28])(=[O:24])=[O:23].C(N(CC)CC)C>C(#N)C>[CH3:21][S:22]([C:25]1[CH:26]=[C:27]([NH:28][C:17]([C:11]2[CH:10]=[N:9][N:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[C:12]=2[C:13]([F:16])([F:15])[F:14])=[O:18])[CH:29]=[CH:30][CH:31]=1)(=[O:23])=[O:24]
null
CC#N
CCN(CC)CC
null
60
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,142,141
null
null
null
null
ord_dataset-68715347640045adb1b09e6a04722b0e
2012-01-01T00:03:00
true
Method A using 3-Iodo-pyridine-2,6-diamine (Preparation 44), 1.6 equivalents of lutidine and 1.5 equivalents of acid chloride prepared from 2-isopropyl-2H-pyrazole-3-carboxylic acid. Purified by trituration with methanol:ethylacetate 1:2 to afford the title compound as a colourless oil (608 mg, 38%).
CC(C)n1nccc1C(=O)Nc1ccc(I)c(N)n1
null
CC(C)n1nccc1C(=O)O
Nc1ccc(I)c(N)n1
null
[I:1][C:2]1[C:3]([NH2:9])=[N:4][C:5]([NH2:8])=[CH:6][CH:7]=1.N1C(C)=CC=CC=1C.[CH:18]([N:21]1[C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=[N:22]1)([CH3:20])[CH3:19]>>[NH2:9][C:3]1[N:4]=[C:5]([NH:8][C:26]([C:25]2[N:21]([CH:18]([CH3:20])[CH3:19])[N:22]=[CH:23][CH:24]=2)=[O:27])[CH:6]=[CH:7][C:2]=1[I:1]
null
Cc1cccc(C)n1
null
null
null
null
38
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,061,171
O=C([O-])[O-]
[K+]
null
null
ord_dataset-ffbef48837674f39816de887b5dc8bae
2011-01-01T00:06:00
true
Potassium carbonate (4.42 g, 31.96 mmol) was suspended in dry MeOH (20 mL) and thioacetic acid (2.28 g, 29.96 mmol) was added. The mixture was stirred vigorously for 10 mins, concentrated and diluted in dry DMF (30 mL). tert-Butyl 3-[(methylsulfonyl)oxy]pyrrolidine-1-carboxylate (2.65 g, 9.99 mmol) dissolved in dry DMF (20 mL) was added and the reaction mixture was heated to 60° C. for 3.5 h. The reaction mixture was diluted with water (350 mL) and extracted with EtOAc (2×150 mL) The organic phases were dried with MgSO4, filtered and evaporated. The crude product was purified using Biotage Horizon HPFC system (25+M column, isocratic run heptane/EtOAc (60:40)) affording the title compound (0.592 g, 24.2%) (the product is a mixture of cis and trans isomers). 1H NMR (500 MHz, CDCl3): δ 1.41 (d, 18H), 1.66 (d, 1H), 1.74-1.86 (m, 2H), 2.20-2.26 (m, 2H), 2.29 (s, 3H), 3.10-3.26 (m, 2H), 3.30-3.43 (m, 4H), 3.46-3.54 (m, 1H), 3.66-3.74 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 28.68, 30.82, 31.25, 32.34, 36.16, 41.09, 44.88, 51.60, 55.37, 79.67, 154.43; Mass Spectrum: M+H+ 241.
CC(=O)SC1CCN(C(=O)OC(C)(C)C)C1
null
CC(O)=S
CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)C1
null
C(=O)([O-])[O-].[K+].[K+].[C:7]([OH:10])(=[S:9])[CH3:8].CS(O[CH:16]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17]1)(=O)=O>CO.CN(C=O)C.O>[C:7]([S:9][CH:20]1[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19]1)(=[O:10])[CH3:8]
0.17
O
CO
CN(C)C=O
60
null
24.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
206,585
O=C([O-])O
O=S(=O)(O)O
[Na+]
null
ord_dataset-dd1de64954674e17b4b690cac09dc67b
1990-01-01T00:04:00
true
A solution of (S)-2-(4-chlorophenyl)-α-methyl-3H-imidazo[4,5-b]pyridine-3-acetic acid (3.0 g, 0.00995 mole) and concentrated sulfuric acid (4 drops) in ethylene glycol (50 ml) was refluxed under nitrogen for three hours, and then poured into a saturated sodium bicarbonate solution (200 ml). Water (50 ml) was added and the product was extracted into two portions of ethyl acetate. The combined organic layers were washed twice with water and once with a saturated sodium chloride solution, dried over magnesium sulfate, treated with charcoal and filtered. Evaporation of the solvents under reduced pressure gave 1.9 g (56% yield) of solid which was dissolved in hot isopropyl ether (with a little isopropyl alcohol added). The solution was stirred and cooled to room temperature to precipitate a solid. The mixture was cooled in the freezer, the solid was collected by filtration, rinsed with isopropyl ether and dried under high vacuum at room temperature overnight to give 1.44 g of title compound, mp 112°-113.5° C.
C[C@@H](C(=O)OCCO)n1c(-c2ccc(Cl)cc2)nc2cccnc21
null
C[C@@H](C(=O)O)n1c(-c2ccc(Cl)cc2)nc2cccnc21
OCCO
null
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:16]([C@@H:17]([CH3:21])[C:18]([OH:20])=[O:19])[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].O.[CH2:28](O)[CH2:29][OH:30]>S(=O)(=O)(O)O>[OH:30][CH2:29][CH2:28][O:19][C:18](=[O:20])[C@H:17]([CH3:21])[N:16]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[N:9]=[C:8]1[C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1
null
O
null
null
null
null
56
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,232,545
Cc1cc(NC(=O)c2ccc(Cl)nc2)ccc1I
null
null
null
ord_dataset-e96f5a2842f14e5380461c234100f05a
2012-01-01T00:12:00
true
N-(4-tert-Butyl-pyrimidin-2-yl)-6-chloro-nicotinamide was prepared from 4-tert-butyl-pyrimidin-2-ylamine (prepared as described in J. Org. Chem. 1977, 221) and 6-chloronicotinoyl chloride following a procedure similar to the one described in the synthesis of 6-chloro-N-(4-iodo-3-methyl-phenyl)-nicotinamide, above. The product was isolated after silica gel purification with 20-40% EtOAc in hexanes gradient followed by suspension in hexanes and filtration. HRMS m/z calcd for C14H15N4OCl [M+H]+: 291.1007. Found: 291.1007.
CC(C)(C)c1ccnc(NC(=O)c2ccc(Cl)nc2)n1
null
O=C(Cl)c1ccc(Cl)nc1
CC(C)(C)c1ccnc(N)n1
null
[C:1]([C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](Cl)=[O:18])=[CH:15][N:14]=1.ClC1C=CC(C(NC2C=CC(I)=C(C)C=2)=O)=CN=1>>[C:1]([C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:17](=[O:18])[C:16]2[CH:20]=[CH:21][C:13]([Cl:12])=[N:14][CH:15]=2)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,075,554
null
null
null
null
ord_dataset-afd812677c134591a99f46ce28de2524
2011-01-01T00:08:00
true
In analogy to the procedure described for the preparation of the Building Block AU, the reaction of the 3-bromo-N-methoxy-N-methyl-5-(2,2,2-trifluoro-ethoxy)-benzamide and 4-bromo-1-methoxy-2-methyl-benzene, beforehand transformed to the Grignard reagent, yielded the title compound as a white solid (yield: 75% of theory). Mass (calculated) C17H14BrF3O3 [402]; (found) [M]+=403, 405.
COc1ccc(C(=O)c2cc(Br)cc(OCC(F)(F)F)c2)cc1C
null
CON(C)C(=O)c1cc(Br)cc(OCC(F)(F)F)c1
COc1ccc(Br)cc1C
null
[Br:1][C:2]1[CH:3]=[C:4]([CH:11]=[C:12]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[CH:13]=1)[C:5](N(OC)C)=[O:6].Br[C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([CH3:29])[CH:22]=1>>[Br:1][C:2]1[CH:3]=[C:4]([C:5]([C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([CH3:29])[CH:22]=2)=[O:6])[CH:11]=[C:12]([O:14][CH2:15][C:16]([F:17])([F:18])[F:19])[CH:13]=1
null
null
null
null
null
75
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,681,720
O=[Ru](=O)(=O)[O-]
CCC[N+](CCC)(CCC)CCC
C[N+]1([O-])CCOCC1
null
ord_dataset-3953983e052a4076aa7cc0880b79cb8b
2016-01-01T00:01:00
true
To a solution of N-(1-(4-(hydroxymethyl)phenyl)piperidin-4-yl)benzamide (1.1 g, 3.5 mmol) in CH2Cl2 (250 mL) was added TPAP (0.123 g, 0.35 mmol) and NMO (0.623 g, 5.3 mmol). After 1 hour, the mixture was filtered through Celite, concentrated, and purified by silica gel chromatography, eluting with 30% ethyl acetate/hexanes to 100% ethyl acetate, to afford N-(1-(4-formylphenyl)piperidin-4-yl)benzamide as a white solid (0.350 g, 32%).
O=Cc1ccc(N2CCC(NC(=O)c3ccccc3)CC2)cc1
null
O=C(NC1CCN(c2ccc(CO)cc2)CC1)c1ccccc1
null
null
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([NH:15][C:16](=[O:23])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.C[N+]1([O-])CCOCC1>C(Cl)Cl.CCC[N+](CCC)(CCC)CCC.[O-][Ru](=O)(=O)=O>[CH:2]([C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:10][CH2:11][CH:12]([NH:15][C:16](=[O:23])[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:13][CH2:14]2)=[CH:7][CH:8]=1)=[O:1]
1
ClCCl
null
null
null
32.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
880,371
Cl
[Li+]
[OH-]
null
ord_dataset-3592bd645cd143ee8274cd0d834ae581
2009-01-01T00:05:00
true
0.57 g (13.6 mmol) of lithium hydroxide monohydrate and 70 cm3 of water are added at a temperature in the region of 20° C. to 1.45 g (4.53 mmol) of 6-fluoro-3-methoxycarbonyl-1-(quinol-4-yl)-1H-indole dissolved in 70 cm3 of tetrahydrofuran. After stirring at the reflux point of the solvent for 16 hours, the reaction mixture is concentrated under reduced pressure (2.7 kPa) to give a residue which is taken up with 13.6 cm3 of N hydrochloric acid. After filtering off and drying the solid residue at atmospheric pressure at 60° C., 1.35 g of 3-carboxy-6-fluoro-1-(quinol-4-yl)-1H-indole are obtained in the form of a yellow solid melting at 190° C.
O=C(O)c1cn(-c2ccnc3ccccc23)c2cc(F)ccc12
null
COC(=O)c1cn(-c2ccnc3ccccc23)c2cc(F)ccc12
null
null
O.[OH-].[Li+].O.[F:5][C:6]1[CH:14]=[C:13]2[C:9]([C:10]([C:25]([O:27]C)=[O:26])=[CH:11][N:12]2[C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=[CH:17][CH:16]=2)=[CH:8][CH:7]=1.Cl>O1CCCC1>[C:25]([C:10]1[C:9]2[C:13](=[CH:14][C:6]([F:5])=[CH:7][CH:8]=2)[N:12]([C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=[CH:17][CH:16]=2)[CH:11]=1)([OH:27])=[O:26]
16
C1CCOC1
O
null
null
97.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,406,053
O=C([O-])[O-]
[K+]
null
null
ord_dataset-7456bda2326f4bebaa874a5474d4cc0d
2014-01-01T00:03:00
true
528 mg of 2,6-dichloroisonicotinaldehyde (this compound was prepared by the method described in J. Chem. Soc., Chem. Commun., 1998, 1567-1568) was dissolved in 10 ml of methanol, and 586 mg of p-toluenesulfonyl methyl isocyanide and 415 mg of potassium carbonate ware added, and the mixture was stirred at 50° C. for 30 minutes. The reaction solution was concentrated, and then diluted with ethyl acetate, and the organic layer was washed with a saturated aqueous solution of sodium bicarbonate and brine, and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 630 mg of the objective compound as white powder.
Clc1cc(-c2cnco2)cc(Cl)n1
null
O=Cc1cc(Cl)nc(Cl)c1
[C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
null
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:10])[N:9]=1)[CH:5]=[O:6].C1(C)C=CC(S([CH2:20][N+:21]#[C-:22])(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:6][CH:22]=[N:21][CH:20]=2)[CH:7]=[C:8]([Cl:10])[N:9]=1
0.5
CO
null
null
50
97.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,456,533
[Na+]
[OH-]
null
null
ord_dataset-a86112d52cd54525a5e36d41f18aced2
2014-01-01T00:07:00
true
To a solution of ethyl 6-chloro-7-(4-(6-(2-chloro-4-(trifluoromethyl)phenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylate (0.034 g, 0.054 mmol) in 3:1 THF/EtOH (1 ml) was added 1M sodium hydroxide (0.22 ml, 0.22 mmol), and the reaction was stirred at ambient temperature for 16 hours. The reaction was concentrated to dryness, taken up in water, and acidified with 1M hydrochloric acid. The reaction was extracted twice with EtOAc, and the combined organic layers were washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated to yield the desired compound (0.030 g, 0.050 mmol, 92% yield).
O=C(Nc1ccc(-c2ccc(C(F)(F)F)cc2Cl)nn1)c1ccc(Oc2cc3c(cc2Cl)C(C(=O)O)CCO3)cc1
null
CCOC(=O)C1CCOc2cc(Oc3ccc(C(=O)Nc4ccc(-c5ccc(C(F)(F)F)cc5Cl)nn4)cc3)c(Cl)cc21
null
null
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:38])[NH:20][C:21]3[N:22]=[N:23][C:24]([C:27]4[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][C:28]=4[Cl:37])=[CH:25][CH:26]=3)=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:39]([O:41]CC)=[O:40].[OH-].[Na+]>C1COCC1.CCO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:38])[NH:20][C:21]3[N:22]=[N:23][C:24]([C:27]4[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:34])[F:35])=[CH:29][C:28]=4[Cl:37])=[CH:25][CH:26]=3)=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:39]([OH:41])=[O:40]
16
CCO
C1CCOC1
null
25
92.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
992,735
[Na+]
[OH-]
null
null
ord_dataset-b6d8835b0c934476a36e6149e7597487
2010-01-01T00:09:00
true
Water (1 mL) was added in one portion to a stirred solution of benzyl [2-chloro-4-(1,4-dioxaspiro[4.5]dec-8-yl)phenyl]carbamate (2.60 g, 6.47 mmol) in TFA (20 mL) and the reaction mixture was stirred at room temperature for 2 h. The mixture was cooled to 10° C. and a 2N aqueous solution of sodium hydroxide was added until the pH of the mixture was 10. Ethyl acetate (50 mL) was added and the layers were separated and the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were washed with H2O and brine, dried (MgSO4) and concentrated in vacuo to leave the title compound (2.3 g, 99%) as a solid; 1H NMR δ 1.82-1.99 (2H, m), 2.17-2.28 (2H, m), 2.45-2.57 (4H, m), 2.94-3.07 (1H, m), 5.24 (2H, s), 7.17 (1H, dd), 7.25 (1H, d), 7.32-7.5 (5H, m), 8.13 (1H, d); MS m/e (M−H)− 356.
O=C1CCC(c2ccc(NC(=O)OCc3ccccc3)c(Cl)c2)CC1
null
O=C(Nc1ccc(C2CCC3(CC2)OCCO3)cc1Cl)OCc1ccccc1
null
null
O.[Cl:2][C:3]1[CH:8]=[C:7]([CH:9]2[CH2:18][CH2:17][C:12]3(OCC[O:13]3)[CH2:11][CH2:10]2)[CH:6]=[CH:5][C:4]=1[NH:19][C:20](=[O:29])[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[OH-].[Na+].C(OCC)(=O)C>C(O)(C(F)(F)F)=O>[Cl:2][C:3]1[CH:8]=[C:7]([CH:9]2[CH2:18][CH2:17][C:12](=[O:13])[CH2:11][CH2:10]2)[CH:6]=[CH:5][C:4]=1[NH:19][C:20](=[O:29])[O:21][CH2:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
2
CCOC(C)=O
O=C(O)C(F)(F)F
O
25
99.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,514,297
OBO
null
null
null
ord_dataset-8c74302143c04eb9983e4b3a7ead2d72
2014-01-01T00:12:00
true
2-(thiophen-3-yl)nicotinaldehyde was prepared using the general boronic acid coupling procedure for 2-bromonicotinaldehyde and thiophen-3-ylboronic acid (60 mg, 101.8 mg theoretical, 58.9%). LC-MS m/z 190.2 (M+1).
O=Cc1cccnc1-c1ccsc1
null
O=Cc1cccnc1Br
OB(O)c1ccsc1
null
B(O)O.Br[C:5]1[N:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH:7]=[O:8].[S:13]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14]1>>[S:13]1[CH:17]=[CH:16][C:15]([C:5]2[N:12]=[CH:11][CH:10]=[CH:9][C:6]=2[CH:7]=[O:8])=[CH:14]1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
422,604
O=C([O-])[O-]
[K+]
null
null
ord_dataset-1a231de00bfe4443b547e1f03885ed41
1999-01-01T00:01:00
true
A solution of 2-hydroxydibenzofuran (2.0 grams) was treated with allyl bromide (1.2 mL) and potassium carbonate (1.5 grams). The mixture was stirred over night at 60°. The reaction was partitioned between methylene chloride and water. The organic was washed once with water and dried over sodium sulfate. The organic layer was filtered and concentrated to an oil which was chromatographed over silica gel to afford the title compound.
CC=COc1ccc2oc3ccccc3c2c1
null
Oc1ccc2oc3ccccc3c2c1
C=CCBr
null
[OH:1][C:2]1[CH:14]=[CH:13][C:5]2[O:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[CH2:15](Br)[CH:16]=[CH2:17].C(=O)([O-])[O-].[K+].[K+]>>[CH:15]([O:1][C:2]1[CH:14]=[CH:13][C:5]2[O:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[C:4]=2[CH:3]=1)=[CH:16][CH3:17]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,045,551
[Li+]
[OH-]
null
null
ord_dataset-dd320ded4b3f4764af39de99491533f7
2011-01-01T00:04:00
true
To ethyl 2-oxo-2,3-dihydrobenzo[d]oxazole-6-carboxylate in THF (20 mL) was added LiOH (2 g in 10 mL water). The mixture was stirred at room temperature for 20 hours. The solvent was evaporated. The residue was taken up in water and acidified with 5 N HCl to pH=5. The solid was recovered by filtration, washing with water, to provide the pure product as a tan solid (1.44 g, 80%). LCMS (API-ES) m/z: 180 (M+H+).
O=C(O)c1ccc2[nH]c(=O)oc2c1
null
CCOC(=O)c1ccc2[nH]c(=O)oc2c1
null
null
[O:1]=[C:2]1[NH:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]([O:13]CC)=[O:12])=[CH:10][C:4]=2[O:3]1.[Li+].[OH-]>C1COCC1>[O:1]=[C:2]1[NH:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]([OH:13])=[O:12])=[CH:10][C:4]=2[O:3]1
20
C1CCOC1
null
null
25
null
80
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
753,184
null
null
null
null
ord_dataset-844a22e1fcab44a5b59c5e2922b2855a
2007-01-01T00:01:00
true
Utilising the procedure described in example 1b but employing 3-[(aminoiminomethyl)amino]-benzoic acid ethyl ester mononitrate in lieu of 3-[(aminoiminomethyl)amino]-4-methyl-benzoic acid ethyl ester mononitrate, afforded the title compound as a crystalline solid, m.p. 197–199° C.
CCOC(=O)c1cccc(Nc2nccc(-c3cccnc3)n2)c1
null
O=[N+]([O-])O
CCOC(=O)c1ccc(C)c(NC=NN)c1
CCOC(=O)c1cccc(NC=NN)c1
[N+]([O-])(O)=O.[CH2:5]([O:7][C:8](=[O:19])[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH:16]=[N:17]N)[CH:10]=1)[CH3:6].[N+:20]([O-])(O)=O.C(OC(=O)[C:28]1[CH:33]=[CH:32][C:31]([CH3:34])=[C:30]([NH:35][CH:36]=NN)[CH:29]=1)C>>[CH2:5]([O:7][C:8](=[O:19])[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][C:16]2[N:20]=[C:32]([C:33]3[CH:36]=[N:35][CH:30]=[CH:29][CH:28]=3)[CH:31]=[CH:34][N:17]=2)[CH:10]=1)[CH3:6]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,589,517
null
null
null
null
ord_dataset-e8c6a25568b64529b960953990e6921f
2015-01-01T00:06:00
true
To a solution of (S)—N-(1-hydroxypropan-2-yl)-2-nitrobenzenesulfonamide (6.20 kg, 23.8 mol) in methylene chloride (32 L) was added 4-methylmorpholine (3.13 kg, 30.9 mol) at an internal temperature of 10° C. or below. The resulting reaction mixture was cooled to 0° C., and added a solution of methanesulfonyl chloride (3.27 kg, 28.5 mol) in methylene chloride (2 L) at an internal temperature of −5° C. to 0° C. Subsequently, the reaction mixture was stirred at room temperature for 20 hours. After confirming the disappearance of the starting materials by TLC, purified water was added to the reaction mixture. The resulting organic layer was partitioned, washed with saturated brine, dried over magnesium sulfate, and filtered. The filtrate was then concentrated under reduced pressure to give the target product as a yellow solid (7.30 kg, yield 90.70).
C[C@@H](COS(C)(=O)=O)NS(=O)(=O)c1ccccc1[N+](=O)[O-]
null
CS(=O)(=O)Cl
C[C@@H](CO)NS(=O)(=O)c1ccccc1[N+](=O)[O-]
null
[OH:1][CH2:2][C@@H:3]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16])(=[O:8])=[O:7])[CH3:4].CN1CCOCC1.[CH3:25][S:26](Cl)(=[O:28])=[O:27]>C(Cl)Cl>[CH3:25][S:26]([O:1][CH2:2][C@@H:3]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16])(=[O:7])=[O:8])[CH3:4])(=[O:28])=[O:27]
20
ClCCl
CN1CCOCC1
null
0
90.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
822,345
[Pd]
null
null
null
ord_dataset-ec58fad8331a42c5a67ad75aac6713b4
2008-01-01T00:05:00
true
To a solution of benzyl 1-[2-[4-(5-methylpiridin-2-yl-amino)piperidin-1-yl]ethyl]cyclohexanecarboxylate (160 mg, 0.37 mmol) in ethanol (16 mL) was added 10% palladium carbon (80 mg) at room temperature. The mixture was stirred at room temperature under hydrogen atmosphere for 24 hours. Acetic acid was added to the mixture, and it was filtered with Celite and concentrated under reduced pressure. Methanol and diethyl ether were added to the residue, and the solution was stirred under ice cooling for 1 hour. The crystals were recovered by filtration to give the title compound (100 mg).
Cc1ccc(NC2CCN(CCC3(C(=O)O)CCCCC3)CC2)nc1
null
Cc1ccc(NC2CCN(CCC3(C(=O)OCc4ccccc4)CCCCC3)CC2)nc1
null
null
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][C:17]3([C:23]([O:25]CC4C=CC=CC=4)=[O:24])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[CH2:11][CH2:10]2)=[N:6][CH:7]=1.C(O)(=O)C>C(O)C.[C].[Pd]>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][C:17]3([C:23]([OH:25])=[O:24])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[CH2:11][CH2:10]2)=[N:6][CH:7]=1
24
CC(=O)O
CCO
null
25
78.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
292,536
[Na+]
[OH-]
null
null
ord_dataset-6c3ec086c8c9475e8d31a44641b49e02
1994-01-01T00:06:00
true
A solution of 0.56 g (1.11 mol) of N-(2-methoxy-2-oxoethyl)-N-[3-(octadecyloxy)phenyl]glycine methyl ester and 4.4 ml (4.4 mmol) of 1N NaOH in 50 ml of methanol was stirred at reflux under argon atmosphere for 75 minutes. After standing at room temperature for 17 hours the precipitate was removed by filtration. The solid was suspended in 100 ml of 1N HCl and extracted with ethyl acetate. The dried extract was concentrated at reduced pressure and the resultant solid was recrystallized from methanol-water to give 0.31 g (60% yield, mp 135°-138°) of N-(carboxymethyl)-N-[3-(octadecyloxy)phenyl]glycine.
CCCCCCCCCCCCCCCCCCOc1cccc(N(CC(=O)O)CC(=O)O)c1
null
CCCCCCCCCCCCCCCCCCOc1cccc(N(CC(=O)OC)CC(=O)OC)c1
null
null
C[O:2][C:3](=[O:36])[CH2:4][N:5]([CH2:31][C:32]([O:34]C)=[O:33])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH:7]=1.[OH-].[Na+]>CO>[C:3]([CH2:4][N:5]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH:7]=1)[CH2:31][C:32]([OH:34])=[O:33])([OH:36])=[O:2]
17
CO
null
null
null
0.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,512,598
[Zn]
null
null
null
ord_dataset-1a1aa5d1c3224edca0aec6e3398da985
2014-01-01T00:11:00
true
Zinc dust (9.3 g, 142 mmol) was added to a stirred solution of N-[5-(4-fluoro-phenyl)-3-nitro-pyridin-2-yl]-benzene-1,3-diamine (2.3 g, 7.1 mmol) in AcOH (35 ml) at RT. After the exotherm had subsided the reaction was stirred and heated at 60° C. for 3 hours. The mixture was allowed to cool to RT then filtered through Celite—washing with AcOH (˜150 ml). The filtrate was evaporated and the residue was azeotroped with toluene (×2). The residue was taken up in trimethylorthoformate (50 ml) and then stirred and heated at reflux under N2 for 1 hour. After cooling to RT, the volatiles were removed in vacuo. The residue was taken up in EtOH (100 ml). c. HCl (4 ml) was added and the mixture was heated at reflux for 2 hours. After cooling, the mixture was concentrated to ˜4 ml and basified with saturated aqueous NaHCO3. The aqueous mixture was extracted with CH2Cl2 (×3). The combined extracts were dried (MgSO4), filtered and evaporated. The residue was purified by chromatography on silica (40→100% EtOAc/petrol) to give the title compound (0.86 g).
Nc1cccc(-n2cnc3cc(-c4ccc(F)cc4)cnc32)c1
null
CC(=O)O
Nc1cccc(Nc2ncc(-c3ccc(F)cc3)cc2[N+](=O)[O-])c1
null
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([N+:22]([O-])=O)[C:11]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[CH:16]=3)=[N:12][CH:13]=2)=[CH:4][CH:3]=1.[CH3:25]C(O)=O>[Zn]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[N:22]=[CH:25][N:14]([C:15]4[CH:16]=[C:17]([NH2:21])[CH:18]=[CH:19][CH:20]=4)[C:11]3=[N:12][CH:13]=2)=[CH:4][CH:3]=1
null
null
null
null
60
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
395,596
[Na+]
[OH-]
null
null
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
1998-01-01T00:03:00
true
To a stirred solution of sodium hydroxide (0.35 g, 8.8 mM) in methanol (31 mL) was added 5-iodo-2H-3,1-benzoxazine-2,4(1H)-dione (18.5 g, 64.0 mM). The mixture was heated at 60° C. for 1.5 hr. An additional quantitiy of sodium hydroxide (0.10 g, 2.5 mM) was added to the reaction mixture and stirring at 60° C. was continued for an additonal 1 hr. After cooling to room temperature, the reaction mixture was concentrated and the residue was taken up in ethyl acetate. The ethyl acetate was washed successively with water, brine, dilute aqueous sodium hydroxide, and water. After drying over MgSO4, the ethyl acetate was filtered and concentrated to leave (13.9 g, 78.4%) of the title ester as a brown oil; MS(CI): 278 (M+H).
COC(=O)c1c(N)cccc1I
null
O=c1[nH]c2cccc(I)c2c(=O)o1
null
null
[OH-].[Na+].[I:3][C:4]1[C:9]2[C:10](=[O:15])[O:11][C:12](=O)[NH:13][C:8]=2[CH:7]=[CH:6][CH:5]=1>CO.[OH-].[Na+]>[NH2:13][C:8]1[CH:7]=[CH:6][CH:5]=[C:4]([I:3])[C:9]=1[C:10]([O:11][CH3:12])=[O:15]
1
CO
null
null
60
78.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
504,176
Cl
null
null
null
ord_dataset-d673d02cdac14dba9ff59f12845a4f37
2001-01-01T00:05:00
true
A solution of 0.51 g of (E)-2(R)-[1(S)-[(tetrahydro-2(RS)-pyranyloxy)carbamoyl]-4-phenyl-3-butenyl]-2′-isobutyl-4-methyl-2′-(2-ureidoacetyl)valerohydrazide dissolved in 5 ml of 4M hydrogen chloride in dioxan was stirred for 2 hours at room temperature and diluted with diethyl ether. The solid was filtered off, washed with diethyl ether and dried to give 0.36 g of (E)-2(R)-[1(S)-(hydroxycarbamoyl)-4-phenyl-3-butenyl]-2′-isobutyl-4-methyl-2′-(2-ureidoacetyl)valerohydrazide in the form of a white solid.
CC(C)C[C@@H](C(=O)NN(CC(C)C)C(=O)CNC(N)=O)[C@H](C/C=C/c1ccccc1)C(=O)NO
null
CC(C)C[C@@H](C(=O)NN(CC(C)C)C(=O)CNC(N)=O)[C@H](C/C=C/c1ccccc1)C(=O)NOC1CCCCO1
null
null
O1CCCCC1[O:7][NH:8][C:9]([C@H:11]([C@@H:21]([CH2:37][CH:38]([CH3:40])[CH3:39])[C:22]([NH:24][N:25]([CH2:33][CH:34]([CH3:36])[CH3:35])[C:26](=[O:32])[CH2:27][NH:28][C:29]([NH2:31])=[O:30])=[O:23])[CH2:12]/[CH:13]=[CH:14]/[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:10]>Cl.O1CCOCC1.C(OCC)C>[OH:7][NH:8][C:9]([C@H:11]([C@@H:21]([CH2:37][CH:38]([CH3:40])[CH3:39])[C:22]([NH:24][N:25]([CH2:33][CH:34]([CH3:35])[CH3:36])[C:26](=[O:32])[CH2:27][NH:28][C:29]([NH2:31])=[O:30])=[O:23])[CH2:12]/[CH:13]=[CH:14]/[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:10]
2
CCOCC
C1COCCO1
null
25
null
83.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
149,725
N
[Cl-]
[NH4+]
null
ord_dataset-f222e615b1f74f0fabef9cd9b98516b7
1986-01-01T00:10:00
true
A mixture of liquid NH3 (400 mL) and catalytic Fe(NO3)3 was stirred under N2 at -50° C. A small portion of Na metal (from a total amount of 20 g., 0.87 mole) was added. Air was bubbled through the reaction mixture briefly until a black precipitate appeared. The remaining Na was added portionwise. 3-(6-bromo-2,3-dimethoxyphenyl)-propionitrile (31.1 g, 0.115 mole) was added over 70 minutes as the reaction mixture was stirred at slow reflux. When the addition was complete, the reaction mixture was stirred at reflux for 1/2 hr, then was cooled to -55° C. as NH4Cl (35.2 g, 0.66 mole) was added slowly. NH3 was allowed to evaporate overnight. Water was added cautiously with stirring. The solid was filtered, washed with water, dried (in-vacuo) to yield 21.0 g gray powder, (97%); M+ 189.
COc1ccc2c(c1OC)CC2C#N
null
COc1ccc(Br)c(CCC#N)c1OC
null
null
Br[C:2]1[C:7]([CH2:8][CH2:9][C:10]#[N:11])=[C:6]([O:12][CH3:13])[C:5]([O:14][CH3:15])=[CH:4][CH:3]=1.[NH4+].[Cl-]>N>[CH3:13][O:12][C:6]1[C:7]2[CH2:8][CH:9]([C:10]#[N:11])[C:2]=2[CH:3]=[CH:4][C:5]=1[O:14][CH3:15]
null
null
null
null
-50
null
96.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
374,844
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
null
null
null
ord_dataset-ee5599340390470d8e5b5ac1feddf9d6
1997-01-01T00:08:00
true
4.6 g of ethyl 5-bromo-1-(2,4-difluorophenyl)-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate, 4.5 g of tributylvinylstannane and 0.46 g of tetrakis(triphenylphosphine)palladium(0) are refluxed for 10 hours in 40 ml of absolute toluene under a nitrogen atmosphere. The product is filtered off with suction at room temperature, washed with water and dried. 2.7 g of the title compound are obtained (66% of theory).
C=Cc1c(F)c(F)c(F)c2c1c(=O)c(C(=O)OCC)cn2-c1ccc(F)cc1F
null
CCCCC([SnH3])=C(CCCC)CCCC
CCOC(=O)c1cn(-c2ccc(F)cc2F)c2c(F)c(F)c(F)c(Br)c2c1=O
null
Br[C:2]1[C:11]([F:12])=[C:10]([F:13])[C:9]([F:14])=[C:8]2[C:3]=1[C:4](=[O:28])[C:5]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:6][N:7]2[C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=1[F:22].[CH2:29](C([SnH3])=C(CCCC)CCCC)[CH2:30]CC>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>[F:22][C:16]1[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:15]=1[N:7]1[C:8]2[C:3](=[C:2]([CH:29]=[CH2:30])[C:11]([F:12])=[C:10]([F:13])[C:9]=2[F:14])[C:4](=[O:28])[C:5]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:6]1
null
Cc1ccccc1
null
null
null
null
66.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,110,303
[BH3-]C#N
[Na+]
null
null
ord_dataset-375a420ee9b042918ddca20f02df37d3
2011-01-01T00:11:00
true
To a 25° C. solution of 4-(5-aminomethyl-naphthalene-1-sulfonylamino)-piperidine-1-carboxylic acid ethyl ester 55 (62 mg, 0.159 mmol) in MeOH (4 mL) was added 4-chloro-benzaldehyde (45 mg, 0.318 mmol) and sodium cyanoborohydride (50 mg, 0.795 mmol). After stirring for 2 h at 25° C., the solution was concentrated in vacuo and the resultant crude material was purified by reverse phase HPLC to provide the title compound (H-45) as its formate salt. 1H NMR (300 MHz, MeOD) δ 8.78 (d, 1H), 8.38 (s, 1H), 8.33 (m, 2H), 7.70 (m, 3H), 7.45 (m, 4H), 4.57 (s, 2H), 4.20 (s, 2H), 4.05 (q, 2H), 3.75 (d, 2H), 3.20 (m, 1H), 2.75 (m, 2H), 1.50 (m, 2H), 1.25 (m, 2H), 1.17 (t, 3H); LC/MS m/z 516 (M+H)+.
CCOC(=O)N1CCC(NS(=O)(=O)c2cccc3c(CNCc4ccc(Cl)cc4)cccc23)CC1
O=C[O-]
O=Cc1ccc(Cl)cc1
CCOC(=O)N1CCC(NS(=O)(=O)c2cccc3c(CN)cccc23)CC1
null
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][CH:9]([NH:12][S:13]([C:16]2[C:25]3[C:20](=[C:21]([CH2:26][NH2:27])[CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH2:8][CH2:7]1)=[O:5])[CH3:2].[Cl:28][C:29]1[CH:36]=[CH:35][C:32]([CH:33]=O)=[CH:31][CH:30]=1.C([BH3-])#N.[Na+]>CO>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][CH:9]([NH:12][S:13]([C:16]2[C:25]3[C:20](=[C:21]([CH2:26][NH:27][CH2:33][C:32]4[CH:35]=[CH:36][C:29]([Cl:28])=[CH:30][CH:31]=4)[CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)(=[O:14])=[O:15])[CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH:4]([O-:5])=[O:3]
2
CO
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
227,554
O=C(n1ccnc1)n1ccnc1
null
null
null
ord_dataset-d98d003e9abb4b579746c5a361466e14
1991-01-01T00:05:00
true
A solution of 6-oxo-6-(2-phenylethylamino)hexanoic acid (2.49 g) and carbonyldiimidazole (1.62 g) in dry dichloromethane (100 ml) was stirred under a nitrogen atmosphere for 2 hours at room temperature. A solution of 1,2,3,4-tetrahydro-5,6-dimethoxy-2- aminonaphthalene (2.07 g) in dichloromethane (20 ml) was added and the solution stirred at room temperature for 18 hours. The solution was washed with dilute hydrochloric acid, dilute sodium carbonate solution and water. The organic phase was separated, dried over magnesium sulfate, filtered and evaporated to leave the sub-title compound which crystallised from isopropanol as colorless flakes (3.8 g), m.p. 191°-193°.
COc1ccc2c(c1OC)CCC(NC(=O)CCCCC(=O)NCCc1ccccc1)C2
null
O=C(O)CCCCC(=O)NCCc1ccccc1
COc1ccc2c(c1OC)CCC(N)C2
null
[O:1]=[C:2]([NH:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:3][CH2:4][CH2:5][CH2:6][C:7](O)=[O:8].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:31][O:32][C:33]1[C:42]([O:43][CH3:44])=[CH:41][CH:40]=[C:39]2[C:34]=1[CH2:35][CH2:36][CH:37]([NH2:45])[CH2:38]2>ClCCl>[CH3:31][O:32][C:33]1[C:42]([O:43][CH3:44])=[CH:41][CH:40]=[C:39]2[C:34]=1[CH2:35][CH2:36][CH:37]([NH:45][C:7](=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][C:2]([NH:10][CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:1])[CH2:38]2
18
ClCCl
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,054,125
Cc1ccc(S(=O)(=O)O)cc1
null
null
null
ord_dataset-373415d3e0e54004837cf4831e67666f
2011-01-01T00:05:00
true
4-[(4-Amino-3-nitrophenyl)oxy]-3-chlorobenzaldehyde (1.16 g, 5.3 mmol), ethylene glycol (5 ml) and p-toluenesulfonic acid (50 mg) in 150 mL of toluene was heated at 120 degrees centigrade with a Dean-Stark trap for 24 hours. The reaction mixture was diluted with ethyl acetate and washed twice with 1N NaOH. The organic layer was dried over MgSO4 and concentrated to give 4-{[2-chloro-4-(1,3-dioxolan-2-yl)phenyl]oxy}-2-nitroaniline. (M+1) 336.9, 2.60 min (LC/MS method B)
Nc1ccc(Oc2ccc(C3OCCO3)cc2Cl)cc1[N+](=O)[O-]
null
OCCO
Nc1ccc(Oc2ccc(C=O)cc2Cl)cc1[N+](=O)[O-]
null
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:16]=[CH:15][C:12]([CH:13]=[O:14])=[CH:11][C:10]=2[Cl:17])=[CH:4][C:3]=1[N+:18]([O-:20])=[O:19].[CH2:21](O)[CH2:22][OH:23].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:17][C:10]1[CH:11]=[C:12]([CH:13]2[O:23][CH2:22][CH2:21][O:14]2)[CH:15]=[CH:16][C:9]=1[O:8][C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([N+:18]([O-:20])=[O:19])[CH:4]=1
null
CCOC(C)=O
Cc1ccccc1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,530,909
null
null
null
null
ord_dataset-8d5c200bca27407ab9febe7598e16458
2015-01-01T00:01:00
true
In a glass flask provided with a condenser, thermometer, mechanical stirrer and nitrogen inlet, —under nitrogen flow—15.0 g of 3-chloro-4-[(2-fluorobenzyl)oxy]aniline of formula (IV), 17.49 g of 4-chloro-6-iodoquinazoline of formula (VIII) (available in the market), 300 mL of Isopropanol were introduced. The reaction mixture was stirred at 70° C. for 2 hrs. Upon completing the reaction cooling was carried out at ambient temperature. The formed yellow solid was filtered washing the solid with 20 mL of cold Isopropanol. 31.9 g of product equivalent to a 98.7% molar yield were obtained. 1H-NMR spectrum according to FIG. 5.
Cl
Fc1ccccc1COc1ccc(Nc2ncnc3ccc(I)cc23)cc1Cl
Nc1ccc(OCc2ccccc2F)c(Cl)c1
Clc1ncnc2ccc(I)cc12
null
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[F:17])[NH2:5].Cl[C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([I:29])[CH:27]=2)[N:22]=[CH:21][N:20]=1>C(O)(C)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([I:29])[CH:27]=3)[N:22]=[CH:21][N:20]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[F:17]
2
CC(C)O
null
null
70
197.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,129,812
[K+]
null
null
null
ord_dataset-285df12e34cd46e993e3c8ebc3a8962a
2012-01-01T00:01:00
true
To a solution of 3-chloro-N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)-propane-1-sulfonamide (69.4 mg, 0.138 mmol) in a mixture of 8 ml 1,4-dioxane and 2 ml H2O was added KOH powder (0.674 g, 12.0 mmol) and the mixture was heated to the reflux temperature for 3 days. It was extracted using EtOAc/brine, the organic fraction was dried with Na2SO4 and the volatiles were removed. The residue was purified using flash-column chromatography (Si, DCM/MeOH 5:1, Rf=0.3). Yield: 41 mg (62%). 1H-NMR (500 MHz, MeOH [d4]): δ=7.38-7.21 (d, 1H), 7.23-7.21 (d, 1H), 7.06-7.00 (q, 1H), 6.52-6.50 (m, 1H), 6.17-6.13 (t, 1H), 3.30-3.27 (t, 2H), 2.86-2.83 (t, 2H), 2.05-2.00 (m, 2H); m/z=485 [M−1]−.
O=S(=O)(CCCO)Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F
null
O=S(=O)(CCCCl)Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F
[OH-]
null
Cl[CH2:2][CH2:3][CH2:4][S:5]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[C:11]([F:16])[C:10]=1[NH:17][C:18]1[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:19]=1[F:25])(=[O:7])=[O:6].[OH-:26].[K+]>O1CCOCC1.O>[F:16][C:11]1[C:10]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([I:24])=[CH:20][C:19]=2[F:25])=[C:9]([NH:8][S:5]([CH2:4][CH2:3][CH2:2][OH:26])(=[O:7])=[O:6])[CH:14]=[CH:13][C:12]=1[F:15]
null
O
C1COCCO1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
858,497
[N-]=[N+]=NC[C@H]1CN(c2cc(F)c(N3CCS(=O)(=O)CC3)c(F)c2)C(=O)O1
null
null
null
ord_dataset-93908aaae836460ebd48d733eccad483
2009-01-01T00:01:00
true
A suspension of (5R) 3-[3,5-difluoro-4-(1,1-dioxo-4-thiomorpholinyl)phenyl]-5-(azidomethyl)-oxazolidin-2-one (Intermediate 10) (0.82 g, 2.11 mmol) and polystyrene triphenylphosphine (5.6 g, 8.5 mmol) was reacted as described for Example 9 to give the intermediate amine, (5R)-3-[4-(1,1-Dioxo-4-thiomorpholinyl)-3,5-difluorophenyl]-5-(aminomethyl)-oxazolidin-2-one (0.65 g), which was used directly for the next step. This amine (0.63 g, 1.75 mmol) was reacted with diisopropylethylamine (0.9 ml, 5.2 mmol) and α,α-dichloroacetone tosylhydrazone (0.77 g, 2.62 mmol) as described for Example 3. Chromatography on silica gel eluting with 5% methanol in dichloromethane gave the title compound (350 mg).
NC[C@@H]1CN(c2cc(F)c(N3CCS(=O)(=O)CC3)c(F)c2)C(=O)O1
null
[N-]=[N+]=NCC1CN(c2cc(F)c(N3CCS(=O)(=O)CC3)c(F)c2)C(=O)O1
null
null
[F:1][C:2]1[CH:3]=[C:4]([N:17]2[CH2:21][CH:20]([CH2:22][N:23]=[N+]=[N-])[O:19][C:18]2=[O:26])[CH:5]=[C:6]([F:16])[C:7]=1[N:8]1[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[CH2:10][CH2:9]1.N(C[C@@H]1OC(=O)N(C2C=C(F)C(N3CCS(=O)(=O)CC3)=C(F)C=2)C1)=[N+]=[N-]>>[O:15]=[S:11]1(=[O:14])[CH2:10][CH2:9][N:8]([C:7]2[C:6]([F:16])=[CH:5][C:4]([N:17]3[CH2:21][C@@H:20]([CH2:22][NH2:23])[O:19][C:18]3=[O:26])=[CH:3][C:2]=2[F:1])[CH2:13][CH2:12]1
null
null
null
null
null
85.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
133,159
null
null
null
null
ord_dataset-34cf5f1378de4e34844aea93a2f9a9d3
1985-01-01T00:08:00
true
2.98 g of ethyl 3-(4-chlorobenzoylamino)-3-acetylpropionate, 15 ml of dimethylformamide and 1.8 g of phosphorus oxychloride are treated in the same manner as described in Example 1. 1.98 g of ethyl 2-[2-(4-chlorophenyl)-5-methyl-4-oxazolyl]acetate are thereby obtained. Yield: 70.9%.
CCOC(=O)Cc1nc(-c2ccc(Cl)cc2)oc1C
null
CCOC(=O)CC(NC(=O)c1ccc(Cl)cc1)C(C)=O
null
null
[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([C:6]([NH:8][CH:9]([C:16](=[O:18])[CH3:17])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=O)=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O>CN(C)C=O>[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([C:6]2[O:18][C:16]([CH3:17])=[C:9]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:8]=2)=[CH:4][CH:3]=1
null
CN(C)C=O
O=P(Cl)(Cl)Cl
null
null
null
70.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
671,066
null
null
null
null
ord_dataset-e90cd41afe844e49875435eb99903799
2005-01-01T00:05:00
true
A mixture of N-(6-chloro-pyrazin-2-yl)-acetamide I-5a (58.6 mg, 0.34 mmol) and piperazine-1-carboxylic acid tert-butyl ester (636 mg, 3.42 mmol) in ethanol (2 mL) was stirred at reflux for 24 h. The reaction mixture was diluted with ethyl acetate (40 mL) and washed with 0.1M HCl (3×35 mL), brine, dried (Na2SO4), filtered, and evaporated to dryness. The crude residue was purified by preparative TLC using ethyl acetate as the eluant to afford the title compound I-5b (36.9 mg).
CC(=O)Nc1cncc(N2CCN(C(=O)OC(C)(C)C)CC2)n1
null
CC(C)(C)OC(=O)N1CCNCC1
CC(=O)Nc1cncc(Cl)n1
null
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:11])[CH3:10])[CH:5]=[N:4][CH:3]=1.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]>C(O)C.C(OCC)(=O)C>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([NH:8][C:9](=[O:11])[CH3:10])[N:7]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]
null
CCOC(C)=O
CCO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
394,099
Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
[Cl-]
[Na+]
null
ord_dataset-018fd0e1351f4fd09b20fcddd97b4c7a
1998-01-01T00:03:00
true
To a solution of 4-ethynylbenzonitrile (0.5 g), 2-bromo-5-nitrothiophene (0.9 g) and bis(triphenylphosphine)palladium dichloride (83 mg) in anhydrous dimethylformamide (4 ml) was added triethylamine (2.2 ml). The reaction mixture was stirred at room temperature for 3 days then ethyl acetate (200 ml) and saturated sodium chloride (200 ml) were added. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to dryness. The crude solid was triturated with 1:1 dichloromethane/hexane followed by diethyl ether to give 4-[(5-nitro-2-thienyl)ethynyl]benzonitrile as a yellow solid.
N#Cc1ccc(C#Cc2ccc([N+](=O)[O-])s2)cc1
null
O=[N+]([O-])c1ccc(Br)s1
C#Cc1ccc(C#N)cc1
null
[C:1]([C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1)#[CH:2].Br[C:12]1[S:13][C:14]([N+:17]([O-:19])=[O:18])=[CH:15][CH:16]=1.C(N(CC)CC)C.[Cl-].[Na+]>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C>[N+:17]([C:14]1[S:13][C:12]([C:2]#[C:1][C:3]2[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=2)=[CH:16][CH:15]=1)([O-:19])=[O:18]
72
CCOC(C)=O
CCN(CC)CC
CN(C)C=O
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
700,440
[Li+]
[OH-]
null
null
ord_dataset-bbd7e53f000345838ad4920a07a169ff
2006-01-01T00:03:00
true
To an ice cold solution of methyl N-(4-bromo-3-methylisothiazol-5-yl)-L-leucinate (11.7 g, 36.4 mmol) in methanol (300 mL) was slowly added over 10 min a 2.0 M aqueous lithium hydroxide solution (75 mL, 150 mmol). The resulting cloudy solution was stirred at room temperature for 3 hours. Most of the methanol was removed under reduced pressure and the resulting aqueous suspension was partitioned between EtOAc and water+90 ml of 10% HCl. The organic layer was washed once with water, dried over Na2SO4 and concentrated in vacuo to give N-(4-bromo-3-methylisothiazol-5-yl)-L-leucine as a white solid.
Cc1nsc(N[C@@H](CC(C)C)C(=O)O)c1Br
null
COC(=O)[C@H](CC(C)C)Nc1snc(C)c1Br
null
null
[Br:1][C:2]1[C:3]([CH3:17])=[N:4][S:5][C:6]=1[NH:7][C@H:8]([C:13]([O:15]C)=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11].[OH-].[Li+]>CO>[Br:1][C:2]1[C:3]([CH3:17])=[N:4][S:5][C:6]=1[NH:7][C@H:8]([C:13]([OH:15])=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11]
3
CO
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,690,539
[Li]O
null
null
null
ord_dataset-c1e70ad912eb438f8d34b1dc681f809a
2016-01-01T00:02:00
true
A mixture of 113a (80 mg, 0.115 mmol) and LiOH.H2O (24 mg, 0.573 mmol) in THF/i-PrOH/water (3.0 mL/1.0 mL/1.0 mL) was stirred at rt for 6 h. The mixture was extracted with EA. The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by prep-TLC (EA/MeOH=25/1) to give 113 (50 mg, 67%) as white solid. 1H NMR (300 MHz, DMSO-d6, 80° C.): δ 8.42 (s, 2H), 8.35 (s, 1H), 7.52 (t, J=8.1 Hz, 1H), 7.43 (d, J=2.4 Hz, 1H), 7.33-7.30 (m, 2H), 6.81 (d, J=8.1 Hz, 1H), 6.68-6.59 (m, 1H), 6.19 (d, J=8.1 Hz, 1H), 6.05-5.99 (m, 1H), 5.56 (m, 1H), 4.37-4.32 (m, 2H), 3.68 (t, J=5.4 Hz, 2H), 3.62 (s, 3H), 3.07 (s, 3H), 2.95-2.86 (m, 6H), 1.91-1.89 (m, 4H). ESI-LCMS: m/z=657.3 [C34H33FN6O5S+H]+
C=CC(=O)N(C)CCOc1cccc(Nc2cc(-c3cc(F)cc(-n4ncc5c6c(sc5c4=O)CCCC6)c3CO)cn(C)c2=O)n1
null
C=CC(=O)N(C)CCOc1cccc(Nc2cc(-c3cc(F)cc(-n4ncc5c6c(sc5c4=O)CCCC6)c3COC(C)=O)cn(C)c2=O)n1
null
null
[F:1][C:2]1[CH:3]=[C:4]([N:37]2[C:42](=[O:43])[C:41]3[S:44][C:45]4[CH2:50][CH2:49][CH2:48][CH2:47][C:46]=4[C:40]=3[CH:39]=[N:38]2)[C:5]([CH2:32][O:33]C(=O)C)=[C:6]([C:8]2[CH:9]=[C:10]([NH:16][C:17]3[N:22]=[C:21]([O:23][CH2:24][CH2:25][N:26]([CH3:31])[C:27](=[O:30])[CH:28]=[CH2:29])[CH:20]=[CH:19][CH:18]=3)[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=1.O[Li].O>C1COCC1.CC(O)C.O>[F:1][C:2]1[CH:3]=[C:4]([N:37]2[C:42](=[O:43])[C:41]3[S:44][C:45]4[CH2:50][CH2:49][CH2:48][CH2:47][C:46]=4[C:40]=3[CH:39]=[N:38]2)[C:5]([CH2:32][OH:33])=[C:6]([C:8]2[CH:9]=[C:10]([NH:16][C:17]3[N:22]=[C:21]([O:23][CH2:24][CH2:25][N:26]([CH3:31])[C:27](=[O:30])[CH:28]=[CH2:29])[CH:20]=[CH:19][CH:18]=3)[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=1
6
C1CCOC1
CC(C)O
O
25
null
66.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,629,447
CC(C)(C)OC(=O)N1CCC(O)CC1
O=C([O-])[O-]
[Na+]
null
ord_dataset-f0794d5ded7a4d3fab45cc3d7a89ee3d
2015-01-01T00:09:00
true
To a solution consisting of 2-phenyl-5-(2H-tetrazol-5-yl)pyrimidine (25 mg, 0.111 mmol) in DMF (2.0 mL) was added tert-butyl 4-(tosyloxy)piperidine-1-carboxylate (40 mg, 0.111 mmol), synthesized from tert-butyl 4-hydroxypiperidine-1-carboxylate (PCT International Application No. WO 2007/060026), and sodium carbonate (85 mg, 0.45 mmol). The suspension was vigorously stirred for 24 hours and an additional molar equivalent of tert-butyl 4-(tosyloxy)piperidine-1-carboxylate was added and the reaction was heated for another 24 hours at 70° C. After cooling to room temperature, the crude reaction mixture was diluted with ethyl acetate, washed sequentially with 1 M sodium carbonate, 5% citric acid, and brine. After solvent evaporation, the remaining crude solid was dissolved in a minimal amount of dichloromethane and purified by flash silica column chromatography. Elution through a 40-g Analogix® flash silica cartridge with 100% dichloromethane to 2% methanol in dichloromethane provided the title compound as an off-white solid. The solid was further purified by triturating with methanol to afford the title compound as a white solid (15 mg, 33% yield); Rf 0.37 with 95:2 v/v dichloromethane-methanol; melting point 178-180° C.; 1H-NMR (400 MHz; CDCl3) δ 9.47 (s, 2H), 8.52-8.49 (m, 2H), 7.52-7.50 (m, 3H), 4.96-4.95 (m, 2H), 4.23 (bs, 2H), 3.10-2.97 (m, 2H), 2.30-2.21 (m, 4H), 1.48 (s, 9H); MS (ESI+) m/z 408.2 (M+1).
CC(C)(C)OC(=O)N1CCC(n2nnc(-c3cnc(-c4ccccc4)nc3)n2)CC1
null
Cc1ccc(S(=O)(=O)OC2CCN(C(=O)OC(C)(C)C)CC2)cc1
c1ccc(-c2ncc(-c3nn[nH]n3)cn2)cc1
null
[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]3[N:14]=[N:15][NH:16][N:17]=3)=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(O[CH:29]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]1)(C1C=CC(C)=CC=1)(=O)=O.OC1CCN(C(OC(C)(C)C)=O)CC1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C(OCC)(=O)C>[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]3[N:14]=[N:15][N:16]([CH:29]4[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]4)[N:17]=3)=[CH:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
24
CN(C)C=O
CCOC(C)=O
null
70
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
213,280
O=C([O-])[O-]
[K+]
null
null
ord_dataset-b67d30cd146f49dcbf24faee022f1a09
1990-01-01T00:08:00
true
A suspension of 10.2 g of 7-chloro-2,3-dihydro-1,2-benzisothiazole-1,1-dioxide, 8.3 g of potassium carbonate and 7.7 ml of 1-iodopentane was refluxed in 50 ml of ethanol for 28 hours, cooled, concentrated and added to 200 ml of water. The mixture was extracted with n-BuCl, the extract washed with water and brine, dried over MgSO4 and concentrated to give 13.3 g of an amber oil which was triturated with hexane to give 11.4 g of the title compound as a tan powder, m.p. 46°-48° C.
CCCCCN1Cc2cccc(Cl)c2S1(=O)=O
null
O=S1(=O)NCc2cccc(Cl)c21
CCCCCI
null
[Cl:1][C:2]1[C:10]2[S:9](=[O:12])(=[O:11])[NH:8][CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].I[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]>C(O)C>[CH2:20]([N:8]1[CH2:7][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([Cl:1])[C:10]=2[S:9]1(=[O:12])=[O:11])[CH2:21][CH2:22][CH2:23][CH3:24]
null
CCO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
135,432
O=C1CCCN1
null
null
null
ord_dataset-3007013966624a1096d71142f31cb5a3
1985-01-01T00:10:00
true
Reaction of 9(R)-acetyl-6,9,11-trihydroxy-5,7,8,9,10,12-hexahydronaphthacene-5,12-dione ([α]D20 =-87° (c=0.1, CHCl3)) (11.5 g) with pyrrolidone hydrotribromide (18.19 g) was effected in tetrahydrofuran (1380 mg) at room temperature for 40 hours. After removing insoluble matters by filtration, the solvent was distilled off under reduced pressure to give 9(R)-bromoacetyl-6,9,11-trihydroxy-5,7,8,9,10,12-hexahydronaphthacene-5,12-dione, which was used in the next step without purification.
O=C1c2ccccc2C(=O)c2c(O)c3c(c(O)c21)CC[C@](O)(C(=O)CBr)C3
null
CC(=O)[C@@]1(O)CCc2c(O)c3c(c(O)c2C1)C(=O)c1ccccc1C3=O
null
null
[C:1]([C@:4]1([OH:26])[CH2:21][C:20]2[C:19]([OH:22])=[C:18]3[C:9]([C:10](=[O:24])[C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=4[C:17]3=[O:23])=[C:8]([OH:25])[C:7]=2[CH2:6][CH2:5]1)(=[O:3])[CH3:2].C1CNC(=O)C1.[Br:33][Br-]Br>O1CCCC1>[Br:33][CH2:2][C:1]([C@:4]1([OH:26])[CH2:21][C:20]2[C:19]([OH:22])=[C:18]3[C:9]([C:10](=[O:24])[C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=4[C:17]3=[O:23])=[C:8]([OH:25])[C:7]=2[CH2:6][CH2:5]1)=[O:3]
null
C1CCOC1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,008,162
O=C([O-])[O-]
[K+]
null
null
ord_dataset-7448b89163bf426c9d9777809ce24cec
2010-01-01T00:11:00
true
To a solution of 3-(3-chloro-4-isopropoxyphenyl)-5-(1,2,3,4-tetrahydroisoquinolin-5-yl)-1,2,4-oxadiazole (0.0726 g, 0.196 mmol) in DMF (1.963 ml) was added K2CO3 (0.054 g, 0.393 mmol) followed by tert-butyl bromoacetate (0.030 ml, 0.206 mmol). After about 48 h the reaction mixture was filtered, concentrated in vacuo and purified by chromatography to provide tert-butyl 2-(5-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)-3,4-dihydroisoquinolin-2(1H)-yl)acetate as a colorless oil that solidified on standing. LCMS (Table 1, Method c) Rt=3.41 min, m/z 486 (M+H)+.
CC(C)Oc1ccc(-c2noc(-c3cccc4c3CCN(CC(=O)OC(C)(C)C)C4)n2)cc1Cl
null
CC(C)(C)OC(=O)CBr
CC(C)Oc1ccc(-c2noc(-c3cccc4c3CCNC4)n2)cc1Cl
null
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[N:16]=[C:15]([C:17]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:18]=3[CH2:19][CH2:20][NH:21][CH2:22]4)[O:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].C([O-])([O-])=O.[K+].[K+].Br[CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[N:16]=[C:15]([C:17]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:18]=3[CH2:19][CH2:20][N:21]([CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:22]4)[O:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]
null
CN(C)C=O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,713,743
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
null
null
null
ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb
2016-01-01T00:04:00
true
A mixture of 1-benzyl-2-bromo-5-chloro-1H-pyrrolo[3,2-b]pyridine (0.15 g, 0.47 mmol, from Example 62, Step 2) and 4-(tributylstannyl)-1-trityl-1H-imidazole (0.28 g, 0.47 mmol, Synthonix) in toluene (9.0 mL) was degassed. Tetrakis(triphenylphosphine)palladium(0) (54 mg, 0.047 mmol) was added and the reaction was stirred at 110° C. for 17 h. Solvent was removed in vacuo and the product was purified by flash chromatography, eluting with a gradient from 0-35% EtOAc in hexanes to afford product as a white solid (0.17 g, 66%).
Clc1ccc2c(cc(-c3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)n2Cc2ccccc2)n1
null
Clc1ccc2c(cc(Br)n2Cc2ccccc2)n1
CCCC[Sn](CCCC)(CCCC)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
null
[CH2:1]([N:8]1[C:16]2[C:11](=[N:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[CH:10]=[C:9]1Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:24]1[N:25]=[CH:26][N:27]([C:29]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:28]=1)CCC>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([N:8]1[C:16]2[C:11](=[N:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:24]1[N:25]=[CH:26][N:27]([C:29]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:28]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
17
Cc1ccccc1
null
null
110
null
65.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,297,436
CCN=C=NCCCN(C)C
Cl
null
null
ord_dataset-de51ecc8d4434bacaa8bc32d7d73484c
2013-01-01T00:05:00
true
A solution of 4.40 g (8.64 mmol) of (S)-4-benzyloxy-2-{2-[benzyloxycarbonyl-(2-carboxy-ethyl)-amino]-ethylamino}-butyric acid methyl ester; hydrochloride in 85 ml dichloromethane was treated with 1.20 (8.64 mmol) of triethylamine and at 0° C. with 1.99 g (10.37 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride. The cooling bath was allowed to come to room temperature and after 15 h the reaction was extracted with 10% aq. potassium hydrogensulfate solution/diethyl ether (3×). The organic phases were washed with 10% aq. potassium hydrogensulfate solution, 10% sodium chloride solution and dried over Na2SO4 to yield after evaporation of the solvent 3.74 g (95%) of the titled compound as light yellow oil. MS: 455.2 (MH+).
COC(=O)[C@H](CCOCc1ccccc1)N1CCN(C(=O)OCc2ccccc2)CCC1=O
null
COC(=O)[C@H](CCOCc1ccccc1)NCCN(CCC(=O)O)C(=O)OCc1ccccc1
null
null
[CH3:1][O:2][C:3](=[O:34])[C@@H:4]([NH:15][CH2:16][CH2:17][N:18]([C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])[CH2:19][CH2:20][C:21](O)=[O:22])[CH2:5][CH2:6][O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>ClCCl>[CH2:27]([O:26][C:24]([N:18]1[CH2:19][CH2:20][C:21](=[O:22])[N:15]([C@H:4]([C:3]([O:2][CH3:1])=[O:34])[CH2:5][CH2:6][O:7][CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:16][CH2:17]1)=[O:25])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
15
ClCCl
CCN(CC)CC
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
244,117
null
null
null
null
ord_dataset-fa3b512e2d924b9b965301ebcba6853d
1992-01-01T00:03:00
true
To a stirred mixture of 5-bromo-2,4-dichloroquinazoline (2.3 g, 8.2 mmol) and triethylamine (1.5 ml, 11 mmol) in dichloromethane (100 ml) was added ethanolamine (0.64 ml, 11 mmol), and the mixture was stirred for 30 min. The solvent was evaporated and the residue treated with a mixture of water (30 ml) and ether (20 ml) giving the title compound as a crystalline precipitate which was collected by filtration and dried, m.p. 165°-67° C.
OCCNc1nc(Cl)nc2cccc(Br)c12
null
Clc1nc(Cl)c2c(Br)cccc2n1
NCCO
null
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](Cl)=[N:5][C:6]([Cl:12])=[N:7]2.C(N(CC)CC)C.[CH2:21]([CH2:23][NH2:24])[OH:22]>ClCCl>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]([NH:24][CH2:23][CH2:21][OH:22])=[N:5][C:6]([Cl:12])=[N:7]2
0.5
ClCCl
CCN(CC)CC
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
581,706
Cl
null
null
null
ord_dataset-60f3171f0342452f8814e7f294e2be8b
2003-01-01T00:02:00
true
By the reaction in the same manner as in Example 4-(iii) using 3′-[1-hydroxy-2-methyl-1-(1-trityl-1H-imidazol-4-yl)-1-propyl][1,1′-biphenyl]-4-carbonitrile (590 mg) and pyridine hydrochloride (111 mg), the title compound (261 mg) was obtained as colorless needle crystals.
CC(C)C(O)(c1cccc(-c2ccc(C#N)cc2)c1)c1c[nH]cn1
null
CC(C)C(O)(c1cccc(-c2ccc(C#N)cc2)c1)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
null
null
[OH:1][C:2]([C:30]1[CH:31]=[C:32]([C:36]2[CH:41]=[CH:40][C:39]([C:42]#[N:43])=[CH:38][CH:37]=2)[CH:33]=[CH:34][CH:35]=1)([C:6]1[N:7]=[CH:8][N:9](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:10]=1)[CH:3]([CH3:5])[CH3:4].Cl.N1C=CC=CC=1>>[OH:1][C:2]([C:30]1[CH:31]=[C:32]([C:36]2[CH:37]=[CH:38][C:39]([C:42]#[N:43])=[CH:40][CH:41]=2)[CH:33]=[CH:34][CH:35]=1)([C:6]1[N:7]=[CH:8][NH:9][CH:10]=1)[CH:3]([CH3:4])[CH3:5]
null
c1ccncc1
null
null
null
null
78
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
581,305
Cc1ccc(S(=O)(=O)O)cc1
null
null
null
ord_dataset-60f3171f0342452f8814e7f294e2be8b
2003-01-01T00:02:00
true
The process is performed according to the operating conditions described in 1.8, starting with 300 mg (0.62 mmol) of 3-[hydroxy[2-phenyl-1-[[(phenylmethoxy)carbonyl]amino]ethyl]phosphinyl]-2-(phenylmethyl)propanoic acid synthesized in 1.7., and 219 mg (0.62 mmol) of phenylmethyl alaninate in the form of the p-toluenesulphonic acid salt. 288 mg of product are recovered (yield=71.9%).
C[C@H](NC(=O)C(Cc1ccccc1)CP(=O)(O)C(Cc1ccccc1)NC(=O)OCc1ccccc1)C(=O)OCc1ccccc1
null
C[C@H](N)C(=O)OCc1ccccc1
O=C(NC(Cc1ccccc1)P(=O)(O)CC(Cc1ccccc1)C(=O)O)OCc1ccccc1
null
[OH:1][P:2]([CH:16]([NH:24][C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([CH2:4][CH:5]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:6](O)=[O:7])=[O:3].[NH2:35][C@H:36]([C:38]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:39])[CH3:37].C1(C)C=CC(S(O)(=O)=O)=CC=1>>[OH:3][P:2]([CH2:4][CH:5]([CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:6]([NH:35][C@H:36]([C:38]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:39])[CH3:37])=[O:7])([CH:16]([NH:24][C:25]([O:27][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:26])[CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:1]
null
null
null
null
null
71.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
181,184
null
null
null
null
ord_dataset-ed5a3d1f8dc744759e7fa1c320a44e59
1988-01-01T00:11:00
true
As described in Example 99, (E)-3-(4-methoxyphenyl)-2-butenal (8 g) was treated with (carbomethoxymethylene)triphenylphosphorane (17 g) in carbon tetrachloride (70 mL) and dichloromethane (15 mL) overnight at room temperature. The ester was isolated in the normal fashion and crystallized from hexane to afford 7.2 g of (E,E)-5-(4-methoxyphenyl)-2,4hexadienoic acid methyl ester, mp 84°-86° C.
COC(=O)/C=C/C=C(\C)c1ccc(OC)cc1
null
COc1ccc(/C(C)=C/C=O)cc1
COC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
null
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](/[C:9](/[CH3:13])=[CH:10]/[CH:11]=O)=[CH:5][CH:4]=1.[C:14]([CH:18]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:16][CH3:17])=[O:15]>C(Cl)(Cl)(Cl)Cl.ClCCl>[CH3:17][O:16][C:14](=[O:15])/[CH:18]=[CH:11]/[CH:10]=[C:9](/[C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)\[CH3:13]
null
ClCCl
ClC(Cl)(Cl)Cl
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
186,416
Cl
[Na+]
null
null
ord_dataset-754e10d30fb249229e130865010ab25b
1989-01-01T00:03:00
true
A thick suspension of the product of stage (b) (3.68 g) in conc. hydrochloric acid (50 ml) was stirred at -5° whilst a solution of sodium nitrite (0.9 g) in water (10 ml) was added dropwise so that temperature did not exceed 0°. Stirring was continued for 30 min. The resulting suspension was filtered to remove starting material and the filtrate added in a few portions to a solution of stannous chloride dihydrate (13.5 g) in hydrochloric acid (15 ml) at -20° and warmed to ambient temperature. The solid that separated was filtered off and recrystallised from hot methanol (100 ml) to give the title compound as white plates (0.39 g) m.p. 192°-193°. The mother liquors afforded a second crop (0.52 g).
NNc1ccc(CS(=O)(=O)NCc2ccccc2)cc1
null
Nc1ccc(CS(=O)(=O)NCc2ccccc2)cc1
O=N[O-]
null
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][S:9]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:11])=[O:10])=[CH:4][CH:3]=1.[N:20]([O-])=O.[Na+].[ClH:24]>O>[ClH:24].[NH:1]([C:2]1[CH:7]=[CH:6][C:5]([CH2:8][S:9]([NH:12][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)(=[O:11])=[O:10])=[CH:4][CH:3]=1)[NH2:20]
0.5
O
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,028,895
[Pd]
null
null
null
ord_dataset-83acb82dc5ba4f7aba439b9875aaac43
2011-01-01T00:02:00
true
(Method J15F) 6-[3-(1H-Indol-3-yl)-2-(4-1H-indol-3-yl-butyrylamino)-propionylamino]-hexanoic acid benzyloxy-amide (19/97) (1.654 g, 0.274 mmol) was dissolved in ethanol (20 ml), 10% Pd/C (50 mg) was added and the reaction mixture was hydrogenated at room temperature for 4 hours. The catalyst was filtered off, the solvent was evaporated and the residue was chromatographed on silica gel with acetonitrile-acetic acid (60:1) and acetonitrile-acetic acid-water (30:1:1) as eluent to give the title product (0.582 g, 41%) as white powder. M.p. 94-96° C. 1H NMR (DMSO-d6, HMDSO), δ: 1.06-1.55 (m, 6H); 1.68-1.97 (m, 4H); 2.04-2.27 (m, 2H); 2.42-2.67 (m, 2H overlapped with DMSO) 2.80-3.15 (m, 4H); 4.44-4.57 (m, 1H); 6.87-7.17 (m, 6H); 7.31 (d, 2H, J=7.6 Hz); 7.44 (d, 1H, J=7.6 Hz); 7.58 (d, 1H, J=7.6 Hz); 7.80-8.03 (m, 2H); 8.67 (s, 1H); 10.33 (s, 1H); 10.72 (s, 1H); 10.76 ppm (s, 1H). HPLC analysis on Symmetry C8 column: impurities 2.5% (column size 3.9×150 mm; mobile phase acetonitrile −0.1 M phosphate buffer (pH 2.5), 35:65; detector UV 220 nm; sample concentration 0.5 mg/ml, flow rate 1.0 ml/min). Anal. Calcd for C29H35N5O4: C, 67.29; H, 6.82; N, 13.53. Found: C, 67.06; H, 6.86; N, 13.66.
O=C(CCCCCNC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CCCc1c[nH]c2ccccc12)NO
null
O=C(CCCCCNC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CCCc1c[nH]c2ccccc12)NOCc1ccccc1
null
null
C([O:8][NH:9][C:10](=[O:45])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH:16][C:17](=[O:44])[C@@H:18]([NH:29][C:30](=[O:43])[CH2:31][CH2:32][CH2:33][C:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[NH:36][CH:35]=1)[CH2:19][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[NH:22][CH:21]=1)C1C=CC=CC=1>C(O)C.[Pd]>[OH:8][NH:9][C:10](=[O:45])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH:16][C:17](=[O:44])[C@@H:18]([NH:29][C:30](=[O:43])[CH2:31][CH2:32][CH2:33][C:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[NH:36][CH:35]=1)[CH2:19][C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[NH:22][CH:21]=1
4
CCO
null
null
null
410.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
553,201
null
null
null
null
ord_dataset-ec9decb576c4424c9685993f6262bd9c
2002-01-01T00:07:00
true
Using a procedure similar to Example 33A and 33B except starting from 2-hydroxyaniline, p-anisoyl chloride and 3-cyanobenzyl bromide, the title compound was obtained as a solid (700 mg, 48%); MS(FD): 358.1.
COc1ccc(C(=O)Nc2ccccc2OCc2cccc(C#N)c2)cc1
null
Nc1ccccc1O
N#Cc1cccc(CBr)c1
COc1ccc(C(=O)Cl)cc1
[OH:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[C:9](Cl)(=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1.[C:20]([C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH2:25]Br)#[N:21]>>[C:20]([C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH2:25][O:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH:4][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1)#[N:21]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
696,436
null
null
null
null
ord_dataset-a7baa616c65d42559e25ca0ba61e0744
2006-01-01T00:01:00
true
Following the procedure for the preparation of (1R,2S)-1-[(3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol but substituting 6-methoxy-1,2,3,4-tetrahydronaphthalen-1-amine and making non-critical variations provided the title compound as a oil: HRMS (FAB) calcd for C19H25N3O+H 312.2076, found 312.2075; Anal. Calcd for C19H25N3O: C, 73.28; H, 8.09; N, 13.49. Found C, 73.38; H, 8.11; N, 13.32.
CCc1cnc(CC)c(NC2CCCc3cc(OC)ccc32)n1
null
COc1ccc2c(c1)CCCC2N
CCc1cnc(CC)c(N[C@@H]2c3ccccc3C[C@@H]2O)n1
null
[CH2:1]([C:3]1[C:4](N[C@@H]2C3C(=CC=CC=3)C[C@@H]2O)=[N:5][C:6]([CH2:9][CH3:10])=[CH:7][N:8]=1)[CH3:2].[CH3:22][O:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[CH:30]([NH2:34])[CH2:29][CH2:28][CH2:27]2>>[CH2:1]([C:3]1[C:4]([NH:34][CH:30]2[C:31]3[C:26](=[CH:25][C:24]([O:23][CH3:22])=[CH:33][CH:32]=3)[CH2:27][CH2:28][CH2:29]2)=[N:5][C:6]([CH2:9][CH3:10])=[CH:7][N:8]=1)[CH3:2]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
42,082
[Na+]
[OH-]
null
null
ord_dataset-48929f64ce614f1181a555eafd7c97a6
1978-01-01T00:06:00
true
30 g (0.15 mol) of 4-chloromethyl-hydrocinnamic acid (J. Org, Chem. 26, 148 (1961) in 200 ml of water were neutralized with a 10% sodium hydroxide solution against phenol phthaline. 10% of NaOH (on the whole about 60 ml) were added dropwise, while stirring at reflux temperature, to the solution obtained in the same measure as it was consumed. When the reaction was finished, the mixture was saturated with sodium chloride, acidified with concentrated hydrochloric acid, the product precipitated was suction-filtered and washed with water. Melting point: 124°-126° C.
O=C(O)CCc1ccc(CO)cc1
null
O=C(O)c1ccccc1C(c1ccc(O)cc1)c1ccc(O)cc1
O=C(O)CCc1ccc(CCl)cc1
null
Cl[CH2:2][C:3]1[CH:13]=[CH:12][C:6]([CH2:7][CH2:8][C:9]([OH:11])=[O:10])=[CH:5][CH:4]=1.[OH-].[Na+].C1C=C(C(C2C=CC(O)=CC=2)C2C=CC([OH:29])=CC=2)C(C(O)=O)=CC=1>O>[OH:29][CH2:2][C:3]1[CH:13]=[CH:12][C:6]([CH2:7][CH2:8][C:9]([OH:11])=[O:10])=[CH:5][CH:4]=1
null
O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,615,363
Cl
null
null
null
ord_dataset-35c51552812941cda45194a013d34bb9
2015-01-01T00:08:00
true
To a solution of (S)-tert-butyl ((3-bromopyridin-2-yl)(4-(trifluoromethyl)-phenyl)methyl)carbamate (2.0 g, 4.64 mmol) in MeOH (10 mL) was added hydrogen chloride (3.48 mL, 13.91 mmol) (4.0 M in 1,4-dioxane). The reaction was stirred for 27 h at rt under N2. The reaction was concentrated in vacuo to give the amine which was used without further purification in subsequent steps. MS (ESI pos. ion) m/z: 331.0, 332.9 (M+H).
N[C@@H](c1ccc(C(F)(F)F)cc1)c1ncccc1Br
null
CC(C)(C)OC(=O)N[C@@H](c1ccc(C(F)(F)F)cc1)c1ncccc1Br
null
null
[Br:1][C:2]1[C:3]([C@@H:8]([NH:19]C(=O)OC(C)(C)C)[C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.[ClH:27]>CO>[ClH:27].[Br:1][C:2]1[C:3]([C@H:8]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:17])([F:18])[F:16])=[CH:11][CH:10]=2)[NH2:19])=[N:4][CH:5]=[CH:6][CH:7]=1
27
CO
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
128,457
[Li]CCCC
null
null
null
ord_dataset-d6b60b593b1c4668bc6843cd65a5d232
1985-01-01T00:04:00
true
A solution of 10.0 g (32.8 mmol) of (1,1'-biphenyl-4-yl)(chloromethyl)methyl(2-propoxy)silane and 3.6 ml (32.8 mmol) of 4-bromofluorobenzene in 30 ml of dry tetrahydrofuran was cooled to -60° under nitrogen and stirred while 20.5 ml (32.8 mmol) of 1.6 molar n-butyllithium in hexane was added at a rate that held the mixture below 50°. After stirring at -70° for another 30 minutes, the solution was allowed to warm to room temperature and was worked up as in Example 8. The resulting crude product was subjected to distillation at 130°-150° (0.2 mm) to remove unreacted starting material, leaving the title compound as an oil: nD23 1.5128; nmr (CDCl3): 0.7 (3H, s), 3.1 (2H, s), 7.1 (2H, t), 7.2-7.8 (11H, m).
Fc1ccc(C[SiH](CCl)c2ccc(-c3ccccc3)cc2)cc1
null
CC(C)O[Si](C)(CCl)c1ccc(-c2ccccc2)cc1
Fc1ccc(Br)cc1
null
[C:1]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:6]=[CH:5][C:4]([Si:7]([CH2:13][Cl:14])([CH3:12])OC(C)C)=[CH:3][CH:2]=1.Br[C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1.C([Li])CCC>O1CCCC1.CCCCCC>[C:1]1([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:2]=[CH:3][C:4]([SiH:7]([CH2:13][Cl:14])[CH2:12][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[CH:5][CH:6]=1
0.5
C1CCOC1
CCCCCC
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,324,704
null
null
null
null
ord_dataset-cfad8b3f00044bcda60a96b019f09872
2013-01-01T00:08:00
true
3-Bromo-2-methoxybenzoic acid (2 g, 8.65 mmol, 1.0 eq) was dissolved in dry DCM and stirred for 10 minutes, cooled to 0° C. and slowly treated with oxalyl chloride (3.3 g, 25.9 mmol, 3 eq). Methanol in pyridine was added dropwise and the reaction mixture was stirred at ambient temperature. The solvents were evaporated under reduced pressure and the reaction mass was diluted with water. The aqueous mixture was extracted with ethyl acetate. The organic layer was dried with anhydrous Na2SO4 and concentrated under vacuum to afford the desired product (1.9 g, 90%). 1H NMR (400 MHz, CDCl3) δ 3.93 (s, 6H), 7.02-6.06 (t, 1H), 7.72-7.76 (m, 2H). MS (ESI): 247.0 (M+H)+.
COC(=O)c1cccc(Br)c1OC
null
COc1c(Br)cccc1C(=O)O
O=C(Cl)C(=O)Cl
null
[Br:1][C:2]1[C:3]([O:11][CH3:12])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[C:13](Cl)(=O)C(Cl)=O.CO>C(Cl)Cl.N1C=CC=CC=1>[Br:1][C:2]1[C:3]([O:11][CH3:12])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([O:7][CH3:13])=[O:6]
0.17
c1ccncc1
ClCCl
CO
0
89.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
505,816
[Cl-]
[Li]CCCC
[NH4+]
null
ord_dataset-631d58dab387485c8eb0db4c20a232b7
2001-01-01T00:06:00
true
To a solution of diisopropylamine (1.33 ml) in tetrahydrofuran (20 ml) is added gradually and dropwise a 1.6 N solution of n-butyl lithium in hexane (5.91 ml) at 0° C., and the mixture is stirred at the same temperature for 30 minutes. The solution is cooled to −78° C., and thereto is added gradually and dropwise a solution of (Z)-4-(3-chloro-4,5-dimethoxyphenyl)-4-methyl-3-methoxycarbonyl-3-butenoic acid methoxymethyl ester (2.94 g) in tetrahydrofuran (20 ml), and the mixture is further stirred at the same temperature for 30 minutes. The reaction mixture is cooled to −90° C., and thereto is added gradually and dropwise a solution of isonictinaldehyde (1.01 g) in tetrahydrofuran (10 ml), and the mixture is stirred at −90° C. for 20 minutes. To the reaction mixture is added a saturated aqueous ammonium chloride solution, and the mixture is extracted with ethyl acetate. The organic layer is washed, dried, and concentrated under reduced pressure to remove the solvent to give (Z)-4-(3-chloro-4,5-dimethoxyphenyl)-4-methyl-3-methoxycarbonyl-2-(4-pyridylhydroxymethyl)-3-butenoic acid methoxymethyl ester.
COCOC(=O)C(/C(C(=O)OC)=C(\C)c1cc(Cl)c(OC)c(OC)c1)C(O)c1ccncc1
null
COCOC(=O)C/C(C(=O)OC)=C(\C)c1cc(Cl)c(OC)c(OC)c1
C1CCOC1
CC(C)NC(C)C
[CH:1]([NH:4][CH:5]([CH3:7])C)([CH3:3])C.C([Li])CCC.[CH3:13][O:14][CH2:15][O:16][C:17](=[O:37])[CH2:18]/[C:19](/[C:33]([O:35][CH3:36])=[O:34])=[C:20](/[C:22]1[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][CH3:31])=[C:24]([Cl:32])[CH:23]=1)\[CH3:21].[Cl-].[NH4+].[O:40]1CC[CH2:42][CH2:41]1>CCCCCC>[CH3:13][O:14][CH2:15][O:16][C:17](=[O:37])[CH:18]([CH:41]([C:42]1[CH:3]=[CH:1][N:4]=[CH:5][CH:7]=1)[OH:40])/[C:19](/[C:33]([O:35][CH3:36])=[O:34])=[C:20](/[C:22]1[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][CH3:31])=[C:24]([Cl:32])[CH:23]=1)\[CH3:21]
null
CCCCCC
null
null
-78
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,406,545
C=O
null
null
null
ord_dataset-7456bda2326f4bebaa874a5474d4cc0d
2014-01-01T00:03:00
true
A mixture of (−)-3-(3,4-difluorophenyl)-3-methoxypyrrolidine (0.013 g, 0.061 mmol) in formic acid (1 ml) and formaldehyde (37% solution in water, 1 ml) was heated at 85° C. for 5 h. The solution was allowed to reach room temperature. The crude mixture was purified on a Biotage Isolute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1). The solvent was evaporated. The crude product analyzed by GCMS. Analysis showed 87% conversion. MS m/z (relative intensity, 70 eV) 227 (M+, 5), 212 (26), 197 (30), 141 (47), 57 (bp).
COC1(c2ccc(F)c(F)c2)CCN(C)C1
null
O=CO
COC1(c2ccc(F)c(F)c2)CCNC1
null
[F:1][C:2]1[CH:3]=[C:4]([C:9]2([O:14][CH3:15])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[CH:16](O)=O>C=O>[F:1][C:2]1[CH:3]=[C:4]([C:9]2([O:14][CH3:15])[CH2:13][CH2:12][N:11]([CH3:16])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8]
null
null
null
null
85
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,436,112
Cl
[Na+]
[OH-]
null
ord_dataset-275a3da8f45f4536ad29727f0ef9ba66
2014-01-01T00:06:00
true
To methyl 8-(4-(2-butoxyethoxy)phenyl)-1-(2-methyl-2-propen-1-yl)-1,2,3,4-tetrahydro-1-benzoazocine-5-carboxylate (1.65 g) were added tetrahydrofuran (45 ml) and methanol (45 ml), followed by adding an aqueous 1N sodium hydroxide solution (15 ml), and the mixture was stirred at 60° C. overnight. After cooling down to 0° C., water was added and the mixture was neutralized with 1N hydrochloric acid. After extracting with ethyl acetate, the organic layer was washed with saturated water and dried with magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was recrystallized from hexane-ethyl acetate to give 8-(4-(2-butoxyethoxy)phenyl)-1-(2-methyl-2-propen-1-yl)-1,2,3,4-tetrahydro-1-benzoazocine-5-carboxylic acid (0.97 g) as yellow crystals.
C=C(C)CN1CCCC(C(=O)O)=Cc2cc(-c3ccc(OCCOCCCC)cc3)ccc21
null
C=C(C)CN1CCCC(C(=O)OC)=Cc2cc(-c3ccc(OCCOCCCC)cc3)ccc21
null
null
[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:25]([CH2:26][C:27]([CH3:29])=[CH2:28])[CH2:24][CH2:23][CH2:22][C:21]([C:30]([O:32]C)=[O:31])=[CH:20][C:19]=3[CH:34]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].O1CCCC1.[OH-].[Na+].Cl>O.CO>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:25]([CH2:26][C:27]([CH3:29])=[CH2:28])[CH2:24][CH2:23][CH2:22][C:21]([C:30]([OH:32])=[O:31])=[CH:20][C:19]=3[CH:34]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]
8
O
C1CCOC1
CO
60
null
60.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
314,704
null
null
null
null
ord_dataset-bd998d3fe946475e835418aaf647c00d
1995-01-01T00:08:00
true
By the method described in Example 5, the title compound of Example 4 (0.5 g, 1.5 mmol) in 20 mL of CH2Cl2 was converted to its mixed anhydride with NMM (0.16 mL, 1.5 mmol) and IBCF (0.2 mL, 1.5 mmol). This intermediate was condensed with 4-aminopyridine (0.21 g, 2.25 mmol) to produce the title compound (94 mg).
O=C(CNC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21)Nc1ccncc1
null
O=C(O)CNC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21
Nc1ccncc1
null
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]2[O:6][C:7]3[CH:21]=[CH:20][CH:19]=[CH:18][C:8]=3[CH2:9][N:10]([C:11]([NH:13][CH2:14][C:15]([OH:17])=O)=[O:12])[C:4]=2[CH:3]=1.CN1CCOCC1.[NH2:31][C:32]1[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=1>C(Cl)Cl>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]2[O:6][C:7]3[CH:21]=[CH:20][CH:19]=[CH:18][C:8]=3[CH2:9][N:10]([C:11]([NH:13][CH2:14][C:15]([NH:31][C:32]3[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=3)=[O:17])=[O:12])[C:4]=2[CH:3]=1
null
CN1CCOCC1
ClCCl
null
null
15.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
602,589
null
null
null
null
ord_dataset-82e842e611ef4a05b6e7f9ea0a46d52d
2003-01-01T00:07:00
true
To a stirred, cold (0° C.) solution of (2R,4R)-1-[3-(4-fluorophenoxy)-propane-1-sulfonyl]-piperidine-2,4-dicarboxylic acid 2-tert-butyl ester 4-methyl ester (1.15 g, 2.5 mmol) in 10 mL of methylene chloride was added 10 mL of trifluoracetic acid. The mixture was allowed warm to ambient temperature (22° C.) over 16 hours. The mixture was concentrated in vacuo to give 970 mg of crude (2R,4R)-1-[3-(4-fluorophenoxy)-propane-1-sulfonyl]-piperidine-2,4-dicarboxylic acid 4-methyl ester as a orange solid.
COC(=O)[C@@H]1CCN(S(=O)(=O)CCCOc2ccc(F)cc2)[C@@H](C(=O)O)C1
null
COC(=O)[C@@H]1CCN(S(=O)(=O)CCCOc2ccc(F)cc2)[C@@H](C(=O)OC(C)(C)C)C1
null
null
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:10][CH2:9][N:8]([S:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)(=[O:13])=[O:12])[C@@H:7]([C:25]([O:27]C(C)(C)C)=[O:26])[CH2:6]1)=[O:4].FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:10][CH2:9][N:8]([S:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)(=[O:13])=[O:12])[C@@H:7]([C:25]([OH:27])=[O:26])[CH2:6]1)=[O:4]
null
ClCCl
O=C(O)C(F)(F)F
null
22
96.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,145,242
CC(C)(C)[O-]
[K+]
null
null
ord_dataset-68715347640045adb1b09e6a04722b0e
2012-01-01T00:03:00
true
4-[2-(2,4-Dichloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1H-pyridin-2-one (Example 119, 100 mg) was dissolved in THF (10 mL), and treated with t-BuOK (34 mg). After 5 minutes stirring, bromo-acetic acid methyl ester (0.03 mL) was added and the reaction mixture was stirred at 55° C. for 17 h. The reaction mixture was then cooled down to r.t., poured into water (50 mL) and extracted twice with ethyl acetate. The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (10 g silica gel, ethyl acetate/heptane 30:70) to give the title compound as colorless waxy solid (49 mg). MS (m/e)=438.1 (MH+).
COC(=O)Cn1ccc(C(O)(C(C)c2ccc(Cl)cc2Cl)C(F)(F)F)cc1=O
null
CC(c1ccc(Cl)cc1Cl)C(O)(c1cc[nH]c(=O)c1)C(F)(F)F
COC(=O)CBr
null
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]([CH3:23])[C:10]([C:16]1[CH:21]=[CH:20][NH:19][C:18](=[O:22])[CH:17]=1)([OH:15])[C:11]([F:14])([F:13])[F:12].CC([O-])(C)C.[K+].[CH3:30][O:31][C:32](=[O:35])[CH2:33]Br.O>C1COCC1>[CH3:30][O:31][C:32](=[O:35])[CH2:33][N:19]1[CH:20]=[CH:21][C:16]([C:10]([OH:15])([C:11]([F:14])([F:13])[F:12])[CH:9]([C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])[CH3:23])=[CH:17][C:18]1=[O:22]
0.08
C1CCOC1
O
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
589,959
null
null
null
null
ord_dataset-7a74d48eeefd45aba53e7258f3ae067a
2003-01-01T00:04:00
true
The title compound was prepared from {5-(methyl-propyl-amino)-2-[3-oxo-3-(3-[1,2,3]-triazol-1-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M118) (0.33 g, 0.59 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (115 mg, 44%).
CCCN(C)c1cc2c(cc1C(F)(F)F)NC(=O)CC(c1cccc(-n3ccnn3)c1)=N2
null
CCCN(C)c1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-n3ccnn3)c2)cc1C(F)(F)F
null
null
C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH3:18])[CH2:15][CH2:16][CH3:17])[C:11]([C:19]([F:22])([F:21])[F:20])=[CH:10][C:9]=1[NH:23][C:24](=[O:39])[CH2:25][C:26](=O)[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([N:33]2[CH:37]=[CH:36][N:35]=[N:34]2)[CH:28]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:18][N:14]([CH2:15][CH2:16][CH3:17])[C:12]1[C:11]([C:19]([F:20])([F:22])[F:21])=[CH:10][C:9]2[NH:23][C:24](=[O:39])[CH2:25][C:26]([C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([N:33]4[CH:37]=[CH:36][N:35]=[N:34]4)[CH:28]=3)=[N:7][C:8]=2[CH:13]=1
null
ClCCl
O=C(O)C(F)(F)F
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,620,166
[BH4-]
[Na+]
null
null
ord_dataset-35c51552812941cda45194a013d34bb9
2015-01-01T00:08:00
true
A solution of ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-4-formyl-3-methylnaphthalen-2-yl)acetate (6.0 mg, 14 μmol), NaBH4 (1.5 mg, 40 μmol), THF (250 μL), and EtOH (absolute, 500 μL) was stirred at 23° C. for 1 h. H2O (500 μL) and LiOH monohydrate (50 mg, 1.18 mmol) were added. The reaction was sealed and heated to 100° C. After 2 h, the reaction cooled to 23° C., filtered through a 0.45 micron filter, and directly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA). The product-containing fractions were combined and lyophilized, giving the title compound (parent form) (2.6 mg, 43%). 1H NMR (400 MHz, DMSO-d6) δ 12.76 (s, 1H), 8.27 (d, J=8.6 Hz, 1H), 7.72-7.65 (m, 2H), 7.58-7.48 (m, 2H), 7.39-7.33 (m, 2H), 7.18 (d, J=8.6 Hz, 1H), 5.07 (s, 1H), 5.01 (d, broad, J=2.7 Hz, 2H), 2.62 (s, 3H), 0.94 (s, 9H).
Cc1c(C(OC(C)(C)C)C(=O)O)c(-c2ccc(Cl)cc2)c2ccccc2c1CO
null
CCOC(=O)C(OC(C)(C)C)c1c(C)c(C=O)c2ccccc2c1-c1ccc(Cl)cc1
null
null
[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[C:20]([CH:23]=[O:24])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].C1COCC1.CCO>O>[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[C:20]([CH2:23][OH:24])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[C:25]1[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]
2
C1CCOC1
CCO
O
100
45
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
760,260
null
null
null
null
ord_dataset-2e58cb8db2bf482bbea23283b7e04488
2007-01-01T00:03:00
true
A thiourea such as N-[4-(isopropylformylamino)cyclohexyl]-methylthiourea (0.029 mmol, 1 equivalent), a bromoketone (0.044 mmol, 1.5 equivalent) and 2 equivalents of diisopropylethyl amine in 10 ml of EtOH were heated at reflux temperature for 2 days. The reaction mixture was concentrated in vacuo and the crude product chromatographed (silica) to obtain the desired product. This procedure was used to prepare examples 101–102.
CC(C)C(=O)NC1CCC(CNC(N)=S)CC1
null
CC(C)C(=O)NC1CCC(N(C)C(N)=S)CC1
NC(N)=S
O=C(Br)Br
[NH2:1][C:2]([NH2:4])=[S:3].[CH:5]([C:8]([NH:10][CH:11]1[CH2:16][CH2:15][CH:14](N(C)C(N)=S)[CH2:13][CH2:12]1)=[O:9])([CH3:7])[CH3:6].Br[C:23](Br)=O.C(N(C(C)C)CC)(C)C>CCO>[CH:5]([C:8]([NH:10][CH:11]1[CH2:16][CH2:15][CH:14]([CH2:23][NH:1][C:2]([NH2:4])=[S:3])[CH2:13][CH2:12]1)=[O:9])([CH3:7])[CH3:6]
null
CCN(C(C)C)C(C)C
CCO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,493,961
CCOC(=O)/N=N/C(=O)OCC
c1ccc(P(c2ccccc2)c2ccccc2)cc1
null
null
ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2
2014-01-01T00:10:00
true
To a round-bottomed flask was added methyl 2-(5-hydroxypyridin-2-yl)thiazole-5-carboxylate (400 mg), (S)-3-hydroxy-pyrrolidin-2-one (188 mg), PPh3 (443 mg), and THF (10 mL). DEAD (299 mg) was added dropwise at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 12 hours. After being diluted with ethyl acetate (50 mL), the organic layer was washed with water (20 mL×2) and brine (10 mL) and dried over anhydrous Na2SO4. After filtration and evaporation of the solvent, the residue obtained was purified by silica gel column chromatography eluting with petroleum ether/ethyl acetate (4:1 to 1:3) to afford the subtitle compound. MS ESI+: m/z=320 [M-FH]+.
COC(=O)c1cnc(-c2ccc(O[C@@H]3CCNC3=O)cn2)s1
null
O=C1NCC[C@@H]1O
COC(=O)c1cnc(-c2ccc(O)cn2)s1
null
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:9][C:10]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][N:12]=2)=[N:6][CH:7]=1.O[C@H:18]1[CH2:22][CH2:21][NH:20][C:19]1=[O:23].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C(OCC)(=O)C.C1COCC1>[O:23]=[C:19]1[C@H:18]([O:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[S:9][C:10]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][N:12]=3)=[N:6][CH:7]=2)[CH2:22][CH2:21][NH:20]1
12
C1CCOC1
CCOC(C)=O
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
219,838
N
[H-]
[Na+]
null
ord_dataset-6cb04513a4a244c0b612b566096f4b3d
1990-01-01T00:12:00
true
5-[1-(dimethylamino)-ethylideneamino]-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-imidazole-4-carbonitrile is reacted with sodium hydride in dioxane as described in Example 10 and the crude product is reacted with methanolic ammonia at room temperature over 18 hours. The mixture is concentrated to dryness and purified by silica gel chromatography to afford 7-amino-3-β-D-ribofuranosyl-N,N-dimethyl-3H-imidazo[4,5-b]pyridine-5-amine.
CN(C)c1cc(N)c2ncn([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c2n1
null
CC(=O)OC[C@H]1O[C@@H](n2cnc(C#N)c2N=C(C)N(C)C)[C@H](OC(C)=O)[C@@H]1OC(C)=O
null
null
[CH3:1][N:2]([CH3:31])[C:3](=[N:5][C:6]1[N:10]([C@@H:11]2[O:23][C@H:22]([CH2:24][O:25]C(=O)C)[C@@H:17]([O:18]C(=O)C)[C@H:12]2[O:13]C(=O)C)[CH:9]=[N:8][C:7]=1[C:29]#[N:30])[CH3:4].[H-].[Na+].N>O1CCOCC1>[NH2:30][C:29]1[CH:4]=[C:3]([N:2]([CH3:31])[CH3:1])[N:5]=[C:6]2[N:10]([C@@H:11]3[O:23][C@H:22]([CH2:24][OH:25])[C@@H:17]([OH:18])[C@H:12]3[OH:13])[CH:9]=[N:8][C:7]=12
null
C1COCCO1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,283,604
null
null
null
null
ord_dataset-d5c54236ecd94d61aaa071461bcfc426
2013-01-01T00:04:00
true
4-Chloro-2-methylquinoline-8-sulfonic dimethylamide (80 mg, 0.281 mmole) and 3,4-dichlorobenzylamine (100 mg, 0.568 mmole) were stirred at 155° C. for 10 min in a microwave oven. Methanol was added and the mixture was concentrated, mixed with dichloromethane and then filtered. The residue was purified using silica gel chromatography, eluting with dichloromethane:methanol 95:5. Precipitation in ethyl acetate gave a pink solid (15 mg, 13%).
Cc1cc(NCc2ccc(Cl)c(Cl)c2)c2cccc(S(=O)(=O)N(C)C)c2n1
null
NCc1ccc(Cl)c(Cl)c1
Cc1cc(Cl)c2cccc(S(=O)(=O)N(C)C)c2n1
null
[CH3:1][N:2]([CH3:18])[S:3]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:15]=1[N:14]=[C:13]([CH3:16])[CH:12]=[C:11]2Cl)(=[O:5])=[O:4].[Cl:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=1[Cl:28])[CH2:23][NH2:24]>CO>[CH3:1][N:2]([CH3:18])[S:3]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:15]=1[N:14]=[C:13]([CH3:16])[CH:12]=[C:11]2[NH:24][CH2:23][C:22]1[CH:25]=[CH:26][C:27]([Cl:28])=[C:20]([Cl:19])[CH:21]=1)(=[O:5])=[O:4]
null
CO
null
null
null
12.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,607,224
null
null
null
null
ord_dataset-9cecb3a8d3b9494191b28dcefea66af2
2015-01-01T00:07:00
true
The title compound was prepared in a manner similar to that described in Example 448 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-pyrazin-2-amine and racemic tert-butyl (1-((2-bromophenyl)sulfonyl)piperidin-3-yl)carbamate. MS (ESI): mass calcd. for C26H30FN5O4S, 527.20; m/z found, 528.3 [M+H]+. 1H NMR (400 MHz, CD3OD) δ 8.34 (d, J=9.1, 2H), 8.10-8.07 (m, 1H), 8.00 (m, 1H), 7.73-7.68 (m, 1H), 7.64-7.59 (m, 1H), 7.44-7.40 (m, 1H), 7.35-7.29 (m, 2H), 3.30-3.20 (m, 2H), 3.15-3.06 (m, 1H), 2.51-2.40 (m, 1H), 2.30-2.21 (m, 1H), 1.79-1.70 (m, 1H), 1.65-1.56 (m, 1H), 1.39-1.28 (m, 10H), 1.26-1.14 (m, 1H).
CC(C)(C)OC(=O)NC1CCCN(S(=O)(=O)c2ccccc2-c2ccc(-c3cnc(N)cn3)c(F)c2)C1
null
CC(C)(C)OC(=O)NC1CCCN(S(=O)(=O)c2ccccc2Br)C1
CC1(C)OB(c2ccc(-c3cnc(N)cn3)c(F)c2)OC1(C)C
null
[F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[CH:19][C:20]([NH2:23])=[N:21][CH:22]=1.Br[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[S:31]([N:34]1[CH2:39][CH2:38][CH2:37][CH:36]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:35]1)(=[O:33])=[O:32]>>[NH2:23][C:20]1[N:21]=[CH:22][C:17]([C:3]2[CH:4]=[CH:5][C:6]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[S:31]([N:34]3[CH2:39][CH2:38][CH2:37][CH:36]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:45])([CH3:44])[CH3:46])[CH2:35]3)(=[O:32])=[O:33])=[CH:7][C:2]=2[F:1])=[N:18][CH:19]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
435,581
Cl
[Li+]
[OH-]
null
ord_dataset-386da077ab2340638cada986e2ef0770
1999-01-01T00:07:00
true
A solution of 20 g of 4-[N'-methyl-N'-(3,5-bistrifluoromethyl-benzoyl)-amino]-5-(4-chlorophenyl)-pent-2-enoic acid ethyl ester and 15 g of lithium hydroxide monohydrate in 100 ml of THF/methanol/water 3:3:1 is stirred at room temperature for 4 hours, and then 200 ml of water and 1N hydrochloric acid are added (pH value approx. 2). The mixture is extracted twice with ethyl acetate. The combined organic phases are washed with water and saturated NaCl solution, dried (magnesium sulfate) and concentrated by evaporation. The title compound is obtained in the form of a colourless oil which can be used further without being further purified.
CN(C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(C=CC(=O)O)Cc1ccc(Cl)cc1
null
CCOC(=O)C=CC(Cc1ccc(Cl)cc1)N(C)C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
null
null
C([O:3][C:4](=[O:34])[CH:5]=[CH:6][CH:7]([N:16]([CH3:33])[C:17](=[O:32])[C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=1)C.O.[OH-].[Li+].O.Cl>C1COCC1.CO.O>[CH3:33][N:16]([CH:7]([CH2:8][C:9]1[CH:10]=[CH:11][C:12]([Cl:15])=[CH:13][CH:14]=1)[CH:6]=[CH:5][C:4]([OH:34])=[O:3])[C:17](=[O:32])[C:18]1[CH:19]=[C:20]([C:28]([F:29])([F:30])[F:31])[CH:21]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:23]=1
null
O
C1CCOC1
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
492,442
null
null
null
null
ord_dataset-3f9174c7efcb4f31becbd3516cde9572
2001-01-01T00:02:00
true
By the same reaction and treatment as in Example 48 using cycloheptanone oxime and ethyl 4-(4-(4-chloro-3-trifluoromethylphenyl)piperidin-1-yl)-n-butyrate, 3-(3-(4-(4-chloro-3-trifluoromethylphenyl)piperidin-1-yl)propyl)-5,6,7,8-tetrahydro-4H-cyclohepta[c]isoxazole is obtained.
FC(F)(F)c1cc(C2CCN(CCCc3onc4c3CCCCC4)CC2)ccc1Cl
null
ON=C1CCCCCC1
CCOC(=O)CCCN1CCC(c2ccc(Cl)c(C(F)(F)F)c2)CC1
null
[C:1]1(=[N:8][OH:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][CH2:25][C:26](OCC)=O)[CH2:19][CH2:18]2)=[CH:13][C:12]=1[C:31]([F:34])([F:33])[F:32]>>[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][CH2:25][C:26]3[O:9][N:8]=[C:1]4[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][C:2]=34)[CH2:19][CH2:18]2)=[CH:13][C:12]=1[C:31]([F:34])([F:32])[F:33]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
781,124
Cl
null
null
null
ord_dataset-8034115bd2ec4d3e95bd3ff7cfde0bde
2007-01-01T00:07:00
true
A mixture of 6-(1-(tert-butyloxycarbonyl)piperidin-4-yloxy)-4H-benzo[1,4]oxazin-3-one (3.78 g, 10.9 mmol), ethereal hydrogen chloride (50 mL) and dichloromethane (20 mL) was heated at 40° C. for 2 h, then allowed to stir at 20° C. for 18 h. The resulting colourless solid was collected by filtration to give the title compound (2.72 g, 88%).
O=C1COc2ccc(OC3CCNCC3)cc2N1
null
CC(C)(C)OC(=O)N1CCC(Oc2ccc3c(c2)NC(=O)CO3)CC1
null
null
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:16]=[CH:17][C:18]3[O:23][CH2:22][C:21](=[O:24])[NH:20][C:19]=3[CH:25]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:26]>ClCCl>[ClH:26].[NH:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15]2[CH:16]=[CH:17][C:18]3[O:23][CH2:22][C:21](=[O:24])[NH:20][C:19]=3[CH:25]=2)[CH2:12][CH2:13]1
18
ClCCl
null
null
40
null
88
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,432,519
null
null
null
null
ord_dataset-5e6956e6e8c24a168866a253f4a66c6c
2014-01-01T00:05:00
true
N-(2-(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenamidoethyl)-2′,4′-difluoro-4-hydroxybiphenyl-3-carboxamide was prepared in a similar fashion as N-(2-(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenamidoethyl)-2-hydroxybenzamide, using the appropriate 2′,4′-difluoro-4-hydroxybiphenyl-3-carboxylic acid starting material. Mass calculated for C37H44F2N2O3=602.75. found: [M+H]+=603.3.
CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCC(=O)NCCNC(=O)c1cc(-c2ccc(F)cc2F)ccc1O
null
CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCC(=O)NCCNC(=O)c1ccccc1O
O=C(O)c1cc(-c2ccc(F)cc2F)ccc1O
null
[C:1]([NH:24][CH2:25][CH2:26][NH:27][C:28](=[O:36])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[OH:35])(=[O:23])[CH2:2][CH2:3]/[CH:4]=[CH:5]\[CH2:6]/[CH:7]=[CH:8]\[CH2:9]/[CH:10]=[CH:11]\[CH2:12]/[CH:13]=[CH:14]\[CH2:15]/[CH:16]=[CH:17]\[CH2:18]/[CH:19]=[CH:20]\[CH2:21][CH3:22].[F:37][C:38]1[CH:43]=[C:42]([F:44])[CH:41]=[CH:40][C:39]=1C1C=CC(O)=C(C(O)=O)C=1>>[C:1]([NH:24][CH2:25][CH2:26][NH:27][C:28]([C:29]1[CH:34]=[C:33]([C:41]2[CH:40]=[CH:39][C:38]([F:37])=[CH:43][C:42]=2[F:44])[CH:32]=[CH:31][C:30]=1[OH:35])=[O:36])(=[O:23])[CH2:2][CH2:3]/[CH:4]=[CH:5]\[CH2:6]/[CH:7]=[CH:8]\[CH2:9]/[CH:10]=[CH:11]\[CH2:12]/[CH:13]=[CH:14]\[CH2:15]/[CH:16]=[CH:17]\[CH2:18]/[CH:19]=[CH:20]\[CH2:21][CH3:22]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
700,325
OP(O)O
[I-]
[K+]
null
ord_dataset-bbd7e53f000345838ad4920a07a169ff
2006-01-01T00:03:00
true
To a solution of hydroxy(1-acetyl-4,6-dimethylindolin-5-yl)acetic acid obtained in Example 1 (280 g) in acetic acid (1120 ml) were added phosphorous acid (130 g) and potassium iodide (17.6 g), and the resulting mixture was stirred for 2 hours at 100–107° C. After cooling to 50° C., water (1120 ml) was added, and crystals precipitated were separated by filtration and dried to afford (1-acetyl-4,6-dimethylindolin-5-yl)acetic acid (223 g, yield: 85%).
CC(=O)N1CCc2c1cc(C)c(CC(=O)O)c2C
null
CC(=O)N1CCc2c1cc(C)c(C(O)C(=O)O)c2C
null
null
O[CH:2]([C:6]1[C:7]([CH3:19])=[C:8]2[C:12](=[CH:13][C:14]=1[CH3:15])[N:11]([C:16](=[O:18])[CH3:17])[CH2:10][CH2:9]2)[C:3]([OH:5])=[O:4].P(O)(O)O.[I-].[K+].O>C(O)(=O)C>[C:16]([N:11]1[C:12]2[C:8](=[C:7]([CH3:19])[C:6]([CH2:2][C:3]([OH:5])=[O:4])=[C:14]([CH3:15])[CH:13]=2)[CH2:9][CH2:10]1)(=[O:18])[CH3:17]
2
CC(=O)O
O
null
50
84.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
274,531
null
null
null
null
ord_dataset-ee287d49cb8642e59ae9c3951f746312
1993-01-01T00:08:00
true
A solution of [3-[[2-(diethoxyphosphinyl)ethyl]amino]propyl]carbamic acid phenylmethyl ester (3.17 g, 8.5 mmol) in absolute ethanol (40 mL) was added over 45 minutes to 3,4-diethoxy-3-cyclobutene-1,2-dione (2.3 mL, 16 mmol) dissolved ethanol (55 mL). After leaving overnight, the reaction mixture was preadsorbed onto silica gel and purified by flash chromotography (7 cm diameter, gradient elution was 2.5-10% methanol in dichloromethane) to yield [3-[[2-(diethoxyphosphinyl)ethyl](2-ethoxy-3,4-dioxo-1-cyclobuten-1-yl)amino]propyl]carbamic acid phenylmethyl ester as a viscous oil (3.75 g, 89%); 1H NMR (CDCl3, 400 MHz): δ 7.35 (m, 5H), 5.45 (br m, NH), 5.09 (s, 2H), 4.80-4.71 (m, 2H), 4.16-4.09 (m, 4H), 3.90-3.48 (m, 4H), 3.23-3.20 (m, 2H), 2.16-2.05 (m, 2 H), 1.85-1.79 (m, 2H), 1.47, 1.41 (t, J=7 Hz, 3H), 1.34 (t, J=7 Hz, 6H).
CCOc1c(N(CCCNC(=O)OCc2ccccc2)CCP(=O)(OCC)OCC)c(=O)c1=O
null
CCOc1c(OCC)c(=O)c1=O
CCOP(=O)(CCNCCCNC(=O)OCc1ccccc1)OCC
null
[C:1]1([CH2:7][O:8][C:9](=[O:25])[NH:10][CH2:11][CH2:12][CH2:13][NH:14][CH2:15][CH2:16][P:17]([O:22][CH2:23][CH3:24])([O:19][CH2:20][CH3:21])=[O:18])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:26]([O:28][C:29]1[C:30](=O)[C:31](=[O:36])[C:32]=1[O:33]CC)[CH3:27]>C(O)C>[C:1]1([CH2:7][O:8][C:9](=[O:25])[NH:10][CH2:11][CH2:12][CH2:13][N:14]([CH2:15][CH2:16][P:17]([O:19][CH2:20][CH3:21])([O:22][CH2:23][CH3:24])=[O:18])[C:30]2[C:31](=[O:36])[C:32](=[O:33])[C:29]=2[O:28][CH2:26][CH3:27])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
null
CCO
null
null
null
null
88.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
769,727
Cl
null
null
null
ord_dataset-8214eb8444a44dc2900ccb42dbeff15e
2007-01-01T00:05:00
true
By using a method similar to the method of Example 532, combine 2-(2-nitro-phenylamino)-benzo[b]thiophene-3-carbonitrile (5.0 g, 17.0 mmol) and Tin(II) chloride (9.65 g, 51.0 mmol) in a mixed solvent of EtOH (50 mL) and 5.0 N HCl (50 mL), heat the suspension to reflux for 3 hours, cool to RT. The title compound 4.65 g (yield 91%) is obtained as a yellow solid by suction filtration. Mass spectrum: ACPI (m/e): 266.0 ((M+1-HCl); 1H NMR (300 MHz, DMSO-d6) ppm: 11.7 (br, 1H), 10.00 (br, 1H), 9.10 (br, 2H), 7.90–7.85 (m, 1H), 7.72–7.65 (m, 1H), 7.48–7.38 (m, 1H), 7.35–7.28 (m, 1H), 7.22–6.98 (m, 4H).
NC1=Nc2ccccc2Nc2sc3ccccc3c21
null
N#Cc1c(Nc2ccccc2[N+](=O)[O-])sc2ccccc12
Cl[Sn]Cl
null
[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C:11]1[S:15][C:14]2[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=2[C:12]=1[C:20]#[N:21])([O-])=O.[Sn](Cl)[Cl:23].Cl>CCO>[ClH:23].[CH:16]1[C:14]2[S:15][C:11]3[NH:10][C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=4[N:1]=[C:20]([NH2:21])[C:12]=3[C:13]=2[CH:19]=[CH:18][CH:17]=1
null
CCO
null
null
25
null
90.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
311,996
null
null
null
null
ord_dataset-04982f13ed08448d93df6794846500f3
1995-01-01T00:06:00
true
In 30.0 ml of tetrahydrofuran (THF), 10.0 g (45.42 mmol) of 2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)fluoromethoxyiminoacetic acid were stirred at room temperature to completely dissolve the latter in the former, followed by cooling to -12° C. Added dropwise to the reaction mixture was a chlorinating reagent, which had been prepared beforehand by gradually adding 7.65 g (49.89 mmol) of phosphorus oxychloride at 5° C. into a mixture of 20 ml of THF and 3.7 g (49.93 mmol) of N,N-dimethylformamide (DMF) and then reacting them for 30 minutes. Subsequent to their reaction for 60 minutes with the temperature maintained at -15° C., the reaction mixture was poured into 150 ml of ice water and was then stirred for 20 minutes to precipitate crystals. The crystals were collected by filtration, washed twice with 15 ml aliquots of ice water and then, under reduced pressure, dried, whereby the title compound was obtained. Yield: 8.50 g (77.9%). Purity: 95.7%.
Nc1nc(/C(=N/OCF)C(=O)Cl)ns1
null
O=P(Cl)(Cl)Cl
Nc1nc(/C(=N/OCF)C(=O)O)ns1
null
[NH2:1][C:2]1[S:6][N:5]=[C:4](/[C:7](=[N:11]/[O:12][CH2:13][F:14])/[C:8](O)=[O:9])[N:3]=1.P(Cl)(Cl)([Cl:17])=O.CN(C)C=O>O1CCCC1>[NH2:1][C:2]1[S:6][N:5]=[C:4](/[C:7](=[N:11]/[O:12][CH2:13][F:14])/[C:8]([Cl:17])=[O:9])[N:3]=1
0.33
CN(C)C=O
C1CCOC1
null
-12
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
382,289
null
null
null
null
ord_dataset-f367d8d2baac490b9204609a79420961
1997-01-01T00:11:00
true
In an oven-dried round bottomed flask was added L-proline, 1-[2-(3,4,5-trimethoxyphenyl)-2-oxoethyl] 2-(4-aminophenyl)ethylamide (100 mg, 0.23 mmol), and tetrahydrofuran (5 mL). The solution was stirred at 22° C., and treated with pyridine (0.037 mL, 0.45 mmol, 2.0 eq) followed by acetyl chloride (0.024 mL, 0.34 mmol, 1.5 eq). The reaction mixture was allowed to stir for one hour. The solvent was removed in vacuo and the residue partitioned between EtOAc (50 mL) and sat. NaHCO3 (50 mL). The organic layer was washed with sat. aq. NaCl, dried (MgSO4) and concentrated to an oil. The oil was purified by flash chromatography to provide 70 mg of L-proline, 1-[2-(3,4,5-trimethoxyphenyl)-2-oxoethyl] 2-(4-(N-acetyl)aminophenyl)ethylamide as a foam.
COc1cc(C(=O)CC(Cc2ccc(NC(C)=O)cc2)NC(=O)[C@@H]2CCCN2)cc(OC)c1OC
null
COc1cc(C(=O)CC(Cc2ccc(N)cc2)NC(=O)[C@@H]2CCCN2)cc(OC)c1OC
CC(=O)Cl
null
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13](=[O:32])[CH2:14][CH:15]([NH:24][C:25](=[O:31])[C@@H:26]2[CH2:30][CH2:29][CH2:28][NH:27]2)[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].N1C=CC=CC=1.[C:39](Cl)(=[O:41])[CH3:40]>O1CCCC1>[CH3:12][O:11][C:7]1[CH:6]=[C:5]([C:13](=[O:32])[CH2:14][CH:15]([NH:24][C:25](=[O:31])[C@@H:26]2[CH2:30][CH2:29][CH2:28][NH:27]2)[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([NH:23][C:39](=[O:41])[CH3:40])=[CH:19][CH:18]=2)[CH:4]=[C:3]([O:2][CH3:1])[C:8]=1[O:9][CH3:10]
null
C1CCOC1
c1ccncc1
null
22
null
62.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
424,146
null
null
null
null
ord_dataset-1a231de00bfe4443b547e1f03885ed41
1999-01-01T00:01:00
true
2-(3-tert-Butoxycarbonylaminomethylpyrrolidin-1-yl)ethylamine (1 g) was dissolved in methylene chloride (10 ml) and a solution of methyl isocyanate (0.24 ml) in methylene chloride was dropwise added under ice-cooling. The mixture was stirred at room temperature for 1 hr, and the reaction mixture was concentrated under reduced pressure to give 1-(2-(3-methylureido)ethyl)-3-tert-butoxycarbonylaminomethylpyrrolidine.
CNC(=O)NCCN1CCC(CNC(=O)OC(C)(C)C)C1
null
CN=C=O
CC(C)(C)OC(=O)NCC1CCN(CCN)C1
null
[C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][NH2:17])[CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18][N:19]=[C:20]=[O:21]>C(Cl)Cl>[CH3:18][NH:19][C:20](=[O:21])[NH:17][CH2:16][CH2:15][N:12]1[CH2:13][CH2:14][CH:10]([CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:11]1
1
ClCCl
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
900,401
null
null
null
null
ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded
2009-01-01T00:08:00
true
The title compound was prepared from [4-(3-amino-phenyl)-8-chloro-quinolin-3-yl]-phenyl-methanone and (3-formyl-phenyl)-acetic acid methyl ester according to the procedure of Example 66. MS (ESI) m/z 507.
O=C(O)Cc1cccc(CNc2cccc(-c3c(C(=O)c4ccccc4)cnc4c(Cl)cccc34)c2)c1
null
Nc1cccc(-c2c(C(=O)c3ccccc3)cnc3c(Cl)cccc23)c1
COC(=O)Cc1cccc(C=O)c1
null
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[C:13]([Cl:18])[CH:14]=[CH:15][CH:16]=3)[N:11]=[CH:10][C:9]=2[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:20])[CH:5]=[CH:6][CH:7]=1.C[O:28][C:29](=[O:39])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH:37]=O)[CH:32]=1>>[C:19]([C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:8]=1[C:4]1[CH:3]=[C:2]([NH:1][CH2:37][C:33]3[CH:32]=[C:31]([CH2:30][C:29]([OH:39])=[O:28])[CH:36]=[CH:35][CH:34]=3)[CH:7]=[CH:6][CH:5]=1)=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:18])(=[O:20])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
691,665
[Na+]
[OH-]
null
null
ord_dataset-6214af00a7eb47f3887ef21a94320a7e
2005-01-01T00:11:00
true
Sodium hydroxide (1.2 g, 3.0 mmole) was added to a solution of 4-(1,2-dimethyl-imidazol-5-yl)-2-(4-acetamidoanilino)pyrimidine (Example 164; 1.25 g, 3.88 mmole) in isopropanol (12 mL) and water (0.5 mL) and the mixture heated under reflux for 90 minutes. The mixture was allowed to cool and was partitioned between saturated aqueous sodium hydrogen carbonate solution and EtOAc. The organic layer was separated and the volatiles evaporated. The residue was purified by column chromatography on silica gel eluting with DCM/7M methanolic ammonia (96:4) to give the title compound (0.75 g, 69%) as a brown solid. NMR: 2.33 (s, 3H), 3.85 (s, 3H), 4.75 (brs, 2H), 6.51 (d, 2H), 6.92 (d, 1H), 7.22 (d, 2H), 7.51 (s, 1H), 8.22 (d, 1H), 8.90 (s, 1H); m/z 281.
Cc1ncc(-c2ccnc(Nc3ccc(N)cc3)n2)n1C
null
CC(=O)Nc1ccc(Nc2nccc(-c3cnc(C)n3C)n2)cc1
null
null
[OH-].[Na+].[CH3:3][N:4]1[C:8]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22]C(=O)C)=[CH:18][CH:17]=3)[N:10]=2)=[CH:7][N:6]=[C:5]1[CH3:26]>C(O)(C)C.O>[CH3:3][N:4]1[C:8]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=3)[N:10]=2)=[CH:7][N:6]=[C:5]1[CH3:26]
null
CC(C)O
O
null
null
69
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,580,458
[Br-]
null
null
null
ord_dataset-380e279f82154dba9e08ab51b3bdd08a
2015-01-01T00:05:00
true
To a solution of 1-(3-bromophenyl)-5-[(4-methoxybenzyl)oxy]-4-oxo-1,4-dihydropyridine-2-carbaldehyde (3.0 g, 7.25 mmol), in dry THF (50 mL) was added MeMgBr (7.25 mL of a 3 M solution in THF, 21.8 mmol) dropwise at −30° C., and the reaction mixture was stirred at −30° C. then warmed to room temperature and stirred for another 2 h. The reaction mixture was cooled to 0° C., 2 mL water was added, and the mixture was diluted with ethyl acetate. The layers were separated, and the organic fraction was dried (MgSO4), concentrated under reduced pressure, and purified by Prep-HPLC to give 1.8 g (58%) of 1-(3-bromophenyl)-2-(1-hydroxyethyl)-5-[(4-methoxybenzyl)oxy]pyridin-4(1H)-one. Chiral resolution of 12.0 g 1-(3-bromophenyl)-2-(1-hydroxyethyl)-5-[(4-methoxybenzyl)oxy]pyridin-4(1H)-one was accomplished by SFC of racemic material using a Chiral Technologies ChiralPak AD-H column (25% MeOH in CO2, 3 cm diameter×25 cm length, 70 mL/min flow, 200 mg per injection), and afforded (80%) of the first eluting enantiomer and (79%) of the second eluting enantiomer. 1H-NMR (CD3OD, 400 MHz) δ 7.76 (d, J=8.0 Hz, 1H), 7.64 (s, 1H), 7.51-7.41(m, 2H), 7.38-7.35 (m, 2H), 7.33-7.31 (m, 2H), 6.88-6.86 (m, 2H), 6.76 (s, 1H), 4.95 (s, 2H), 4.39-4.34 (m, 1H), 3.76 (s, 3H), 1.26 (d, J=6.0 Hz, 2H). MS (ESI) m/z (M+H)+ 430.1/432.1.
COc1ccc(COc2cn(-c3cccc(Br)c3)c(C(C)O)cc2=O)cc1
null
COc1ccc(COc2cn(-c3cccc(Br)c3)c(C=O)cc2=O)cc1
C[Mg+]
null
[Br:1][C:2]1[CH:3]=[C:4]([N:8]2[CH:13]=[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:11](=[O:24])[CH:10]=[C:9]2[CH:25]=[O:26])[CH:5]=[CH:6][CH:7]=1.[CH3:27][Mg+].[Br-].O>C1COCC1.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([N:8]2[CH:13]=[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:11](=[O:24])[CH:10]=[C:9]2[CH:25]([OH:26])[CH3:27])[CH:5]=[CH:6][CH:7]=1
null
O
C1CCOC1
CCOC(C)=O
-30
58
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
330,938
[BH4-]
[Na+]
null
null
ord_dataset-2c460e2ef9934444aaf26fec1f75741f
1996-01-01T00:05:00
true
To a solution of 1-{4-[2-(2-methylphenyl)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one (620 mg) in methanol (20 ml) was added sodium borohydride (49.4 mg) and the mixture was stirred at ambient temperature for 4 hours. The mixture was diluted with chloroform and the solution was washed with water and brine, and dried over magnesium sulfate. The solvent was evaporated in vacuo to give a syrup and the residue was purified by silica gel column (30g, 1% methanol in chloroform) to give 5-hydroxy-1-{4-[2-(2-methylphenyl)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-1-benzazepine (580 mg).
Cc1ccccc1-c1ccccc1C(=O)Nc1ccc(C(=O)N2CCCC(O)c3ccccc32)cc1
null
Cc1ccccc1-c1ccccc1C(=O)Nc1ccc(C(=O)N2CCCC(=O)c3ccccc32)cc1
null
null
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:36]=[CH:35][CH:34]=[CH:33][C:9]=1[C:10]([NH:12][C:13]1[CH:32]=[CH:31][C:16]([C:17]([N:19]2[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[C:23](=[O:30])[CH2:22][CH2:21][CH2:20]2)=[O:18])=[CH:15][CH:14]=1)=[O:11].[BH4-].[Na+]>CO.C(Cl)(Cl)Cl>[OH:30][CH:23]1[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[N:19]([C:17](=[O:18])[C:16]2[CH:15]=[CH:14][C:13]([NH:12][C:10](=[O:11])[C:9]3[CH:33]=[CH:34][CH:35]=[CH:36][C:8]=3[C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[CH3:1])=[CH:32][CH:31]=2)[CH2:20][CH2:21][CH2:22]1
4
ClC(Cl)Cl
CO
null
25
null
93.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,578,869
[K+]
null
null
null
ord_dataset-9741bb5fd93044078df2a45f45733054
2015-01-01T00:04:00
true
15.0 g (124.4 mmol) of 2-methylbutyryl chloride were dissolved in 150 ml of abs. THF and cooled to 0° C., and 114 ml (114 mmol) of a 1 M solution of potassium tert-butylate in THF were added dropwise. After the addition had ended, the mixture was stirred at 0° C. for 1 h and then at RT for h, and about half of the solvent was then removed under reduced pressure. After addition of diethyl ether, sat. sodium bicarbonate solution was added dropwise with vigorous stirring. After phase separation, the aqueous phase was extracted with diethyl ether, and the combined organic phases were washed with sat. sodium carbonate solution, dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by vacuum distillation (19 mm Hg, 40-45° C.). This gave a total of 6.35 g of the target product (32.3% of theory).
CCC(C)C(=O)OC(C)(C)C
null
CC(C)(C)[O-]
CCC(C)C(=O)Cl
null
[CH3:1][CH:2]([CH2:6][CH3:7])[C:3](Cl)=[O:4].[CH3:8][C:9]([O-:12])([CH3:11])[CH3:10].[K+]>C1COCC1>[CH3:1][CH:2]([CH2:6][CH3:7])[C:3]([O:12][C:9]([CH3:11])([CH3:10])[CH3:8])=[O:4]
1
C1CCOC1
null
null
0
32.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
882,129
O=C([O-])[O-]
[K+]
null
null
ord_dataset-3592bd645cd143ee8274cd0d834ae581
2009-01-01T00:05:00
true
A mixture of 0.48 g of 3-acetoxy-2-(methoxycarbonyl)methylthiopyridine, 0.15 g of potassium carbonate, and 3 ml of methanol was stirred at room temperature for 3 hours. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography to give 0.26 g of 3-hydroxy-2-(methoxycarbonyl)methylthiopyridine.
COC(=O)CSc1ncccc1O
null
COC(=O)CSc1ncccc1OC(C)=O
null
null
C([O:4][C:5]1[C:6]([S:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])=[N:7][CH:8]=[CH:9][CH:10]=1)(=O)C.C(=O)([O-])[O-].[K+].[K+].CO>O>[OH:4][C:5]1[C:6]([S:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])=[N:7][CH:8]=[CH:9][CH:10]=1
3
CO
O
null
25
65.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,601,926
Cl
null
null
null
ord_dataset-e8c6a25568b64529b960953990e6921f
2015-01-01T00:06:00
true
4-((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(2-(6-(carboxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)ethylcarbamoyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yloxy)-2,2-dimethyl-4-oxobutanoic acid (Example 80, 0.3 g) was taken in MeOH (3 ml) and cooled the contents to 0° C. then Aq HCl (0.5 ml) was added and the contents were stirred for 6 hours at room temperature. After completion of the reaction (monitored by TLC), the reaction mixture was evaporated under reduced pressure. The residue was taken in water and extracted with DCM, the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 5% methanol in DCM as eluent to furnish the title compound (0.08 g) as a white solid. 1H NMR (300 MHz, CDCl3): 0.57-0.97 (m, 19H); 1.18-1.21 (m, 8H); 1.25-1.41 (m, 12H); 1.49-1.62 (m, 8H); 1.65-1.82 (m, 10H); 1.85-1.98 (m, 4H); 2.56-2.69 (m, 2H); 2.88-3.06 (m, 3H); 3.29-3.38 (m, 1H); 3.89-3.90 (m, 1H); 4.44-4.47 (m, 1H); 4.56 (s, 1H); 4.71 (s, 1H); Mass: 744 [M+1].
C=C(C)[C@@H]1CC[C@]2(C(=O)NCCC(O)CC(O)CC(=O)O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](OC(=O)CC(C)(C)C(=O)O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
null
C=C(C)[C@@H]1CC[C@]2(C(=O)NCCC3CC(CC(=O)OC(C)(C)C)OC(C)(C)O3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](OC(=O)CC(C)(C)C(=O)O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
null
null
C([O:5][C:6](=[O:60])[CH2:7][CH:8]1[O:13]C(C)(C)[O:11][CH:10]([CH2:16][CH2:17][NH:18][C:19]([C@:21]23[CH2:56][CH2:55][C@@H:54]([C:57]([CH3:59])=[CH2:58])[C@@H:22]2[C@@H:23]2[C@@:36]([CH3:39])([CH2:37][CH2:38]3)[C@@:35]3([CH3:40])[C@@H:26]([C@:27]4([CH3:53])[C@@H:32]([CH2:33][CH2:34]3)[C:31]([CH3:42])([CH3:41])[C@@H:30]([O:43][C:44](=[O:52])[CH2:45][C:46]([CH3:51])([CH3:50])[C:47]([OH:49])=[O:48])[CH2:29][CH2:28]4)[CH2:25][CH2:24]2)=[O:20])[CH2:9]1)(C)(C)C.Cl>CO>[C:47]([C:46]([CH3:51])([CH3:50])[CH2:45][C:44]([O:43][C@H:30]1[CH2:29][CH2:28][C@@:27]2([CH3:53])[C@@H:32]([CH2:33][CH2:34][C@:35]3([CH3:40])[C@@H:26]2[CH2:25][CH2:24][C@H:23]2[C@@:36]3([CH3:39])[CH2:37][CH2:38][C@@:21]3([C:19]([NH:18][CH2:17][CH2:16][CH:10]([OH:11])[CH2:9][CH:8]([OH:13])[CH2:7][C:6]([OH:60])=[O:5])=[O:20])[CH2:56][CH2:55][C@@H:54]([C:57]([CH3:59])=[CH2:58])[C@@H:22]32)[C:31]1([CH3:42])[CH3:41])=[O:52])([OH:49])=[O:48]
6
CO
null
null
0
null
30.1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
996,510
O=C([O-])[O-]
[Cs+]
null
null
ord_dataset-b6d8835b0c934476a36e6149e7597487
2010-01-01T00:09:00
true
To a solution of 6-Bromo-2-(2,4-dichloro-benzoyl)-benzofuran-3-one (3.30 g, 8.55 mmol) in acetone (50 mL) was added dimethyl sulfate (1.19 g, 9.40 mmol) and cesium carbonate (4.18 g, 12.82 mmol). The resulting mixture was heated at 50 deg for 6 hours is at which time the reaction mixture was concentrated via rotary evaporation. The resulting mixture was taken up in EtOAc and washed twice with water and one time with a saturated sodium carbonate solution. The organic portion was dried over MgSO4 and then filtered and concentrated. The resultant oil was purified via column chromatography (10% MeOH/Dichloromethane) to provide the title compound (950 mg, 28%). 1H-NMR (CDCl3): δ 8.03 (d, 1H), 7.65 (d, 1H), 7.46 (m, 2H), 7.35 (m, 2H), 2.46 (s, 3H).
COc1c(C(=O)c2ccc(Cl)cc2Cl)oc2cc(Br)ccc12
null
O=C(c1ccc(Cl)cc1Cl)C1Oc2cc(Br)ccc2C1=O
COS(=O)(=O)OC
null
[Br:1][C:2]1[CH:21]=[CH:20][C:5]2[C:6](=[O:19])[CH:7]([C:9](=[O:18])[C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=3[Cl:17])[O:8][C:4]=2[CH:3]=1.S(OC)(O[CH3:26])(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[Br:1][C:2]1[CH:21]=[CH:20][C:5]2[C:6]([O:19][CH3:26])=[C:7]([C:9]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=3[Cl:17])=[O:18])[O:8][C:4]=2[CH:3]=1
null
CC(C)=O
null
null
null
27.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,186,845
CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
F[P-](F)(F)(F)(F)F
null
null
ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff
2012-01-01T00:07:00
true
To a vial containing a solution of 2-(2,6-dichloro-phenyl)-3H-benzoimidazol-5-ylamine in dioxane (0.2 M, 0.10 mL) was added DIPEA (0.5 M in toluene, 0.050 mL) and acetic acid (0.2 M in toluene, 0.12 mL), followed by BOP reagent (0.2 M in DMF, 0.15 mL). After overnight at ambient temperature, the mixture was then diluted by MeOH and the whole was loaded onto a solid phase extraction (SPE) cartridge that contained strong cation exchange (SCX) (1 g media in 6 mL cartridge, United Chemical Technology). Wash-to-waste (5 mL MeOH) was followed by elute-to-collect (5 mL 20:2:1 ethyl acetate-MeOH-Et3N) and, after evaporation of volatiles, the crude was further purified by silica gel column chromatography to N-[2-(2-Chloro-phenyl)-3H-benzoimidazol-5-yl]-acetamide: MS (m/z) 320.02 (M+1).
CC(=O)Nc1ccc2nc(-c3ccccc3Cl)[nH]c2c1
null
Nc1ccc2nc(-c3c(Cl)cccc3Cl)[nH]c2c1
CC(=O)O
null
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[NH:10][C:11]2[CH:17]=[C:16]([NH2:18])[CH:15]=[CH:14][C:12]=2[N:13]=1.CCN(C(C)C)C(C)C.[C:28](O)(=[O:30])[CH3:29].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>O1CCOCC1.CO>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[CH:2][C:3]=1[C:9]1[NH:10][C:11]2[CH:17]=[C:16]([NH:18][C:28](=[O:30])[CH3:29])[CH:15]=[CH:14][C:12]=2[N:13]=1
8
CCN(C(C)C)C(C)C
CO
C1COCCO1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
422,390
null
null
null
null
ord_dataset-1a231de00bfe4443b547e1f03885ed41
1999-01-01T00:01:00
true
substituting 1-(2-(2,2,2-trifluoroethoxy)phenyl]piperazine and 1-biphenyl-3-ylmethyl-3-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione gave 1-biphenyl-3-ylmethyl-3-(3-{4-[2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl}-propyl)-5-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride, m.p. 93°-94° C.; Anal.: Calcd. for C33H35F3N4O3.HCl: C, 63.06; H, 5.77; N, 8.92%; Found: C, 61.66; H, 5.90; N, 8.50%;
Cc1cn(Cc2cccc(-c3ccccc3)c2)c(=O)n(CCCN2CCN(c3ccccc3OCC(F)(F)F)CC2)c1=O
Cl
FC(F)(F)COc1ccccc1N1CCNCC1
Cc1cn(Cc2cccc(-c3ccccc3)c2)c(=O)n(CCCCl)c1=O
null
[F:1][C:2]([F:18])([F:17])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.[C:19]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][N:26]2[CH:31]=[C:30]([CH3:32])[C:29](=[O:33])[N:28]([CH2:34][CH2:35][CH2:36][Cl:37])[C:27]2=[O:38])[CH:20]=1>>[ClH:37].[C:19]1([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][N:26]2[CH:31]=[C:30]([CH3:32])[C:29](=[O:33])[N:28]([CH2:34][CH2:35][CH2:36][N:14]3[CH2:15][CH2:16][N:11]([C:6]4[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=4[O:4][CH2:3][C:2]([F:1])([F:17])[F:18])[CH2:12][CH2:13]3)[C:27]2=[O:38])[CH:20]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
953,071
[H-]
[Na+]
null
null
ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8
2010-01-01T00:04:00
true
22.5 ml (113 mmol) of triethyl phosphono-acetate are dissolved in 100 ml of THF. 4.5 g (113 mmol) of 60% sodium hydride are then added, and the medium is stirred for 30 minutes at ambient temperature. A solution of 20 g (75.6 mmol) of 3-(tert-butyldimethylsilanyloxy)propan-1-one in 100 ml of THF is then added drop by drop. The medium is stirred for 6 hours, then treated with water and extracted with ethyl acetate. The residue obtained is purified by chromatography on silica gel (eluent ethyl acetate 10-heptane 90). A yellow oil is obtained (m=7.6 g; Y=30%).
CCOC(=O)/C=C(\CC)c1cccc(O[Si](C)(C)C(C)(C)C)c1
null
O
CC(C)(C)[Si](C)(C)OCCC=O
C1CCOC1
[H-].[Na+].[Si:3]([O:10][CH2:11][CH2:12][CH:13]=O)([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].[OH2:15].[CH2:16]1[CH2:20][O:19][CH2:18][CH2:17]1>>[Si:3]([O:10][C:11]1[CH:12]=[C:13](/[C:11](/[CH2:12][CH3:13])=[CH:17]/[C:18]([O:19][CH2:20][CH3:16])=[O:15])[CH:7]=[CH:6][CH:8]=1)([C:6]([CH3:7])([CH3:8])[CH3:9])([CH3:4])[CH3:5]
0.5
null
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
74,723
C[C@H]1CC(=O)C=C2CC[C@H]3[C@@H]4CC[C@H](O)[C@@]4(C)CC[C@@H]3[C@]21CO
null
null
null
ord_dataset-b9d8ddf9c2884d40859b6b5f24815a7d
1980-01-01T00:12:00
true
Substituting 17β,19-dihydroxy-1α,17α-dimethyl-4-androsten-3-one and 17β,19-dihydroxy-4-methyl-4-androsten-3-one in lieu of the 17β,19-dihydroxy-1α-methyl-4-androsten-3-one above, results in the preparation of 1α,17α-dimethyl-4-androstene-17β,19-diol and 4-methyl-4-androsten-17β,19-diol, respectively.
CC1=C2CC[C@@H]3[C@H](CC[C@]4(C)[C@@H](O)CC[C@@H]34)[C@@]2(CO)CCC1
null
CC1=C2CC[C@@H]3[C@H](CC[C@]4(C)[C@@H](O)CC[C@@H]34)[C@@]2(CO)CCC1=O
null
null
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]2[C@H:8]3[C@H:19]([CH2:20][CH2:21][C@:3]12[CH3:4])[C@:16]1([CH2:17][OH:18])[C:11](=[C:12]([CH3:23])[C:13](=O)[CH2:14][CH2:15]1)[CH2:10][CH2:9]3.O[C@H]1CC[C@H]2[C@H]3[C@H](CC[C@]12C)[C@]1(CO)C(=CC(=O)C[C@@H]1C)CC3>>[CH3:23][C:12]1[CH2:13][CH2:14][CH2:15][C@@:16]2([CH2:17][OH:18])[C:11]=1[CH2:10][CH2:9][C@@H:8]1[C@@H:19]2[CH2:20][CH2:21][C@@:3]2([CH3:4])[C@H:5]1[CH2:6][CH2:7][C@@H:2]2[OH:1]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null