original_index
int64
2
1.77M
agent_000
stringlengths
1
540
agent_001
stringlengths
1
852
agent_002
stringlengths
1
247
date_of_experiment
timestamp[ns]date
extracted_from_file
stringclasses
489 values
grant_date
timestamp[ns]date
1976-01-01 00:01:00
2016-01-01 00:09:00
is_mapped
bool
1 class
procedure_details
stringlengths
8
24.5k
product_000
stringlengths
1
484
product_001
stringlengths
1
208
reactant_000
stringlengths
1
902
reactant_001
stringlengths
1
902
reactant_002
stringlengths
1
285
rxn_str
stringlengths
87
6.12k
rxn_time
float64
0
2.16k
solvent_000
stringclasses
446 values
solvent_001
stringclasses
405 values
solvent_002
stringclasses
330 values
temperature
float64
-230
30.1k
yield_000
float64
0
90,205,156,600B
yield_001
float64
0
100M
agent_003
null
agent_004
null
agent_005
null
agent_006
null
agent_007
null
agent_008
null
agent_009
null
agent_010
null
agent_011
null
agent_012
null
agent_013
null
agent_014
null
agent_015
null
agent_016
null
solvent_003
null
solvent_004
null
solvent_005
null
solvent_006
null
solvent_007
null
solvent_008
null
solvent_009
null
solvent_010
null
1,130,195
null
null
null
null
ord_dataset-285df12e34cd46e993e3c8ebc3a8962a
2012-01-01T00:01:00
true
This compound was made from 2-bromo-5-methylbenzoic acid in the same manner as compound 18d: 1H NMR (300 MHz, DMSO-d6) δ (ppm) 2.27 (s, 3H), 3.30 (s, 3H), 4.51 (s, 2H), 4.68 (s, 2H), 7.05 (dd, J=7.9, 2.3 Hz, 1H), 7.30 (d, J=1.5 Hz, 1H), 7.46 (d, J=8.2 Hz, 1H).
COCOCc1cc(C)ccc1Br
null
COCOCc1cc(Cl)ccc1Br
Cc1ccc(Br)c(C(=O)O)c1
null
[Br:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4](O)=[O:5].BrC1C=CC(Cl)=CC=1[CH2:20][O:21][CH2:22]OC>>[Br:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[CH2:4][O:5][CH2:20][O: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
1,694,900
O=S(=O)(O)O
null
null
null
ord_dataset-c1e70ad912eb438f8d34b1dc681f809a
2016-01-01T00:02:00
true
A solution of 2-bromo-4-trifluoromethylphenylacetic acid (2.00 g, 7.07 mmol) and concentrated aqueous H2SO4 (1 mL) in MeOH (30 mL) was heated at reflux for 16 hours. The volatiles were removed under reduced pressure then the residue taken up in EtOAc. The resulting solution was washed with 10% NaHCO3, dried (MgSO4) and evaporated under reduced pressure to give the title compound A57 as a clear liquid (2.07 g, 98%); 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J=1.1 Hz, 1H), 7.53 (dd, J=8.0, 1.1 Hz, 1H), 7.41 (d, J=8.0 Hz, 1H), 3.84 (s, 2H), 3.72 (s, 3H). LCMS-A: rt 6.236 min; m/z 297/299 [M+H]+.
COC(=O)Cc1ccc(C(F)(F)F)cc1Br
null
CO
O=C(O)Cc1ccc(C(F)(F)F)cc1Br
null
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[CH2:12][C:13]([OH:15])=[O:14].OS(O)(=O)=O.[CH3:21]O>>[Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[CH2:12][C:13]([O:15][CH3:21])=[O:14]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,326,022
O=C([O-])O
[Na+]
null
null
ord_dataset-cfad8b3f00044bcda60a96b019f09872
2013-01-01T00:08:00
true
A mixture of 3,4,5,6,7,8-hexahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-one (0.8 g) and POCl3 (10 mL) was heated at 55-65° C. for 3 h. Water was then added followed by sodium bicarbonate. The resulting mixture was extracted with ethyl acetate. The organic layer was concentrated and the crude compound was purified by silica gel column chromatography using a mixture of hexanes:ethyl acetate (20:1), to give the title compound (0.52 g, 60%). 1H NMR (300 MHz, CDCl3): δ 8.69 (s, 1H), 3.10-3.07 (m, 2H), 2.88-2.86 (m, 2H), 1.89-1.92 (m, 4H). LC-MS (ESI) m/z 225.3 (M+H).
Clc1ncnc2sc3c(c12)CCCC3
null
O=P(Cl)(Cl)Cl
O=c1[nH]cnc2sc3c(c12)CCCC3
null
[N:1]1[C:6]2[S:7][C:8]3[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=3[C:5]=2[C:4](=O)[NH:3][CH:2]=1.O=P(Cl)(Cl)[Cl:17].C(=O)(O)[O-].[Na+]>O>[Cl:17][C:4]1[C:5]2[C:9]3[CH2:10][CH2:11][CH2:12][CH2:13][C:8]=3[S:7][C:6]=2[N:1]=[CH:2][N:3]=1
null
O
null
null
60
null
60
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,216,810
CC(=O)[O-]
Cl
[Na+]
null
ord_dataset-dc3bb1b1ac4e4229a3fc28fb559a9777
2012-01-01T00:10:00
true
Compound 1b (341 mg, 1.3 mmol) and sodium acetate trihydrate (513 mg, 3.8 mmol) were combined in ethanol (5 mL) and heated to reflux for 15 minutes. Hydroxylamine hydrochloride (131 mg, 1.9 mmol) was added and heating was continued for 3 h. The mixture was cooled to room temperature and diluted with water (30 mL). The mixture was chilled in an ice-bath and the resulting white precipitate was isolated by filtration, washed with water, and dried under vacuum to afford 266 mg (74%) of 1c: 1H NMR (300 MHz, CDCl3) δ 7.98 (br s, 1 H), 7.65-7.56 (m, 2 H), 7.02 (t, J=8.4 Hz, 1 H), 3.42-3.33 (m, 4 H), 3.04 (s, 3 H), 2.82 (t, J=5.9 Hz, 2 H), 2.54 (t, J=5.7 Hz, 2 H); LC-MS 287.1 (MH+).
CS(=O)(=O)c1ccc(N2CCC(=NO)CC2)c(F)c1
null
NO
CS(=O)(=O)c1ccc(N2CCC(=O)CC2)c(F)c1
O
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]1.[OH2:19].O.O.C([O-])(=O)C.[Na+].Cl.[NH2:28]O>C(O)C.O>[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][C:15](=[N:28][OH:19])[CH2:14][CH2:13]1
3
CCO
null
null
25
71.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,532,624
[Al+3]
[H-]
[Li+]
null
ord_dataset-8d5c200bca27407ab9febe7598e16458
2015-01-01T00:01:00
true
200 mg (1.10 mmol) of 1,2,3,4-tetrahydro-naphthalen-1-carboxylic acid compound was dissolved in 9 mL of tetrahydrofuran, and then 129 mg (3.30 mmol) of lithium aluminum hydride was added at 0° C. and stirred at room temperature for 1 hour. Water was slowly added to quench the reaction, and when a gel was formed by adding ethyl acetate, the celite was filtered. Then, the residue was dissolved again in 20 mL of ethyl acetate and the organic layer was washed with distilled water three times. The organic layer was dried with anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to give 180 mg of colorless oil (yield: 97%).
OCC1CCCc2ccccc21
null
O=C(O)C1CCCc2ccccc21
null
null
[CH:1]1([C:11](O)=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.C(OCC)(=O)C>O1CCCC1>[CH:1]1([CH2:11][OH:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1
1
C1CCOC1
O
CCOC(C)=O
25
null
100.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
287,105
[H-]
[Na+]
null
null
ord_dataset-3577d334f6eb4dc4bd73564fee3f0dfc
1994-01-01T00:03:00
true
To a mixture of 0.5 g of sodium hydride in 100 ml of DMF was added 2.0 g of 1-[4-(t-butyl)phenyl]ethanol, and the resulting mixture was stirred at room temperature for one hour. Then 1.8 g of 4-chloroquinazoline in 30 ml of DMF were added. The mixture was stirred at room temperature for three hours, then poured into an ice/water mixture. The product was extracted into ether, the ether solution was concentrated and the residue was recrystallized from a pentane/ethyl acetate mixture to give 0.300 g of the title product. M.P. 85°-86° C.
CC(Oc1ncnc2ccccc12)c1ccc(C(C)(C)C)cc1
null
Clc1ncnc2ccccc12
CC(O)c1ccc(C(C)(C)C)cc1
null
[H-].[Na+].[C:3]([C:7]1[CH:12]=[CH:11][C:10]([CH:13]([OH:15])[CH3:14])=[CH:9][CH:8]=1)([CH3:6])([CH3:5])[CH3:4].Cl[C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]=[CH:19][N:18]=1>CN(C=O)C>[C:3]([C:7]1[CH:8]=[CH:9][C:10]([CH:13]([O:15][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH3:14])=[CH:11][CH:12]=1)([CH3:6])([CH3:4])[CH3:5]
1
CN(C)C=O
null
null
25
null
9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
115,063
Cl
[H-]
[Na+]
null
ord_dataset-d182ca8cf3f34de69c7a38343db8c930
1984-01-01T00:03:00
true
2-Dimethylaminoethanethiol hydrochloride (3.4 g.) was added to a suspension of sodium hydride (2.32 g. of a 50% w/w dispersion in mineral oil) in dimethylformamide (25 ml.) at 0° to 5°. When all the hydrogen had evolved, 2-chloro-3-isopropylquinoline (4.0 g.) was added and the mixture heated at 80° for 5 hr. The reaction mixture was then poured into ice water (500 ml.) and extracted with ethyl acetate (3×120 ml.). The ethyl acetate extract was washed successively with water (100 ml.) and saturated brine (100 ml.) and then dried (MgSO4). The ethyl acetate solution was evaporated and the residual oil was chromatographed on basic alumina (70 g.; Brockmann Grade III), eluted with increasing concentrations of chloroform in petroleum ether. The eluate obtained with 20% v/v chloroform in petroleum ether was evaporated, the residual oil was dissolved in diethyl ether, and ethereal hydrogen chloride was added until precipitation was complete. The solid residue was collected by filtration and crystallised from ethanol-diethyl ether to give 2-(2-dimethylaminoethylthio)-3-isopropylquinoline hydrochloride, m.p. 164°-7°.
CC(C)c1cc2ccccc2nc1SCCN(C)C
null
[H][H]
CN(C)CCS
CC(C)c1cc2ccccc2nc1Cl
Cl.[CH3:2][N:3]([CH3:7])[CH2:4][CH2:5][SH:6].[H-].[Na+].[H][H].[Cl:12][C:13]1[C:22]([CH:23]([CH3:25])[CH3:24])=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=1>CN(C)C=O>[ClH:12].[CH3:2][N:3]([CH3:7])[CH2:4][CH2:5][S:6][C:13]1[C:22]([CH:23]([CH3:25])[CH3:24])=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=1
null
CN(C)C=O
null
null
0
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
898,719
N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
null
null
null
ord_dataset-de6bce51790e4004a27e1a8f2bcc7ded
2009-01-01T00:08:00
true
A suspension of 1-(2,4-dichlorophenyl)-2-(4-hydroxyphenyl)-3-methyl-5-piperidin-1-yl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one (153 mg, 0.325 mmol) and DDQ (295 mg, 1.301 mmol) in 1,4-dioxane (12 ml) was stirred at rt for 1 h and 20 min followed by 1 h and 50 min at 35° C. and 2 h and 50 min at 45° C. The solvent was evaporated and the product purified by hplc. The solvent was evaporated and water added. The product was extracted from the water phase with DCM and EtOAc. The combined organic phases were evaporated and the residue was re-suspended in toluene and evaporated to yield the product as a yellow solid (74 mg, 49%). MS m/z 468 (M+H)+.
Cc1c(-c2ccc(O)cc2)n(-c2ccc(Cl)cc2Cl)c2ccn(N3CCCCC3)c(=O)c12
null
Cc1c2c(n(-c3ccc(Cl)cc3Cl)c1-c1ccc(O)cc1)CCN(N1CCCCC1)C2=O
null
null
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17]2[CH2:16][CH2:15][N:14]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[C:13](=[O:24])[C:12]=2[C:11]([CH3:25])=[C:10]1[C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1.C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17]2[CH:16]=[CH:15][N:14]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[C:13](=[O:24])[C:12]=2[C:11]([CH3:25])=[C:10]1[C:26]1[CH:27]=[CH:28][C:29]([OH:32])=[CH:30][CH:31]=1
0.33
C1COCCO1
null
null
25
48.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,718,185
B
null
null
null
ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb
2016-01-01T00:04:00
true
To a solution of 1-(4-bromo-1-methyl-1H-pyrazol-3-yl)-5-oxopyrrolidine-3-carboxylic acid (511 mg) obtained in Step A of Example 7 in THF (3.0 mL) was added 1.1M borane-THF complex THF solution (5.0 mL) under ice-cooling. The reaction mixture was stirred at room temperature for 20 hr, and diluted with ethyl acetate. The diluted solution was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and (methanol/ethyl acetate) to give the title compound (84 mg).
Cn1cc(Br)c(N2CC(CO)CC2=O)n1
null
Cn1cc(Br)c(N2CC(C(=O)O)CC2=O)n1
null
null
[Br:1][C:2]1[C:3]([N:8]2[C:12](=[O:13])[CH2:11][CH:10]([C:14](O)=[O:15])[CH2:9]2)=[N:4][N:5]([CH3:7])[CH:6]=1.B.C1COCC1>C1COCC1.C(OCC)(=O)C>[Br:1][C:2]1[C:3]([N:8]2[CH2:9][CH:10]([CH2:14][OH:15])[CH2:11][C:12]2=[O:13])=[N:4][N:5]([CH3:7])[CH:6]=1
20
CCOC(C)=O
C1CCOC1
null
25
17.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,663,760
[Pd+2]
[OH-]
null
null
ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0
2015-01-01T00:11:00
true
A solution of (E)-1-(4-fluorophenyl)-5-(pyridin-2-ylmethylene)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-one (0.519 g, 1.354 mmol) in toluene (25 mL) containing 20% Pd(OH)2 (0.090 g, 0.128 mmol) was evacuated and placed under hydrogen. The mixture was stirred under an atmosphere of hydrogen provided via a balloon at rt for about 11 h then the catalyst was removed by filtration through Celite®. The filtrate was concentrated under reduced pressure to yield 1-(4-fluorophenyl)-5-(pyridin-2-ylmethyl)-5,7,8,9-tetrahydrocyclohepta[f]indazol-6(1H)-one (7, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (0.52 g, 100%); LC/MS, method 3, Rt=2.06 min, MS m/z 386 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.48-8.46 (m, 1H), 8.27 (d, J=0.8 Hz, 1H), 7.84-7.75 (m, 2H), 7.72-7.63 (m, 3H), 7.47-7.38 (m, 2H), 7.36 (d, J=7.8 Hz, 1H), 7.21-7.17 (m, 1H), 4.95-4.92 (m, 1H), 3.88-3.81 (m, 1H), 3.44-3.36 (m, 1H), 3.34-3.27 (m, 1H), 3.12-3.06 (m, 1H), 2.98-2.90 (m, 1H), 2.47-2.40 (m, 1H), 2.27-2.17 (m, 1H), 1.60-1.57 (m, 1H).
O=C1CCCc2cc3c(cnn3-c3ccc(F)cc3)cc2C1Cc1ccccn1
null
O=C1CCCc2cc3c(cnn3-c3ccc(F)cc3)cc2/C1=C\c1ccccn1
null
null
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]4=[C:14]([CH2:17][CH2:18][CH2:19][C:20](=[O:29])/[C:21]/4=[CH:22]/[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)[CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1>C1(C)C=CC=CC=1.[OH-].[OH-].[Pd+2]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]4[CH:21]([CH2:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=5)[C:20](=[O:29])[CH2:19][CH2:18][CH2:17][C:14]=4[CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1
null
Cc1ccccc1
null
null
null
null
99.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
477,663
[K+]
[OH-]
null
null
ord_dataset-21c1b1c06c7e4e09a38b5b1c71a32e52
2000-01-01T00:10:00
true
To a solution of 8.21 g of (RS)-3-(ethoxycarbonylmethyl)-1-(2,2-diethoxyethyl)-3-(N'-(4-methylphenyl)ureido)indolin-2-one in 100 ml of methanol was added 30 ml of an aqueous solution of 2.0 g of potassium hydroxide (85%) at room temperature, followed by stirring for 6 hours. The reaction mixture was concentrated, and the concentrate was diluted with water, which was washed with chloroform. The aqueous layer was adjusted to pH 2 by addition of 2N hydrochloric acid, and extracted with chloroform, and the organic layer was dried over anhydrous sodium sulfate and concentrated to yield 6.63 g (86%) of the title compound.
CCOC(CN1C(=O)C(CC(=O)O)(NC(=O)Nc2ccc(C)cc2)c2ccccc21)OCC
null
CCOC(=O)CC1(NC(=O)Nc2ccc(C)cc2)C(=O)N(CC(OCC)OCC)c2ccccc21
null
null
C([O:3][C:4]([CH2:6][C:7]1([NH:25][C:26]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=2)=[O:27])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]([CH2:16][CH:17]([O:21][CH2:22][CH3:23])[O:18][CH2:19][CH3:20])[C:8]1=[O:24])=[O:5])C.[OH-].[K+]>CO>[CH2:22]([O:21][CH:17]([O:18][CH2:19][CH3:20])[CH2:16][N:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:7]([CH2:6][C:4]([OH:5])=[O:3])([NH:25][C:26]([NH:28][C:29]2[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=2)=[O:27])[C:8]1=[O:24])[CH3:23]
6
CO
null
null
null
null
85.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,003,874
null
null
null
null
ord_dataset-70899a0178cc441482746c093624afa0
2010-01-01T00:10:00
true
2-amino-5-hydroxy-benzoic acid (15 mmol) are suspended in ethanol (water free, 600 ml) and heated up to 60° C. and stirred. Then triethylamine (30 mmol) is added and a clear solution is formed. Ethoxy-imino-acetic acid ethyl ester (16.5 mmol) is added at 60° C. and after 15 minutes another portion of triethylamine (15 mmol) is added and the mixture stirred for another 30 minutes. The mixture is cooled down to RT and left at RT without stirring over night. The solid material formed was filtered off, washed with ethanol/ether and dried (vacuum). A pale brown powder with mp. 258-260° C. (decomposition) is obtained.
CCOC(=O)c1nc(O)c2cc(O)ccc2n1
null
CCOC(=N)C(=O)OCC
Nc1ccc(O)cc1C(=O)O
null
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.C(N(CC)CC)C.[CH2:19]([O:21][C:22](=[O:28])[C:23](OCC)=[NH:24])[CH3:20]>C(O)C>[CH2:19]([O:21][C:22]([C:23]1[N:24]=[C:4]([OH:6])[C:3]2[C:2](=[CH:10][CH:9]=[C:8]([OH:11])[CH:7]=2)[N:1]=1)=[O:28])[CH3:20]
null
CCN(CC)CC
CCO
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
480,978
Br
null
null
null
ord_dataset-21c1b1c06c7e4e09a38b5b1c71a32e52
2000-01-01T00:10:00
true
48% hydrobromic acid (3 ml) and acetic acid (2 ml) were added to ethyl 7-amino-1-(2,4-difluoro-5-methoxyphenyl)-6-fluoro-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate (420 mg), and the mixture was stirred for 2 days while heating under reflux. After the reaction mixture was allowed to cool, solids deposited were collected by filtration. The solids were washed with water, ethanol and diethyl ether in that order and dried to obtain the title compound (108 mg) as a pale brown powder.
Cc1c(N)c(F)cc2c(=O)c(C(=O)O)cn(-c3cc(O)c(F)cc3F)c12
null
CCOC(=O)c1cn(-c2cc(OC)c(F)cc2F)c2c(C)c(N)c(F)cc2c1=O
null
null
Br.[NH2:2][C:3]1[C:12]([CH3:13])=[C:11]2[C:6]([C:7](=[O:29])[C:8]([C:24]([O:26]CC)=[O:25])=[CH:9][N:10]2[C:14]2[CH:19]=[C:18]([O:20]C)[C:17]([F:22])=[CH:16][C:15]=2[F:23])=[CH:5][C:4]=1[F:30]>C(O)(=O)C>[NH2:2][C:3]1[C:12]([CH3:13])=[C:11]2[C:6]([C:7](=[O:29])[C:8]([C:24]([OH:26])=[O:25])=[CH:9][N:10]2[C:14]2[CH:19]=[C:18]([OH:20])[C:17]([F:22])=[CH:16][C:15]=2[F:23])=[CH:5][C:4]=1[F:30]
48
CC(=O)O
null
null
null
28.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
289,217
CC(C)(N)C(C)(C)N
O=P(O)(O)O
[Li]CCCC
null
ord_dataset-96711be098434bc9ab567cb77fa3362b
1994-01-01T00:04:00
true
A 3.1 ml (5.0 mmole) portion of n-butyllithium.hexane solution was added dropwise to 1.35 g (5.0 mmole) of 1-benzyl-2,5-dimethoxy-3,4,6-trimethylbenzene and 0.83 ml (5×1.1 mmole) of 1,1,2,2-tetramethylethylenediamine dissolved in anhydrous tetrahydrofuran (15 ml), under an atmosphere of argon at 50° C. over the period of 5 minutes, followed by stirring at 50° to 55° C. for 25 minutes. Then, a solution of 0.83 (5.0 mmole) of n-hexyl bromide in tetrahydrofuran (5 ml) was added dropwise to the mixed solution over the period of 5 minutes, followed by stirring at 50° C. for further 10 minutes. The reaction solution was cooled with ice and made acid by adding a 10% aqueous phosphoric acid solution, and the product was extracted with isopropyl ether. The organic layer was separated out, washed with aqueous sodium chloride solution, dried (magnesium sulfate) and evaporated. The residual solution was chromatographed on a silica gel column to effect purification (elution with hexane/isopropyl ether) to thereby give 1.37 g (77%) of 7-(2,5-dimethoxy-3,4,6-trimethylphenyl)-7-phenylheptane. Its typical physical properties and nuclear magnetic resonance specrum data are shown in Table 14.
CCCCCCC(c1ccccc1)c1c(C)c(OC)c(C)c(C)c1OC
null
CCCCCCBr
COc1c(C)c(C)c(OC)c(Cc2ccccc2)c1C
null
C([Li])CCC.[CH2:6]([C:13]1[C:18]([CH3:19])=[C:17]([O:20][CH3:21])[C:16]([CH3:22])=[C:15]([CH3:23])[C:14]=1[O:24][CH3:25])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CC(C)(N)C(C)(C)N.[CH2:34](Br)[CH2:35][CH2:36][CH2:37][CH2:38][CH3:39].P(=O)(O)(O)O>O1CCCC1.CCCCCC>[CH3:25][O:24][C:14]1[C:15]([CH3:23])=[C:16]([CH3:22])[C:17]([O:20][CH3:21])=[C:18]([CH3:19])[C:13]=1[CH:6]([C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39]
0.42
CCCCCC
C1CCOC1
null
null
null
77
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,456,112
C[O-]
[Na+]
null
null
ord_dataset-a86112d52cd54525a5e36d41f18aced2
2014-01-01T00:07:00
true
1.5 equivalents of sodium methoxide (30% in methanol) were added to 7.79 g of thiourea in 150 ml of absolute ethanol. A solution of 30 g of 2-(3-methyl-benzoylamino)malonic acid diethyl ester in 100 ml of absolute ethanol was added dropwise, and the mixture was stirred at 60° C. for 2 h. Then the mixture was cooled to 0° C. for 30 min, and the precipitate was filtered off with suction, washed and dried. 28.6 g of the crude title compound were obtained.
Cc1cccc(C(=O)Nc2c(O)nc(S)nc2O)c1
null
CCOC(=O)C(NC(=O)c1cccc(C)c1)C(=O)OCC
NC(N)=S
null
C[O-].[Na+].[NH2:4][C:5]([NH2:7])=[S:6].C([O:10][C:11](=O)[CH:12]([NH:18][C:19](=[O:27])[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[CH:21]=1)[C:13](OCC)=[O:14])C>C(O)C>[OH:14][C:13]1[C:12]([NH:18][C:19](=[O:27])[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[CH:21]=2)=[C:11]([OH:10])[N:7]=[C:5]([SH:6])[N:4]=1
2
CCO
null
null
60
100.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,028,779
[Pd]
null
null
null
ord_dataset-83acb82dc5ba4f7aba439b9875aaac43
2011-01-01T00:02:00
true
1.56 g (5.7 mmol) of 1,1′-bi-2-naphthol are admixed with 5.7 ml (2.85 mmol) of a 0.5 M titanium tetraisopropoxide solution in toluene and the red solution is stirred for 2 hours at room temperature. 9.5 g (57.2 mmol) of 2-fluoro-6-(1-methyleneethyl)anisole and 12.5 ml (95 mmol) of ethyl trifluoropyruvate are added and the mixture is heated at 140° C. for 18 hours. After cooling it is immediately purified by column chromatography on silica gel (hexane/ethyl acetate 0-5%) to give 8.9 g of ethyl 4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pent-4-enoate. 8.9 g (26.5 mmol) of ethyl 4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pent-4-enoate are dissolved in 200 ml of methanol and 2 ml of acetic acid, and 890 mg of palladium on carbon (10%) are added. The suspension is shaken for 1.5 hours under a hydrogen atmosphere under atmospheric pressure until the hydrogen uptake is 560 ml. The mixture is filtered through Celite, the filter bed being rinsed thoroughly with ethyl acetate. Removal of the solvent gives 8.6 g of ethyl 4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanoate. 8.6 g (25.4 mmol) of ethyl 4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)-pentanoate in 350 ml of diethyl ether are cooled to −30° C. and over 15 minutes 1.7 g (44.7 mmol) of lithium aluminum hydride in solid form are added in portions. The mixture is stirred for 1.5 hours, in the course of which the temperature climbs to −15° C., followed by dropwise addition in succession of ethyl acetate and water and by a further hour of stirring until a readily filterable precipitate has formed. The suspension is filtered through Celite, the filter bed being thoroughly rinsed with ethyl acetate. The phases of the filtrate are separated and extraction is carried out again with ethyl acetate. The extracts are washed with saturated sodium chloride solution and dried over sodium sulphate and the solvent is removed in vacuo. Separation by column chromatography on silica gel (hexane/diisopropyl ether 0-15%) yields 3.1 g of (2R*,4R*)-4-(3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal
CCOC(=O)C(O)(CC(C)c1cccc(F)c1OC)C(F)(F)F
null
[H][H]
C=C(CC(O)(C(=O)OCC)C(F)(F)F)c1cccc(F)c1OC
null
[F:1][C:2]1[C:3]([O:22][CH3:23])=[C:4]([C:8](=[CH2:21])[CH2:9][C:10]([OH:20])([C:16]([F:19])([F:18])[F:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:5]=[CH:6][CH:7]=1.[H][H]>CO.C(O)(=O)C.[Pd]>[F:1][C:2]1[C:3]([O:22][CH3:23])=[C:4]([CH:8]([CH3:21])[CH2:9][C:10]([OH:20])([C:16]([F:19])([F:18])[F:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:5]=[CH:6][CH:7]=1
null
CO
CC(=O)O
null
null
95.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
766,262
CCN=C=NCCCN(C)C
Cl
null
null
ord_dataset-7a8649d55889427e85b208ae89475895
2007-01-01T00:04:00
true
To a solution of ethyl (5-carboxy-1-methylpyrazol-3-yl)oxyacetic acid (0.5 mmol) and EDCl (0.5 mmol) in methanol (20 mL) was added a solution of 1,3-diallyl-5,6-diaminouracil (0.5 mmol), dissolved in methanol (20 mL). The mixture was stirred at room temperature for two hours, the solvent was then removed in vacuo, water added, and the solid that formed was collected by filtration and washed with additional cold water. The intermediate amide was heated in 20 mL of 2.5 N NaOH at 70° C. for 30 minutes to afford the desired 2-[5-(1,3-diallyl-xanthin-8-yl)-1-methyl-pyrazol-3-yl)oxyacetic acid.
C=CCn1c(=O)c2[nH]c(-c3cc(OCC(=O)O)nn3C)nc2n(CC=C)c1=O
null
CCC(Oc1cc(C(=O)O)n(C)n1)C(=O)O
C=CCn1c(N)c(N)c(=O)n(CC=C)c1=O
null
C([CH:3]([O:7][C:8]1[CH:12]=[C:11]([C:13](O)=O)[N:10]([CH3:16])[N:9]=1)[C:4]([OH:6])=[O:5])C.CCN=C=NCCCN(C)C.Cl.[CH2:29]([N:32]1[C:39]([NH2:40])=[C:38]([NH2:41])[C:36](=[O:37])[N:35]([CH2:42][CH:43]=[CH2:44])[C:33]1=[O:34])[CH:30]=[CH2:31]>CO>[CH2:42]([N:35]1[C:36](=[O:37])[C:38]2[NH:41][C:13]([C:11]3[N:10]([CH3:16])[N:9]=[C:8]([O:7][CH2:3][C:4]([OH:6])=[O:5])[CH:12]=3)=[N:40][C:39]=2[N:32]([CH2:29][CH:30]=[CH2:31])[C:33]1=[O:34])[CH:43]=[CH2:44]
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
1,414,664
null
null
null
null
ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f
2014-01-01T00:04:00
true
L-prolinol (Compound 1) (0.61 g, 6.0 mmol) was dissolved in 70 ml of pure water, thus preparing an L-prolinol aqueous solution. N-(9-Fluorenylmethoxycarbonyloxy)succinimide (Fmoc-OSu) (2.0 g, 6.0 mmol) was dissolved in 10 ml of THF. This THF solution was added to the L-prolinol aqueous solution, and this was stirred for 1 hour so as to react the L-prolinol and the Fmoc-OSu. The reaction solution was separated into a liquid fraction and a precipitate fraction. These fractions respectively were subjected to extraction with ethyl acetate, and organic layers respectively were collected therefrom. The thus-obtained organic layers were mixed together, and anhydrous sodium sulfate was added thereto to absorb moisture (hereinafter, this process is referred to as a “drying” process). The organic layers were filtered, and the filtrate obtained was vacuum concentrated. The residual substance obtained was purified by silica gel column chromatography (the eluent hexane:ethyl acetate=1:1). Thus, Compound 2 was obtained (1.4 g, yield: 74%). The result of NMR analysis with respect to this compound is shown below.
O=C(OCC1c2ccccc2-c2ccccc21)N1CCC[C@H]1CO
null
OC[C@@H]1CCCN1
O=C(OCC1c2ccccc2-c2ccccc21)ON1C(=O)CCC1=O
null
[NH:1]1[CH2:7][CH2:6][CH2:5][C@H:2]1[CH2:3][OH:4].[CH:8]1[C:20]2[CH:19]([CH2:21][O:22][C:23](ON3C(=O)CCC3=O)=[O:24])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]=2[CH:11]=[CH:10][CH:9]=1>O.C1COCC1>[C:23]([N:1]1[CH2:7][CH2:6][CH2:5][C@H:2]1[CH2:3][OH:4])([O:22][CH2:21][CH:19]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]2[C:20]1=[CH:8][CH:9]=[CH:10][CH:11]=2)=[O:24]
1
C1CCOC1
O
null
null
null
74
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
871,171
CCOC(=O)Cl
null
null
null
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
2009-01-01T00:03:00
true
Triethylamine (6.5 μL, 0.047 mmol) and ethyl chloroformate (7 μL, 0.073 mmol) were added sequentially to a solution of (Z)-7-[(1R,2S,3R,5R)-5-chloro-2-(3,5-dichloro-phenoxymethyl)-3-hydroxy-cyclopentyl]-hept-5-enoic acid (see U.S. 60/644,069, 20 mg, 0.047 mmol) in CH2Cl2 (0.47 mL) at room temperature. After 2.5 h, triethylamine (6.5 μL, 0.047 mmol) and 4-(2-hydroxyethyl)-morpholine (58 μL, 0.47 mmol) were added. After stirring overnight at room temperature, the reaction mixture was partitioned between H2O (5 mL) and CH2Cl2 (5 mL). The phases were separated and the aqueous phase was extracted with CH2Cl2 (2×5 mL). The combined organic phase was washed with 1 N HCl (5 mL) then dried (MgSO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (5% MeOH/CH2Cl2) afforded 5.1 mg (20%) of the title compound (2).
O=C(CCC/C=C\C[C@@H]1[C@@H](COc2cc(Cl)cc(Cl)c2)[C@H](O)C[C@H]1Cl)OCCN1CCOCC1
null
OCCN1CCOCC1
O=C(O)CCC/C=C\C[C@@H]1[C@@H](COc2cc(Cl)cc(Cl)c2)[C@H](O)C[C@H]1Cl
null
C(N(CC)CC)C.ClC(OCC)=O.[Cl:14][C@H:15]1[C@H:19]([CH2:20]/[CH:21]=[CH:22]\[CH2:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])[C@@H:18]([CH2:29][O:30][C:31]2[CH:36]=[C:35]([Cl:37])[CH:34]=[C:33]([Cl:38])[CH:32]=2)[C@H:17]([OH:39])[CH2:16]1.O[CH2:41][CH2:42][N:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1>C(Cl)Cl>[N:43]1([CH2:42][CH2:41][O:27][C:26](=[O:28])[CH2:25][CH2:24][CH2:23]/[CH:22]=[CH:21]\[CH2:20][C@H:19]2[C@H:15]([Cl:14])[CH2:16][C@@H:17]([OH:39])[C@@H:18]2[CH2:29][O:30][C:31]2[CH:32]=[C:33]([Cl:38])[CH:34]=[C:35]([Cl:37])[CH:36]=2)[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1
2.5
ClCCl
CCN(CC)CC
null
25
20.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
520,721
Cl[Sn]Cl
null
null
null
ord_dataset-262b40ea420c471da9b9244fe9b8f645
2001-01-01T00:10:00
true
Tin (II) chloride (1.42 g, 7.5 mmol) was added to a solution of 5-azido-3-chloro-4-cyanopyridine (0.9 g, 5 mmol) in ethanol (20 ml) and water (0.3 ml). Bubbling ensued. The mixture was stirred for 1 h. and then extracted twice with ethyl acetate. The extracts were washed twice with saturated aqueous sodium bicarbonate and dried over sodium sulphate. Evaporation of the solvent gave the product as an oil, which was purified by flash column chromatography on silica gel, eluting with dichloromethane/metahnol (10:1) to afford the product. MS (+CI) m/z 152 [M−H]+; 1H NMR (d6-DMSO) 8.15 (1H, s), 7.87 (1H, s), 6.88 (2H, s).
N#Cc1c(N)cncc1Cl
null
N#Cc1c(Cl)cncc1N=[N+]=[N-]
null
null
[Sn](Cl)Cl.[N:4]([C:7]1[C:8]([C:14]#[N:15])=[C:9]([Cl:13])[CH:10]=[N:11][CH:12]=1)=[N+]=[N-]>C(O)C.O>[NH2:4][C:7]1[C:8]([C:14]#[N:15])=[C:9]([Cl:13])[CH:10]=[N:11][CH:12]=1
1
CCO
O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
924,097
null
null
null
null
ord_dataset-cc0899cd744f4f7f8e7f2463560faad1
2009-01-01T00:12:00
true
Add DBU (0.29 mL, 1.92 mmol) to 3-[4-(2-amino-phenoxy)-phenyl]-4-cyano-5-ethyl-1-methyl-1H-pyrrole-2-carboxylic acid ethyl ester (0.25 g, 0.64 mmol, prepared in example E-95) in methylene chloride at room temperature with stirring. After 10 minutes, cool to 0° C. and add isopropyl-sulfonylchloride (0.11 mL, 0.96 mmol). Stir the reaction mixture at 0° C. for 30 minutes and then at room temperature for 2-6 hours. Then pour the reaction mixture into water and extract with methylene chloride. Combine the organic extracts, wash with 1N HCl, water and brine, dry over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure. Purify the residue by flash chromatography eluting with acetonitrile:methylene chloride to provide the title compound.
CCOC(=O)c1c(-c2ccc(Oc3ccccc3NS(=O)(=O)C(C)C)cc2)c(C#N)c(CC)n1C
null
CCOC(=O)c1c(-c2ccc(Oc3ccccc3N)cc2)c(C#N)c(CC)n1C
CC(C)S(=O)(=O)Cl
null
C1CCN2C(=NCCC2)CC1.[CH2:12]([O:14][C:15]([C:17]1[N:18]([CH3:40])[C:19]([CH2:38][CH3:39])=[C:20]([C:36]#[N:37])[C:21]=1[C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[NH2:35])=[CH:24][CH:23]=1)=[O:16])[CH3:13].[CH:41]([S:44](Cl)(=[O:46])=[O:45])([CH3:43])[CH3:42].O>C(Cl)Cl>[CH2:12]([O:14][C:15]([C:17]1[N:18]([CH3:40])[C:19]([CH2:38][CH3:39])=[C:20]([C:36]#[N:37])[C:21]=1[C:22]1[CH:23]=[CH:24][C:25]([O:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[NH:35][S:44]([CH:41]([CH3:43])[CH3:42])(=[O:46])=[O:45])=[CH:26][CH:27]=1)=[O:16])[CH3:13]
0.17
ClCCl
C1CCC2=NCCCN2CC1
O
0
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,042,575
c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
O=C([O-])O
[Na+]
null
ord_dataset-3af92aec23dc4810b92eb0d8c60023ee
2011-01-01T00:03:00
true
Under a stream of nitrogen, 200 mg of 6-bromo-2-(4-chlorophenyl)imidazo[1,2-a]pyridine (prepared as described in 5.1), 148 mg of 2-(hydroxymethyl)phenyl boronic acid and 22.5 mg of tetrakis(triphenylphosphine)palladium are placed in a microwave tube containing a mixture of 3 ml of acetonitrile, 3 ml of toluene and 3 ml of a 2M solution of sodium hydrogen carbonate. The tube is placed in a microwave apparatus and irradiated at 150° C. for 15 min. The organic phase is separated, dried and concentrated under reduced pressure. The residue is purified by silica gel chromatography, elution being carried out with a 98/2 dichloromethane/methanol mixture. The solid obtained is triturated in diisopropyl ether and recovered by filtration and then dried in a dessicator under reduced pressure. 127 mg of compound are obtained. Mp=164-166° C. 1H NMR (DMSO-d6, δ in ppm): 4.44 (d, J=5.6 Hz, 2H); 5.19 (t, J=5.4 Hz, 1H); from 7.25 to 7.64 (m, 8H); 7.98 (m, J=8.3 Hz, 2H); 8.41 (s, 1H); 8.54 (m, 1H). M+H=335.
OCc1ccccc1-c1ccc2nc(-c3ccc(Cl)cc3)cn2c1
null
OCc1ccccc1B(O)O
Clc1ccc(-c2cn3cc(Br)ccc3n2)cc1
null
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.[OH:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1B(O)O.C(#N)C.C(=O)([O-])O.[Na+]>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.C1(C)C=CC=CC=1>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[N:10]=[C:5]3[CH:4]=[CH:3][C:2]([C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=4[CH2:19][OH:18])=[CH:7][N:6]3[CH:8]=2)=[CH:12][CH:13]=1
null
CC#N
Cc1ccccc1
null
null
null
58.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,678,182
null
null
null
null
ord_dataset-3953983e052a4076aa7cc0880b79cb8b
2016-01-01T00:01:00
true
A mixture of ethyl 4,6-dichloro-2-methylnicotinate (5.00 g, 21.36 mmol) and hydrazine monohydrate (2.1 mL, 43.3 mmol) in ethanol (22 mL) was heated to 80° C. and stirred for 17.5 h. The reaction was cooled to room temperature, diluted with water, filtered, rinsed with water, and dried under vacuum to provide 6-chloro-4-methyl-1H-pyrazolo[4,3-c]pyridin-3(2H)-one, which was carried onto the next step without further purification. MS ESI calc'd. for C7H6ClN3O [M+1]+ 184. found 184.
Cc1nc(Cl)cc2[nH][nH]c(=O)c12
null
CCOC(=O)c1c(Cl)cc(Cl)nc1C
NN
null
Cl[C:2]1[C:7]([C:8](OCC)=[O:9])=[C:6]([CH3:13])[N:5]=[C:4]([Cl:14])[CH:3]=1.O.[NH2:16][NH2:17]>C(O)C.O>[Cl:14][C:4]1[N:5]=[C:6]([CH3:13])[C:7]2[C:8](=[O:9])[NH:16][NH:17][C:2]=2[CH:3]=1
17.5
O
CCO
null
80
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,096,370
[Li+]
[OH-]
null
null
ord_dataset-af85e6f81c2d49f08086afd6d9e6959c
2011-01-01T00:10:00
true
To a solution of 5.1 (0.90 g, 2.7 mmol) in THF/MeOH (2/1) (18 mL), was added lithium hydroxide (6.0 mL, 6.0 mmol). The resulting mixture was stirred overnight at 23° C. and then quenched with excess 1N HCl. The mixture was then extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated. The crude residue was purified by combiflash (0 to 40% EtOAc/hexanes) to afford a 20.1 (0.68 g, 91% yield).
CCCCOc1cc(C(=O)O)ccc1Br
null
CCCCOC(=O)c1ccc(Br)c(OCCCC)c1
null
null
[Br:1][C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8]CCCC)=[O:7])=[CH:4][C:3]=1[O:15][CH2:16][CH2:17][CH2:18][CH3:19].[OH-].[Li+]>C1COCC1.CO>[Br:1][C:2]1[CH:14]=[CH:13][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[O:15][CH2:16][CH2:17][CH2:18][CH3:19]
8
C1CCOC1
CO
null
23
null
92.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,130,203
Cl
[Li]CCCC
null
null
ord_dataset-285df12e34cd46e993e3c8ebc3a8962a
2012-01-01T00:01:00
true
To a solution of 5b (73.2 g, 293 mmol) in dry THF (400 mL) was added n-butyllithium (1.6 M in hexanes; 200 mL) over 45 min at −78° C. under nitrogen atmosphere. Anion precipitated. After 5 min, (i-PrO)3B (76.0 mL, 330 mmol) was added over 10 min, and the mixture was allowed to warm to room temperature over 1.5 h. Water and 6 N HCl (55 mL) were added, and the solvent was removed under reduced pressure to about a half volume. The mixture was poured into ethyl acetate and water. The organic layer was washed with brine and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure. To a solution of the residue in tetrahydrofuran (360 mL) was added 6 N HCl (90 mL), and the mixture was stirred at 30° C. overnight. The solvent was removed under reduced pressure to about a half volume. The mixture was poured into ethyl acetate and water. The organic layer was washed with brine and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure, and the residue was treated with i-Pr2O/hexane to give 19b (26.9 g, 60%) as a white powder: mp 118-120° C.; 1H NMR (300 MHz, DMSO-d6) δ (ppm) 4.95 (s, 2H), 7.15 (m, 1H), 7.24 (dd, J=9.7, 1.8 Hz, 1H), 7.74 (dd, J=8.2, 6.2 Hz, 1H), 9.22 (s, 1H); ESI-MS m/z 151 (M−H)−; HPLC purity 97.8%; Anal (C7H6BFO2) C, H.
OB1OCc2cc(F)ccc21
null
CC(C)OB(OC(C)C)OC(C)C
COCOCc1cc(F)ccc1Br
null
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][O:10]COC.C([Li])CCC.[B:19](OC(C)C)(OC(C)C)[O:20]C(C)C.Cl>C1COCC1.O>[F:8][C:5]1[CH:6]=[CH:7][C:2]2[B:19]([OH:20])[O:10][CH2:9][C:3]=2[CH:4]=1
0.08
C1CCOC1
O
null
25
60.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,146,917
null
null
null
null
ord_dataset-68715347640045adb1b09e6a04722b0e
2012-01-01T00:03:00
true
5.70 g (25.0 mmol) of ethyl-3-amino-3-(4-chlorophenyl)propanoate [V. Wehner et al., Synthesis 14, 2023-2036 (2002)], 3.993 ml (27.5 mmol) of methyl 4-methyl-3-oxopentanoate and 2.87 ml (50.1 mmol) of acetic acid were taken up in 70 ml of benzene and reacted at reflux on a water separator overnight. After cooling, the mixture was washed with saturated aqueous sodium bicarbonate solution, the organic phase was dried with magnesium sulfate and the solvent was destilled off under reduced pressure. This gave 8.57 g (68% of theory) of the target compound in a purity of 70%. The fraction was used without further work-up for the subsequent steps.
CCOC(=O)CC(NC(=CC(=O)OC)C(C)C)c1ccc(Cl)cc1
null
COC(=O)CC(=O)C(C)C
CCOC(=O)CC(N)c1ccc(Cl)cc1
null
[CH2:1]([O:3][C:4](=[O:15])[CH2:5][CH:6]([NH2:14])[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1)[CH3:2].[CH3:16][CH:17]([CH3:25])[C:18](=O)[CH2:19][C:20]([O:22][CH3:23])=[O:21].C(O)(=O)C.O>C1C=CC=CC=1>[Cl:13][C:10]1[CH:9]=[CH:8][C:7]([CH:6]([NH:14][C:18]([CH:17]([CH3:25])[CH3:16])=[CH:19][C:20]([O:22][CH3:23])=[O:21])[CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:15])=[CH:12][CH:11]=1
8
O
c1ccccc1
CC(=O)O
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
601,950
null
null
null
null
ord_dataset-82e842e611ef4a05b6e7f9ea0a46d52d
2003-01-01T00:07:00
true
The title compound, white solid, m.p.=180-183° C., MS: m/e=325.4 (M+H+) was prepared in accordance with the general method of example 6 from 9H-xanthene-9-carbonyl chloride and carbamic acid butyl ester.
CCCCOC(=O)NC(=O)C1c2ccccc2Oc2ccccc21
null
O=C(Cl)C1c2ccccc2Oc2ccccc21
CCCCOC(N)=O
null
[CH:1]1[C:14]2[CH:13]([C:15](Cl)=[O:16])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[O:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH2:18]([O:22][C:23](=[O:25])[NH2:24])[CH2:19][CH2:20][CH3:21]>>[CH2:18]([O:22][C:23](=[O:25])[NH:24][C:15]([CH:13]1[C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[O:6][C:5]2[C:14]1=[CH:1][CH:2]=[CH:3][CH:4]=2)=[O:16])[CH2:19][CH2:20][CH3:21]
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
253,079
CC(=O)[O-]
[Pb+4]
null
null
ord_dataset-49bd993346b64eeeb2a8fe2643164a0a
1992-01-01T00:08:00
true
20.0 g (46.8 mmol) of t-butyl (4S,5S)-4-(cyclohexylmethyl)-5-[(2S,3RS)-3,4-dihydroxy-2-isopropylbutyl]-2,2-dimethyl-3-oxazolidinecarboxylate are dissolved in 250 ml of benzene, cooled to 5° and treated portionwise within 10 minutes with 20.8 g (47 mmol) of lead tetraacetate. After stirring at 5° for 4 hours 500 ml of ether are added and the reaction mixture is stirred for a further 15 minutes. Thereafter, the reaction mixture is filtered and the filtrate is evaporated under reduced pressure. Chromatography of the residue on 300 g of silica gel with methylene chloride as the eluting agent yields 15.9 g of t-butyl (4S,5S)-4-(cyclohexylmethyl)-5-[(S)-2-formyl-3-methylbutyl]-2,2-dimethyl-3-oxazolidinecarboxylate as an oil, MS: 380 (M-CH3)+.
CC(C)[C@@H](C=O)C[C@@H]1OC(C)(C)N(C(=O)OC(C)(C)C)[C@H]1CC1CCCCC1
null
CC(C)[C@H](C[C@@H]1OC(C)(C)N(C(=O)OC(C)(C)C)[C@H]1CC1CCCCC1)C(O)CO
null
null
[CH:1]1([CH2:7][C@H:8]2[C@H:12]([CH2:13][C@@H:14]([CH:19]([CH3:21])[CH3:20])[CH:15]([OH:18])CO)[O:11][C:10]([CH3:23])([CH3:22])[N:9]2[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4].CCOCC>C1C=CC=CC=1>[CH:1]1([CH2:7][C@H:8]2[C@H:12]([CH2:13][C@H:14]([CH:15]=[O:18])[CH:19]([CH3:21])[CH3:20])[O:11][C:10]([CH3:22])([CH3:23])[N:9]2[C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
0.25
CCOCC
c1ccccc1
null
null
null
85.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
772,545
null
null
null
null
ord_dataset-8214eb8444a44dc2900ccb42dbeff15e
2007-01-01T00:05:00
true
4,6-Dichloroquinoline (De, D., Byers L. D., Krogstad, D. J. J. Heterocyclic Chem. 1997, 34, 315) (0.34 g, 1.7 mmol) and 1-tert-butoxycarbonylpiperazine (1.58 g, 8.5 mmol) are reacted according to method A. The Boc group is cleaved with trifluoroacetic acid (5 mL) in CH2Cl2 (5 mL) giving 0.25 g of the product.
Clc1ccc2nccc(N3CCNCC3)c2c1
null
CC(C)(C)OC(=O)N1CCNCC1
Clc1ccc2nccc(Cl)c2c1
null
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.C(OC([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][CH:3]=[C:2]2[N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1
null
O=C(O)C(F)(F)F
ClCCl
null
null
59.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
369,269
N
null
null
null
ord_dataset-15cdba4c7f064b3f9cd7343cb3187881
1997-01-01T00:07:00
true
A solution of 569 mg (1 mmole) of (56) in 20 mL of NH3 /MeOH was stirred in a sealed flask at room temperature for 5 hr. Volatile materials were removed by evaporation. The residue was recrystallized from MeOH to give 337 mg (2 crops, 76%) of 57. Its 1H NMR spectrum was identical to that of (57) prepared by a direct bromination; see Method B.
OC[C@H]1O[C@@H](n2c(Cl)nc3cc(Br)c(Br)cc32)[C@H](O)[C@@H]1O
null
CC(=O)OC[C@H]1O[C@@H](n2c(Cl)nc3cc(Br)c(Br)cc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
null
null
[Cl:1][C:2]1[N:6]([C@@H:7]2[O:19][C@H:18]([CH2:20][O:21]C(=O)C)[C@@H:13]([O:14]C(=O)C)[C@H:8]2[O:9]C(=O)C)[C:5]2[CH:25]=[C:26]([Br:30])[C:27]([Br:29])=[CH:28][C:4]=2[N:3]=1>N.CO>[Cl:1][C:2]1[N:6]([C@@H:7]2[O:19][C@H:18]([CH2:20][OH:21])[C@@H:13]([OH:14])[C@H:8]2[OH:9])[C:5]2[CH:25]=[C:26]([Br:30])[C:27]([Br:29])=[CH:28][C:4]=2[N:3]=1
null
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,128,180
null
null
null
null
ord_dataset-285df12e34cd46e993e3c8ebc3a8962a
2012-01-01T00:01:00
true
The title compounds were prepared in accordance with the general method of Example 108(B), from 5-phenyl-1-(4-trimethylsilanyl-but-3-ynyl)-1H-pyrazole and 5-phenyl-2-(4-trimethylsilanyl-but-3-ynyl)-2H-pyrazole (300 mg, 1.12 mmol). The crude residue was purified by flash chromatography (cyclohexane/AcOEt 9:1) to yield 29 mg (0.15 mmol, 13%) of 2-but-3-ynyl-5-phenyl-2H-pyrazole and 13 mg (66 μmol, 6%) of 1-but-3-ynyl-5-phenyl-1H-pyrazole.
C#CCCn1ccc(-c2ccccc2)n1
C#CCCn1nccc1-c1ccccc1
C[Si](C)(C)C#CCCn1nccc1-c1ccccc1
C[Si](C)(C)C#CCCn1ccc(-c2ccccc2)n1
null
[C:1]1([C:7]2[N:11]([CH2:12][CH2:13][C:14]#[C:15][Si](C)(C)C)[N:10]=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:20]1([C:26]2[CH:27]=[CH:28][N:29]([CH2:31][CH2:32][C:33]#[C:34][Si](C)(C)C)[N:30]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[CH2:31]([N:29]1[CH:28]=[CH:27][C:26]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:30]1)[CH2:32][C:33]#[CH:34].[CH2:12]([N:11]1[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:8][CH:9]=[N:10]1)[CH2:13][C:14]#[CH:15]
null
null
null
null
null
13
6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
511,475
CN(C)c1ccncc1
null
null
null
ord_dataset-85c00026681b46f89ef8634d2b8618c3
2001-01-01T00:07:00
true
To a solution of sulfisoxazole (267 mg, 1.00 mmol) in DMF (10 ml) was added succinic anhydride (1.00 g, 10.0 mmol) and 4-dimethylaminopyridine (122 mg, 1.00 mmol). The reaction mixture was stirred at 80° C. for 2 hours and then concentrated. The residue was taken up in 5% aqueous sodium bicarbonate solution and extracted with ethyl acetate. The aqueous solution was acidified with dilute hydrochloric acid and organic material was extracted into ethyl acetate. The organic phase was washed with dilute hydrochloric acid, water and brine, treated with active charcoal and dried (MgSO4). The solution was filtered and concentrated to give 280 mg (76%) of white solid. The structure was verified by 1H (300 MHz) and 13C (75 MHz) NMR spectroscopy. Further characterisation was carried out using MALDI mass spectrometry (ACH matrix), giving a M+Na peak at m/z 390 and a M+K peak at m/z 406 as expected.
Cc1noc(NS(=O)(=O)c2ccc(NC(=O)CCC(=O)O)cc2)c1C
null
O=C1CCC(=O)O1
Cc1noc(NS(=O)(=O)c2ccc(N)cc2)c1C
null
[CH3:1][C:2]1[C:3]([CH3:18])=[N:4][O:5][C:6]=1[NH:7][S:8]([C:11]1[CH:12]=[CH:13][C:14]([NH2:17])=[CH:15][CH:16]=1)(=[O:10])=[O:9].[C:19]1(=[O:25])[O:24][C:22](=[O:23])[CH2:21][CH2:20]1>CN(C=O)C.CN(C)C1C=CN=CC=1>[CH3:18][C:3]1[C:2]([CH3:1])=[C:6]([NH:7][S:8]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:19](=[O:25])[CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[CH:13][CH:12]=2)(=[O:10])=[O:9])[O:5][N:4]=1
2
CN(C)C=O
null
null
80
null
76.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
283,047
null
null
null
null
ord_dataset-769fac6048e548eca2d49e48f972884b
1994-01-01T00:01:00
true
Dissolve 8-bromooctanoic acid (1.0g) in anhydrous toluene (3 mL) and add triphenylphosphine (1.21g). Heat to reflux overnight. Separate the lower phase crystallize (ethanol/ethyl ether) to give (8-carboxyoctyl)triphenylphosphonium bromide (1.0g).
O=C(O)CCCCCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
[Br-]
c1ccc(P(c2ccccc2)c2ccccc2)cc1
O=C(O)CCCCCCCBr
Cc1ccccc1
[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([OH:11])=[O:10].[C:12]1([P:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[C:31]1(C)C=CC=CC=1>>[Br-:1].[C:9]([CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:31][P+:18]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)([OH:11])=[O:10]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,381,213
null
null
null
null
ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81
2013-01-01T00:12:00
true
Phenyl 3-tert-butyl-1-(2-methylpyridin-3-yl)-1H-pyrazol-5-ylcarbamate (105 mg, 0.3 mmol) was treated with 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline (89 mg, 0.30 mmol) (prepared as described in Example 113A) using the procedure in Example 115C to afford 1-(3-tert-butyl-1-(2-methylpyridin-3-yl)-1H-pyrazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea (33 mg, 0.06 mmol, 20%). 1H NMR (300 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.60 (d, 1H), 8.54 (s, 1H), 8.35 (s, 1H), 7.80 (d, 1H), 7.54 (s, 2H), 7.45-7.32 (m, 3H), 7.12 (d, 1H), 6.91 (d, 1H), 6.35 (s, 1H), 3.99 (s, 3H), 3.97 (s, 3H), 2.20 (s, 3H) 1.25 (s, 9H); LC-MS (ESI) m/z 554 (M+H)+.
COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)nn4-c4cccnc4C)c3)c2cc1OC
null
COc1cc2ncnc(Oc3cccc(N)c3)c2cc1OC
Cc1ncccc1-n1nc(C(C)(C)C)cc1NC(=O)Oc1ccccc1
null
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11](=[O:19])OC2C=CC=CC=2)[N:7]([C:20]2[C:21]([CH3:26])=[N:22][CH:23]=[CH:24][CH:25]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:27][O:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][C:38]=1[O:39][CH3:40])[N:35]=[CH:34][N:33]=[C:32]2[O:41][C:42]1[CH:43]=[C:44]([CH:46]=[CH:47][CH:48]=1)[NH2:45]>>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:45][C:44]2[CH:46]=[CH:47][CH:48]=[C:42]([O:41][C:32]3[C:31]4[C:36](=[CH:37][C:38]([O:39][CH3:40])=[C:29]([O:28][CH3:27])[CH:30]=4)[N:35]=[CH:34][N:33]=3)[CH:43]=2)=[O:19])[N:7]([C:20]2[C:21]([CH3:26])=[N:22][CH:23]=[CH:24][CH:25]=2)[N:6]=1)([CH3:2])([CH3:3])[CH3:4]
null
null
null
null
null
null
20
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,703,118
Cl
null
null
null
ord_dataset-54347fcace774f89850681d6dec8009f
2016-01-01T00:03:00
true
Conc. HCl (1 mL) was added to a solution of 3-aminocyclohexanecarboxylic acid (500 mg, 3.49 mmol) in EtOH (20 mL) and stirring was continued at reflux temperature for 3 h. The reaction mixture was concentrated under reduced pressure to afford the crude, which was washed with 10% aqueous NaHCO3 solution, extracted with DCM, dried over anhydrous sodium sulphate to afford 300 mg of the title compound.
CCOC(=O)C1CCCC(N)C1
null
NC1CCCC(C(=O)O)C1
CCO
null
Cl.[NH2:2][CH:3]1[CH2:8][CH2:7][CH2:6][CH:5]([C:9]([OH:11])=[O:10])[CH2:4]1.[CH3:12][CH2:13]O>>[NH2:2][CH:3]1[CH2:8][CH2:7][CH2:6][CH:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4]1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
738,738
[H-]
[Na+]
null
null
ord_dataset-76dd1b78ee414d2da0ed30700ef026f7
2006-01-01T00:10:00
true
To a stirred solution of N-[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]-2-(tritylamino)acetamide (2 g) in N,N-dimethylformamide (20 ml) was added sodium hydride (245 mg, 60% oil suspension) at 0° C., and the mixture was stirred for 30 minutes with warming to room temperature. The mixture was cooled to 0° C., and methyl iodide (1.3 g) was added. The whole mixture was stirred at room temperature overnight. Water (5 ml) was added, and the whole mixture was extracted with ethyl acetate. The organic layer was washed with water and brine and dried over magnesium sulfate. Evaporation of the solvent under reduced pressure gave N-methyl-N-[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]-2-(tritylamino)acetamide (2.05 g).
CN(C(=O)CNC(c1ccccc1)(c1ccccc1)c1ccccc1)c1cnn(C)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
null
Cn1ncc(NC(=O)CNC(c2ccccc2)(c2ccccc2)c2ccccc2)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
CI
null
[CH3:1][N:2]1[C:6]([NH:7][C:8]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[C:5]([NH:27][C:28](=[O:50])[CH2:29][NH:30][C:31]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:4]=[N:3]1.[H-].[Na+].[CH3:53]I.O>CN(C)C=O>[CH3:53][N:27]([C:5]1[CH:4]=[N:3][N:2]([CH3:1])[C:6]=1[NH:7][C:8]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:28](=[O:50])[CH2:29][NH:30][C:31]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1
0.5
CN(C)C=O
O
null
25
null
100.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
972,025
null
null
null
null
ord_dataset-03ba810b7f464a06b5d8787af2e8b64e
2010-01-01T00:06:00
true
The mixture 85.6 mg of 7-benzylamino-5-chloro-3-isopropylpyrazolo[4,3-d]pyrimidine XVI, 0.21 mL of heptyl amine and 1 mL of pentanol was heated at 125° C. for 12 hours. The reaction mixture was evaporated to dryness in vacuo and then chromatographed on silica gel. The mixture of chloroform/acetone/heptane (1:1:1) was used as a mobile phase. Yield=60%; white syrupy; MS (ES+): 381.0 (100%, M+H+). 1H-NMR (300 MHz, CDCl3): 0.86 t (3H, J=6.6 Hz), 1.22-1.36 m (12H), 1.56 m (2H), 1.64 m (2H), 3.12 sept (1H, J=7.1 Hz), 3.41 d (2H, J=5.2 Hz), 4.79 bs (2H), 7.19-7.35 m (5H), 7.60 s (1H).
CCCCCCCNc1nc(NCc2ccccc2)c2[nH]nc(C(C)C)c2n1
null
CCCCCCCN
CC(C)c1n[nH]c2c(NCc3ccccc3)nc(Cl)nc12
null
[CH2:1]([NH:8][C:9]1[C:10]2[NH:18][N:17]=[C:16]([CH:19]([CH3:21])[CH3:20])[C:11]=2[N:12]=[C:13](Cl)[N:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:22]([NH2:29])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].C(O)CCCC>>[CH2:1]([NH:8][C:9]1[C:10]2[NH:18][N:17]=[C:16]([CH:19]([CH3:21])[CH3:20])[C:11]=2[N:12]=[C:13]([NH:29][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[N:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
null
CCCCCO
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
602,425
[Na+]
null
null
null
ord_dataset-82e842e611ef4a05b6e7f9ea0a46d52d
2003-01-01T00:07:00
true
3.7 cm3 of a 0.1M solution of sodium metaperiodate in water is added to a solution of 172 mg of the product obtained in Example 4 in 12 cm3 of methanol. The reaction medium is agitated for 1 hour 30 minutes and 3.4 cm3 of methanol and 0.6 cm3 of the metaperiodate solution are added, after 3 hours 30 minutes of agitation the reaction medium is poured into water, extracted with ethyl acetate, washed with salt water and evaporated to dryness under reduced pressure. 176 mg of residue is obtained which is chromatographed on silica twice (eluant methylene chloride-methanol (92.5-7.5)). 107 mg of desired product is collected.
C[C@]12C[C@H](c3ccc(OCCCCCS(=O)Cc4ccccn4)cc3)[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1CC[C@@H]2O
null
[O-][I+3]([O-])([O-])[O-]
C[C@]12C[C@H](c3ccc(OCCCCCSCc4ccccn4)cc3)[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1CC[C@@H]2O
null
I([O-])(=O)(=O)=O.[Na+].[N:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:13][S:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([C@H:27]2[CH2:44][C@@:42]3([CH3:43])[C@@H:38]([CH2:39][CH2:40][C@@H:41]3[OH:45])[C@H:37]3[C@H:28]2[C:29]2[CH:30]=[CH:31][C:32]([OH:46])=[CH:33][C:34]=2[CH2:35][CH2:36]3)=[CH:23][CH:22]=1.I([O-])(=O)(=O)=[O:48]>O.CO>[N:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:13][S:14]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]1[CH:22]=[CH:23][C:24]([C@H:27]2[CH2:44][C@@:42]3([CH3:43])[C@@H:38]([CH2:39][CH2:40][C@@H:41]3[OH:45])[C@H:37]3[C@H:28]2[C:29]2[CH:30]=[CH:31][C:32]([OH:46])=[CH:33][C:34]=2[CH2:35][CH2:36]3)=[CH:25][CH:26]=1)=[O:48]
0.5
O
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
216,075
null
null
null
null
ord_dataset-67ed03c283094854909157b1038e38e3
1990-01-01T00:10:00
true
20.8 g 2-(3-methyl-xanthine-7-yl)-acetaldehyde (Formula IV)-prepared similarly like 7-theophyllinyl acetaldehyde Il Farmaco, Ed. Sc. 17, 73; (1962), 40.0 ethylene glycol (Formula II) 2.5 g DOWEX 50 W synthetic resin and 1,000.0 cm3 toluene are heated under stirring in a flask equipped with a water condenser and a cooler until water condensation ceases. The reaction mixture is filtered hot and the precipitate is washed with hot toluene and the filtrate is washed upon cooling with 5% sodium hydrogen carbonate and the organic layer is evaporated after drying. The residue is crystallized three times from propanol and 2-[(3-methyl-xanthine-7-yl)methyl]-1,3-dioxolane is obtained with a yield of 55%, melting point 276°-278° C.
Cn1c(=O)[nH]c(=O)c2c1ncn2CC1OCCO1
null
Cn1c(=O)c2c(ncn2CC=O)n(C)c1=O
Cn1c(=O)[nH]c(=O)c2c1ncn2CC=O
null
[CH3:1][N:2]1[C:10]2[N:9]=[CH:8][N:7]([CH2:11][CH:12]=[O:13])[C:6]=2[C:5](=[O:14])[NH:4][C:3]1=[O:15].N1([C:27](=[O:28])[C:26]2N(CC=O)C=NC=2N(C)C1=O)C.C(O)CO.C1(C)C=CC=CC=1>O>[CH3:1][N:2]1[C:10]2[N:9]=[CH:8][N:7]([CH2:11][CH:12]3[O:28][CH2:27][CH2:26][O:13]3)[C:6]=2[C:5](=[O:14])[NH:4][C:3]1=[O:15]
null
Cc1ccccc1
O
OCCO
null
null
55
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
663,035
null
null
null
null
ord_dataset-5a3d853c53674888a5691dce2e398792
2005-01-01T00:03:00
true
To a solution of 4-(3-trifluoromethyl-phenyl)-1,3-dihydro-indol-2-one (69.3 mg, 0.25 mmol) and 3,5-dimethyl-4-(4-methyl-piperazine-1-carbonyl)-1H-pyrrole-2-carbaldehyde (64.8 mg, 0.26 mmol) in ethanol (2 mL) was added piperidine (3 drops). The reaction mixture was stirred at room temperature for three days. The solvent was evaporated and the solid was washed by ether for three times to provide pure product 3-[3,5-dimethyl-4-(4-methyl-piperazine-1-carbonyl)-1H-pyrrol-2-ylmethylene]-4-(3-trifluoromethyl-phenyl)-1,3-dihydro-indol-2-one (96.5 mg, 76%).
Cc1[nH]c(C=C2C(=O)Nc3cccc(-c4cccc(C(F)(F)F)c4)c32)c(C)c1C(=O)N1CCN(C)CC1
null
Cc1[nH]c(C=O)c(C)c1C(=O)N1CCN(C)CC1
O=C1Cc2c(cccc2-c2cccc(C(F)(F)F)c2)N1
null
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[C:5]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH2:11][C:12](=[O:18])[NH:13]3)[CH:6]=[CH:7][CH:8]=1.[CH3:21][C:22]1[C:26]([C:27]([N:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]2)=[O:28])=[C:25]([CH3:36])[NH:24][C:23]=1[CH:37]=O>C(O)C.N1CCCCC1>[CH3:21][C:22]1[C:26]([C:27]([N:29]2[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH2:34]2)=[O:28])=[C:25]([CH3:36])[NH:24][C:23]=1[CH:37]=[C:11]1[C:10]2[C:14](=[CH:15][CH:16]=[CH:17][C:9]=2[C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:19])[F:20])[CH:4]=2)[NH:13][C:12]1=[O:18]
72
C1CCNCC1
CCO
null
25
null
75.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
499,066
null
null
null
null
ord_dataset-18e9ed24dbd44e98b33bdc22aa7580a8
2001-01-01T00:04:00
true
Prepare by the method of Example 7.1 using 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine (prepared from (−)-3-(2-hydroxyethyl)-3-phenylpyrrolidine (R,R)-di-p-anisoyltartaric acid salt) and 1-chloro-3-methylbut-2-ene to give the title compound.
COc1cc(C(=O)N2CCC(CCN3CCC(Nc4nc5ccccc5n4CC=C(C)C)CC3)(c3ccccc3)C2)cc(OC)c1OC
null
CC(C)=CCCl
COc1cc(C(=O)N2CCC(CCN3CCC(Nc4nc5ccccc5[nH]4)CC3)(c3ccccc3)C2)cc(OC)c1OC
null
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:37]=[C:38]([O:42][CH3:43])[C:39]=1[O:40][CH3:41])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:19][CH2:20][N:21]2[CH2:26][CH2:25][CH:24]([NH:27][C:28]3[NH:32][C:31]4[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=4[N:29]=3)[CH2:23][CH2:22]2)([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:9]1)=[O:7].Cl[CH2:45][CH:46]=[C:47]([CH3:49])[CH3:48]>>[CH3:43][O:42][C:38]1[CH:37]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:39]=1[O:40][CH3:41])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:19][CH2:20][N:21]2[CH2:26][CH2:25][CH:24]([NH:27][C:28]3[N:29]([CH2:45][CH:46]=[C:47]([CH3:49])[CH3:48])[C:30]4[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=4[N:32]=3)[CH2:23][CH2:22]2)([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:9]1)=[O:7]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,259,319
null
null
null
null
ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0
2013-01-01T00:02:00
true
To a solution of 1,4-dimethylsulphonyl-2-butene (2.15 g, 11.64 mmol) in dichloromethane (40 ml), 4-methoxybenzylamine (6 ml, 44.24 mmol) was added dropwise and the solution was stirred 20 hours at r.t. The solid was filtrated and the filtrate was washed with water (2×30 ml), dried over Na2SO4, filtered and concentrated. The crude was purified by flash chromatography: silica gel, gradient hexane:ethyl acetate 3:1 to 1:1 to afforded the product (1.4 g, 63%) as yellow oil.
COc1ccc(CN2CC=CC2)cc1
null
COc1ccc(CN)cc1
CS(=O)(=O)CC=CCS(C)(=O)=O
null
CS([CH2:5][CH:6]=[CH:7][CH2:8]S(C)(=O)=O)(=O)=O.[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH2:20])=[CH:17][CH:16]=1>ClCCl>[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][N:20]2[CH2:8][CH:7]=[CH:6][CH2:5]2)=[CH:17][CH:16]=1
20
ClCCl
null
null
25
null
63.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
619,039
CCOC(=O)C1CCCN(C(=O)c2ccccc2)C1
null
null
null
ord_dataset-2952e63264f5422a84e12cca1e0541ee
2003-01-01T00:12:00
true
This reaction was run in the same manner as ethyl 1-benzoyl-3-piperidinecarboxylate, starting with ethyl 4-methyl-3-piperidinecarboxylate (531.8 mg; 3.11 mmol), diisopropylethylamine (600 μl; 3.44 mmol), and thiopheneacetyl chloride (382 μl; 3.11 mmol). The crude product was purified by chromatography on silica eluting with 50% ethyl acetate/50% hexane, giving ethyl 1-(2-thiopheneacetyl)-4-methyl-3-piperidinecarboxylate (681.2 mg) as a yellow oil. MS m/z (positive ion) 397 (MH++Et3N; 70), 296 (MH+; 100).
CCOC(=O)C1CN(C(=O)Cc2cccs2)CCC1C
null
O=C(Cl)Cc1cccs1
CCOC(=O)C1CNCCC1C
null
C(N1CCCC(C(OCC)=O)C1)(=O)C1C=CC=CC=1.[CH3:20][CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH:22]1[C:27]([O:29][CH2:30][CH3:31])=[O:28].C(N(C(C)C)CC)(C)C.[S:41]1[CH:45]=[CH:44][CH:43]=[C:42]1[CH2:46][C:47](Cl)=[O:48]>>[S:41]1[CH:45]=[CH:44][CH:43]=[C:42]1[CH2:46][C:47]([N:24]1[CH2:25][CH2:26][CH:21]([CH3:20])[CH:22]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:23]1)=[O:48]
null
CCN(C(C)C)C(C)C
null
null
null
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
1,527,807
Cl
null
null
null
ord_dataset-8c74302143c04eb9983e4b3a7ead2d72
2014-01-01T00:12:00
true
The title compound was prepared from the product of Example 1, step J, and trans-4-(trifluoromethyl)-cinnamic acid, by the method of Example 1, step K, giving a solid that was mostly the more polar cyclohexyl diastereomer by LCMS. Mass spectrum (LCMS, ESI pos.) calcd. for C31H35F3N4O2: 553 (M+H). Found: 553
NC(=O)C(NC1CCC(c2c[nH]c3ccccc23)CC1)C1CCN(C(=O)/C=C/c2ccc(C(F)(F)F)cc2)CC1
null
O=C(O)/C=C/c1ccc(C(F)(F)F)cc1
NC(=O)C(NC1CCC(c2c[nH]c3ccccc23)CC1)C1CCNCC1
null
Cl.Cl.[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH:12]2[CH2:17][CH2:16][CH:15]([NH:18][CH:19]([CH:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)[C:20]([NH2:22])=[O:21])[CH2:14][CH2:13]2)=[CH:4]1.[F:29][C:30]([F:43])([F:42])[C:31]1[CH:41]=[CH:40][C:34](/[CH:35]=[CH:36]/[C:37](O)=[O:38])=[CH:33][CH:32]=1>>[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH:12]2[CH2:17][CH2:16][CH:15]([NH:18][CH:19]([CH:23]3[CH2:24][CH2:25][N:26]([C:37](=[O:38])/[CH:36]=[CH:35]/[C:34]4[CH:33]=[CH:32][C:31]([C:30]([F:42])([F:43])[F:29])=[CH:41][CH:40]=4)[CH2:27][CH2:28]3)[C:20]([NH2:22])=[O:21])[CH2:14][CH2:13]2)=[CH:4]1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
958,099
null
null
null
null
ord_dataset-ed65749688da45af8a8432967b017729
2010-01-01T00:05:00
true
A solution of D8 (120 mg), benzoic acid chloride (87 μl), NEt3 (150 μl) in THF (1 ml) and CH2Cl2 (3 ml) is stirred at RT for 3 h. After evaporation EtOAc is added and the organic phase is washed with saturated NaHCO3 solution and brine, dried over MgSO4 and evaporated again. The residue is purified by preparative RP-HPLC to give the desired compound (13.4 mg).
CC1(C)C(=O)N(CCC2CC2)c2cc3[nH]c(NC(=O)c4ccccc4)nc3cc21
null
O=C(Cl)c1ccccc1
CC1(C)C(=O)N(CCC2CC2)c2cc3[nH]c(N)nc3cc21
null
[NH2:1][C:2]1[NH:3][C:4]2[C:5]([N:21]=1)=[CH:6][C:7]1[C:8]([CH3:20])([CH3:19])[C:9](=[O:18])[N:10]([CH2:13][CH2:14][CH:15]3[CH2:17][CH2:16]3)[C:11]=1[CH:12]=2.[C:22](Cl)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CCN(CC)CC>C1COCC1.C(Cl)Cl>[CH:15]1([CH2:14][CH2:13][N:10]2[C:11]3[CH:12]=[C:4]4[NH:3][C:2]([NH:1][C:22](=[O:29])[C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)=[N:21][C:5]4=[CH:6][C:7]=3[C:8]([CH3:19])([CH3:20])[C:9]2=[O:18])[CH2:17][CH2:16]1
null
ClCCl
CCN(CC)CC
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
545,567
null
null
null
null
ord_dataset-d31180f42ced44719fd9e72685c798bf
2002-01-01T00:05:00
true
Trifluoroacetic acid (4 mL) is added to a stirred, cooled (0° C.) solution of (2S)- 1-tert-butoxycarbonyl-2-phenylpiperidin-3-one (40 mg) in methylene chloride (2 mL) and the mixture is stirred at room temperature for 3 h. The solvent is evaporated under reduced pressure and the residue is partitioned between aqueous saturated sodium bicarbonate (50 ml) and ethyl acetate (3×50 ml). The combined organic fractions are washed with brine (50 ml), dried (MgSO4) and evaporated in vacuo to give (2S)-2-phenylpiperidin-3-one.
O=C1CCCN[C@H]1c1ccccc1
null
CC(C)(C)OC(=O)N1CCCC(=O)[C@@H]1c1ccccc1
null
null
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:20][CH2:19][CH2:18][C:17](=[O:21])[C@@H:16]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=O)(C)(C)C>C(Cl)Cl>[C:22]1([C@H:16]2[C:17](=[O:21])[CH2:18][CH2:19][CH2:20][NH:15]2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
3
ClCCl
O=C(O)C(F)(F)F
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
1,119,919
[Li]CCCC
null
null
null
ord_dataset-4226e9b4f9f845db967ed997270dcafc
2011-01-01T00:12:00
true
To a −60° C. solution of n-butyl lithium (23 mL, 2.5M in hexane, 58.2 mmol) in diethyl ether (40 mL) was added a solution of 2-bromo-3-chloropyridine (Alfa, 8.0 g, 41.6 mmol) in diethyl ether (60 mL) over 15 minutes. The reaction mixture was stirred for 40 minutes followed by a slow addition (about 15 minutes) of a solution of 1,4-dioxaspiro[4.5]decan-8-one (Aldrich, 8.44 g, 54.0 mmol) in diethyl ether (100 mL), and stirred until reaction mixture warmed up to ambient temperature (about 3 hours). The mixture was quenched with saturated NH4Cl, diluted with ethyl acetate and washed with water. The organic layer was separated, concentrated and the residue crystallized from ethyl acetate-hexanes to obtain 5.5 g of the title compound. Two more crystallizations of the mother liquors yielded 1.61 g more material. Total yield 7.13 g (64%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.59 (d, J=12.69 Hz, 2H), 1.80 (d, J=12.69 Hz, 2H), 1.94 (td, J=12.69, 4.36 Hz, 2H), 2.30-2.41 (m, 2H), 3.88 (s, 4H), 5.36 (s, 1H), 7.36 (dd, J=7.93, 4.76 Hz, 1H), 7.88 (dd, J=7.93, 1.59 Hz, 1H), 8.48 (dd, J=4.76, 1.59 Hz, 1H). MS (DCI) m/z 270.10 (M+H)+.
OC1(c2ncccc2Cl)CCC2(CC1)OCCO2
null
Clc1cccnc1Br
O=C1CCC2(CC1)OCCO2
null
C([Li])CCC.Br[C:7]1[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][N:8]=1.[O:14]1[C:18]2([CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]2)[O:17][CH2:16][CH2:15]1>C(OCC)C>[Cl:13][C:12]1[C:7]([C:21]2([OH:24])[CH2:22][CH2:23][C:18]3([O:17][CH2:16][CH2:15][O:14]3)[CH2:19][CH2:20]2)=[N:8][CH:9]=[CH:10][CH:11]=1
0.67
CCOCC
null
null
25
49
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
939,119
[Na+]
[OH-]
null
null
ord_dataset-90b0aa1f83334a02919b2be3a1c04542
2010-01-01T00:02:00
true
A solution of N-(4-(4H-1,2,4-triazol-3-yl)phenethyl)-2,2,2-trifluoroacetamide (83 mg, 0.292 mmol) and NaOH (29 mg, 0.73 mmol) in a mixed solvent (THF/MeOH/H2O=2 mL/5 mL/1 mL) was stirred at RT for 2 h. The solvent was evaporated to dryness and the residue was submitted to flash chomatography (SiO2, EtOAc to EtOAc/2M NH3 in MeOH=100:20 to 100:50) to give 2-(4-(4H-1,2,4-triazol-3-yl)phenyl)-ethanamine as a colorless oil.
NCCc1ccc(-c2nnc[nH]2)cc1
null
O=C(NCCc1ccc(-c2nnc[nH]2)cc1)C(F)(F)F
null
null
[N:1]1[N:2]=[C:3]([C:6]2[CH:20]=[CH:19][C:9]([CH2:10][CH2:11][NH:12]C(=O)C(F)(F)F)=[CH:8][CH:7]=2)[NH:4][CH:5]=1.[OH-].[Na+]>C1COCC1.CO.O>[N:1]1[N:2]=[C:3]([C:6]2[CH:7]=[CH:8][C:9]([CH2:10][CH2:11][NH2:12])=[CH:19][CH:20]=2)[NH:4][CH:5]=1
null
C1CCOC1
CO
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
1,464,354
N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
O=C([O-])O
[Na+]
null
ord_dataset-fd1fa959d6264608b0b7fcda16741bfd
2014-01-01T00:08:00
true
159 mg (0.29 mmol) of tert-butyl 3-{3-[bis(4-methoxybenzyl)amino]-4-chlorophenyl}-3-(1-methylcyclopropyl)propanoate were taken up in 7 ml of dichloromethane and 1.2 ml of water. 145 mg (0.64 mmol) of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) were then added, and the reaction solution was stirred at room temperature for 2 h. The reaction mixture was then added to 10 ml of saturated aqueous sodium bicarbonate solution. The phases were separated, and the aqueous phase was then extracted three more times with in each case about 10 ml of dichloromethane. The combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. The product was isolated from the residue by preparative RP-HPLC (mobile phase methanol/water). This gave 31 mg of the target product (34% of theory).
CC(C)(C)OC(=O)CC(c1ccc(Cl)c(N)c1)C1(C)CC1
null
COc1ccc(CN(Cc2ccc(OC)cc2)c2cc(C(CC(=O)OC(C)(C)C)C3(C)CC3)ccc2Cl)cc1
null
null
COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[CH:10]=[C:11]([CH:16]([C:25]3([CH3:28])[CH2:27][CH2:26]3)[CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:12]=[CH:13][C:14]=2[Cl:15])=CC=1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.C(=O)(O)[O-].[Na+]>ClCCl.O>[NH2:8][C:9]1[CH:10]=[C:11]([CH:16]([C:25]2([CH3:28])[CH2:26][CH2:27]2)[CH2:17][C:18]([O:20][C:21]([CH3:23])([CH3:24])[CH3:22])=[O:19])[CH:12]=[CH:13][C:14]=1[Cl:15]
2
ClCCl
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
112,177
null
null
null
null
ord_dataset-5237a168f9214b7ca3db5a1dc3e62d07
1983-01-01T00:12:00
true
To 10 ml of an ethereal solution of 425 mg of α-bromomethyl-2,4-dichlorobenzyl alcohol and 340 mg of 2-(2,4-dichlorophenoxymethyl)-3,4-dihydro-2H-pyran was added a catalytic amount (2 drops) of phosphorus oxytrichloride, and the mixture was stirred at room temperature for 4 days. 3 drops of triethylamine were then added and the solvent was evaporated off under reduced pressure. The residue was purified by column chromatography through silica gel eluted with a 40:2:1 by volume mixture of hexane, benzene and ethyl acetate, to give 681 mg of the isomer of lesser polarity of trans-6-(2,4-dichlorophenoxymethyl)-2-[2-bromo-1-(2,4-dichlorophenyl)ethoxy]tetrahydropyran as colorless crystals melting at 104°-105° C.
Clc1ccc(OC[C@H]2CCC[C@H](OC(CBr)c3ccc(Cl)cc3Cl)O2)c(Cl)c1
null
OC(CBr)c1ccc(Cl)cc1Cl
Clc1ccc(OCC2CCC=CO2)c(Cl)c1
null
[Br:1][CH2:2][CH:3]([OH:12])[C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][C:5]=1[Cl:11].[Cl:13][C:14]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:15]=1[O:16][CH2:17][CH:18]1[CH2:23][CH2:22][CH:21]=[CH:20][O:19]1>O=P(Cl)(Cl)Cl.C(N(CC)CC)C>[Cl:13][C:14]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:15]=1[O:16][CH2:17][C@@H:18]1[O:19][C@@H:20]([O:12][CH:3]([C:4]2[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][C:5]=2[Cl:11])[CH2:2][Br:1])[CH2:21][CH2:22][CH2:23]1
96
CCN(CC)CC
O=P(Cl)(Cl)Cl
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
514,742
null
null
null
null
ord_dataset-41760195182e4bb4bc779bd722456071
2001-01-01T00:08:00
true
To a solution of ethyl 3-(3,4-methylenedioxyphenyl)-1-oxoindene-2-carboxylate (100 mg, 0.31 mmol) in THF (5 ml) under an argon atmosphere at 0° C. was added a solution of freshly prepared 4-fluorophenyl magnesium bromide (0.62 mmol). After stirring for 45 min, the mixture was partitioned between 3M HCl and EtOAc. The organic extract was washed successively with H2O, 5% aqueous NaHCO3 and saturated aqueous NaCl. The solvent was removed in vacua, and the residue was purified by flash chromatography, eluting with 15% EtOAc/hexanes to afford the title compound (45 mg, 35%).
O=C(O)C1C(c2ccc(F)cc2)c2ccccc2C1c1ccc2c(c1)OCO2
null
CCOC(=O)C1=C(c2ccc3c(c2)OCO3)c2ccccc2C1=O
Fc1ccc([Mg]Br)cc1
null
[CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[C:12](=O)[C:11]=3[C:20]([O:22]CC)=[O:21])=[CH:4][C:3]=2[O:2]1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([Mg]Br)=[CH:28][CH:27]=1>C1COCC1>[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:10]([C:5]3[CH:6]=[CH:7][C:8]4[O:9][CH2:1][O:2][C:3]=4[CH:4]=3)[CH:11]2[C:20]([OH:22])=[O:21])=[CH:28][CH:27]=1
0.75
C1CCOC1
null
null
null
38.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
361,101
[H-]
[Na+]
null
null
ord_dataset-0b24d1f58a024ed7bc2bda95b2430c72
1997-01-01T00:04:00
true
A solution of 0.55 g (4.54 mmol) of 2-methylpyridine-5-carboxaldehyde in toluene was added dropwise into a cool suspension of 1.12 g (5 mmol) of ethyl diethylphosphonoacetate and 0.12 g (5 mmol) of NaH in toluene and the resulting solution was allowed to react at 65° C. for 30 min. After cooling, the mixture was filtered through SUPERCEL™ (wash SUPERCEL™ with ether) and concentrated in vacuo to yield 0.71 g (87.6%) of ethyl β-(2-methylpyridin-3-yl)acrylate (cis/trans mixture), which was further purified through a silica plug (hexane/ethyl acetate, 1:1).
CCOC(=O)C=Cc1cccnc1C
null
Cc1ccccc1
Cc1ccc(C=O)cn1
CCOC(=O)CP(=O)(OCC)OCC
C[C:2]1[CH:7]=[CH:6][C:5]([CH:8]=O)=[CH:4][N:3]=1.C(OP([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])(OCC)=O)C.[H-].[Na+].[C:26]1(C)C=CC=CC=1>>[CH3:26][C:4]1[C:5]([CH:8]=[CH:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:6][CH:7]=[CH:2][N:3]=1
null
null
null
null
null
87.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,500,178
CC(C)(C)[O-]
CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1
[Na+]
null
ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2
2014-01-01T00:10:00
true
To a solution of -(4-chloro-1,6-naphthyridin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (300 mg, 0.84 mmol, prepared in analogy to 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide in Example 2-1 by using 2,3,4,5-tetrahydro-1,4-benzothiazepine and 2,4-dichloro-1,6-naphthyridine) in 1,4-dioxane (5 mL) was added tert-butyl (trans-4-hydroxypyrrolidin-3-yl)carbamate (204 mg, 1.02 mmol), tri(dibenzylideneacetone)dipalladium(0) (39 mg, 0.042 mmol), (2′-dicyclohexylphosphanyl-biphenyl-2-yl)-dimethyl-amine (24 mg, 0.063 mmol) and sodium tert-butoxide (114 mg, 1.17 mmol) under Ar protection. The reaction mixture was heated with stirring in a 10 mL of microwave process vial for 2 hours at 120° C. The reaction mixture was concentrated in vacuo. The residue was purified by preparative HPLC to give 45 mg of the desired product (yield was 10%).
CC(C)(C)OC(=O)N[C@@H]1CN(c2cc(N3CCS(=O)(=O)c4ccccc4C3)nc3ccncc23)C[C@H]1O
null
Cc1ccc2nc(N3CCS(=O)(=O)c4ccccc4C3)cc(NCC3(N(Cc4ccccc4)Cc4ccccc4)CCOC3)c2c1
CC(C)(C)OC(=O)N[C@@H]1CNC[C@H]1O
null
C(N(CC1C=CC=CC=1)[C:9]1([CH2:14][NH:15][C:16]2[C:25]3[C:20](=CC=C(C)[CH:24]=3)[N:19]=[C:18]([N:27]3[CH2:33][C:32]4[CH:34]=[CH:35][CH:36]=[CH:37][C:31]=4[S:30](=[O:39])(=[O:38])[CH2:29][CH2:28]3)[CH:17]=2)CCOC1)C1C=CC=CC=1.[OH:47][C@@H:48]1[CH2:52][NH:51][CH2:50][C@H:49]1[NH:53][C:54](=[O:60])[O:55][C:56]([CH3:59])([CH3:58])[CH3:57].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.CC(C)([O-])C.[Na+]>O1CCOCC1>[O:38]=[S:30]1(=[O:39])[C:31]2[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=2[CH2:33][N:27]([C:18]2[CH:17]=[C:24]([N:51]3[CH2:50][C@@H:49]([NH:53][C:54]([O:55][C:56]([CH3:57])([CH3:59])[CH3:58])=[O:60])[C@H:48]([OH:47])[CH2:52]3)[C:25]3[C:20](=[CH:9][CH:14]=[N:15][CH:16]=3)[N:19]=2)[CH2:28][CH2:29]1
2
C1COCCO1
null
null
120
null
10.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,535,667
null
null
null
null
ord_dataset-8d5c200bca27407ab9febe7598e16458
2015-01-01T00:01:00
true
To (E)-(2S,3S,4S,5S)-3,5-Dimethoxy-2,4-dimethyl-oct-6-en-1-ol (1.5 g, 6.94 mmol) in anhydrous pyridine (20 ml) at 0° C. and under an atmosphere of nitrogen was added pivaloyl chloride (1.33 ml, 10.7 mmol). The reaction was warmed to room temperature and stirred for 2 hours, after which it was quenched with saturated ammonium chloride and extracted with dichloromethane (2×). The combined organic layers were dried by passing through a hydrophobic frit and concentrated in vacuo. The product was purified by flash chromatography (SiO2, iHex/EtOAc, 20:1 then 1:1) to afford 2.0 g (100%) as a clear oil. 1H NMR (300 MHz, CDCl3) δ 5.67 (dq, J=15.3 Hz, 6.6 Hz, 1H), 5.21 (m, 1H), 4.23 (dd, J=10.6 Hz, 3.3 Hz, 1H), 4.1 (dd, J=10.6 Hz, 6.0 Hz, 1H), 3.52 (dd, J=10.0 Hz, 2.0 Hz, 1H), 3.42 (s, 3H), 3.34 (t, J=9.3 Hz, 1H), 3.25 (s, 3H), 1.96 (m, 1H), 1.78 (dd, J=6.4 Hz, 1.5 Hz, 3H), 1.68 (m, 1H), 1.24 (s, 9H), 0.90 (d, J=7.1 Hz, 3H), 0.76 (d, J=7.1 Hz, 3H).
C/C=C/[C@H](OC)[C@H](C)[C@@H](OC)[C@@H](C)COC(=O)C(C)(C)C
null
C/C=C/[C@H](OC)[C@H](C)[C@@H](OC)[C@@H](C)CO
CC(C)(C)C(=O)Cl
null
[CH3:1][O:2][C@H:3]([C@@H:8]([CH3:15])[C@@H:9]([O:13][CH3:14])/[CH:10]=[CH:11]/[CH3:12])[C@@H:4]([CH3:7])[CH2:5][OH:6].[C:16](Cl)(=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18]>N1C=CC=CC=1>[CH3:1][O:2][C@H:3]([C@@H:8]([CH3:15])[C@@H:9]([O:13][CH3:14])/[CH:10]=[CH:11]/[CH3:12])[C@@H:4]([CH3:7])[CH2:5][O:6][C:16](=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18]
2
c1ccncc1
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
500,992
null
null
null
null
ord_dataset-d673d02cdac14dba9ff59f12845a4f37
2001-01-01T00:05:00
true
Using an analogous procedure to that described in Example 14, 1-(4-pyridyl)piperazine was reacted with 1-(2-naphthylsulphonyl)piperidine-3-carboxylic acid to give 1-[1-(2-naphthylsulphonyl)-piperidin-3-ylcarbonyl]-4-(4-pyridyl)piperazine as a foam in 25% yield;
O=C(C1CCCN(S(=O)(=O)c2ccc3ccccc3c2)C1)N1CCN(c2ccncc2)CC1
null
O=C(O)C1CCCN(S(=O)(=O)c2ccc3ccccc3c2)C1
c1cc(N2CCNCC2)ccn1
null
[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:3][CH:2]=1.[CH:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][C:14]=1[S:23]([N:26]1[CH2:31][CH2:30][CH2:29][CH:28]([C:32](O)=[O:33])[CH2:27]1)(=[O:25])=[O:24]>>[CH:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][C:14]=1[S:23]([N:26]1[CH2:31][CH2:30][CH2:29][CH:28]([C:32]([N:10]2[CH2:9][CH2:8][N:7]([C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)[CH2:12][CH2:11]2)=[O:33])[CH2:27]1)(=[O:24])=[O:25]
null
null
null
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
783,690
null
null
null
null
ord_dataset-4ad5db8537994579bef51f16dd8bf0bd
2007-01-01T00:08:00
true
The title compound is prepared from a mixture of (R)-6-fluoro-3-(4-oxiranylmethoxy-phenyl)-benzo[d]isoxazole in dimethylformamide and 4-(3-chlorophenoxy)-piperidine (Table No.1, SM 7) in ethanol, essentially as described above in Example 70. Purity by LC/MS=100%, [M+H]+=497.
O[C@@H](COc1ccc(-c2noc3cc(F)ccc23)cc1)CN1CCC(Oc2cccc(Cl)c2)CC1
null
Fc1ccc2c(-c3ccc(OC[C@H]4CO4)cc3)noc2c1
Clc1cccc(OC2CCNCC2)c1
null
[F:1][C:2]1[CH:21]=[CH:20][C:5]2[C:6]([C:9]3[CH:14]=[CH:13][C:12]([O:15][CH2:16][C@H:17]4[CH2:19][O:18]4)=[CH:11][CH:10]=3)=[N:7][O:8][C:4]=2[CH:3]=1.[Cl:22][C:23]1[CH:24]=[C:25]([CH:33]=[CH:34][CH:35]=1)[O:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1>CN(C)C=O.C(O)C>[Cl:22][C:23]1[CH:24]=[C:25]([CH:33]=[CH:34][CH:35]=1)[O:26][CH:27]1[CH2:28][CH2:29][N:30]([CH2:19][C@@H:17]([OH:18])[CH2:16][O:15][C:12]2[CH:11]=[CH:10][C:9]([C:6]3[C:5]4[CH:20]=[CH:21][C:2]([F:1])=[CH:3][C:4]=4[O:8][N:7]=3)=[CH:14][CH:13]=2)[CH2:31][CH2:32]1
null
CCO
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
1,355,768
[K+]
[OH-]
null
null
ord_dataset-6034127657614f02860ed057b62b882e
2013-01-01T00:10:00
true
2-(2-Cyclopentyl-2-phenyl-acetylamino)-indan-2-carboxylic acid ethyl ester (268) (1 g, 2.56 mmol) is dissolved in EtOH (50 mL) and set to stir at RT. To this solution is added 5M KOH (3 ml). The reaction mixture is stirred at RT overnight. After concentration in vacuo, the residue is dissolved in water (20 mL) and washed with EtOAc (20 ml). The phases are separated and the aqueous phase is acidified with concentrated HCl to pH 2. The solid precipitate is collected via filtration and dried under vacuum. The desired product (269) is obtained as white solid (710 mg, 71%).
O=C(NC1(C(=O)O)Cc2ccccc2C1)C(c1ccccc1)C1CCCC1
null
CCOC(=O)C1(NC(=O)C(c2ccccc2)C2CCCC2)Cc2ccccc2C1
null
null
C([O:3][C:4]([C:6]1([NH:15][C:16](=[O:29])[CH:17]([CH:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])C.[OH-].[K+]>CCO>[CH:24]1([CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:16]([NH:15][C:6]2([C:4]([OH:5])=[O:3])[CH2:7][C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH2:14]2)=[O:29])[CH2:28][CH2:27][CH2:26][CH2:25]1
null
CCO
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
1,150,423
CN(C)C(On1nnc2cccnc21)=[N+](C)C
F[P-](F)(F)(F)(F)F
null
null
ord_dataset-b195433d5c354ddfb6cde0d53c41910f
2012-01-01T00:04:00
true
DIEA (51 μL, 0.293 mmol) was added to a stirring solution of 3-(3-(ethoxycarbonyl)-2-(4-fluorophenyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)benzoic acid (50 mg, 0.098 mmol), 2-phenylpropan-2-amine (26 mg, 0.195 mmol), HATU (56 mg, 0.147 mmol) in DMF (1 mL) at 25° C. It was allowed to stir for 1 hour. The mixture was diluted with EtOAc and washed with 1M HCl, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated to give the titled compound (50 mg, 81%). LC-MS retention time: 1.82 min; m/z (MH+): 629. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.
CCOC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3cccc(C(=O)NC(C)(C)c4ccccc4)c3)cc12
null
CC(C)(N)c1ccccc1
CCOC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3cccc(C(=O)O)c3)cc12
null
CCN(C(C)C)C(C)C.[CH2:10]([O:12][C:13]([C:15]1[C:19]2[CH:20]=[C:21]([C:30]3[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=3)[C:33]([OH:35])=O)[C:22]([N:24]([CH3:29])[S:25]([CH3:28])(=[O:27])=[O:26])=[CH:23][C:18]=2[O:17][C:16]=1[C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=1)=[O:14])[CH3:11].[C:46]1([C:52]([NH2:55])([CH3:54])[CH3:53])[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[F:45][C:42]1[CH:41]=[CH:40][C:39]([C:16]2[O:17][C:18]3[CH:23]=[C:22]([N:24]([CH3:29])[S:25]([CH3:28])(=[O:27])=[O:26])[C:21]([C:30]4[CH:38]=[CH:37][CH:36]=[C:32]([C:33](=[O:35])[NH:55][C:52]([C:46]5[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=5)([CH3:54])[CH3:53])[CH:31]=4)=[CH:20][C:19]=3[C:15]=2[C:13]([O:12][CH2:10][CH3:11])=[O:14])=[CH:44][CH:43]=1
1
CCOC(C)=O
CN(C)C=O
CCN(C(C)C)C(C)C
null
null
81.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,458,166
[NH4+]
[OH-]
null
null
ord_dataset-a86112d52cd54525a5e36d41f18aced2
2014-01-01T00:07:00
true
tert-Butyl cis-3-(7-(5-methoxy-1-methyl-1H-indol-3-yl)-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)cyclopentylcarbamate (0.331 g, 0.524 mmol, prepared using J.1 from Preparation #I.1 with cis-3-(tert-butoxycarbonylamino)cyclopentanecarboxylic acid [Peptech], and L.1 with mercury(II) trifluoroacetate) in DCM (8 mL) was treated with TFA (2.0 mL, 26 mmol) then stirred for about 1.5 h at rt. The solvents were removed under reduced pressure then the material was dissolved in 1,4-dioxane (4 mL) and treated with concentrated aqueous NH4OH (2.5 mL, 24 mmol). The mixture was heated at about 60° C. for about 30 min. The mixture was concentrated under reduced pressure then dissolved in AcOH (1 mL) and DMF (3.5 mL) then the material was purified by preparative reverse phase HPLC (Table 2, Method i) to give cis-3-(7-(5-methoxy-1-methyl-1H-indol-3-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)cyclopentanamine diacetate (0.145 g, 53%): LC/MS (Table 2, Method a) Rt=1.73 min; MS m/z 401.2 (M+H)+. Syk IC50=A.
CC(=O)O
COc1ccc2c(c1)c(-c1cc3c(ncc4cnc([C@@H]5CC[C@H](N)C5)n43)[nH]1)cn2C
COc1ccc2c(c1)c(-c1cc3c(ncc4cnc([C@@H]5CC[C@H](NC(=O)OC(C)(C)C)C5)n43)n1COCC[Si](C)(C)C)cn2C
O=C(O)C(F)(F)F
null
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[N:37](COCC[Si](C)(C)C)[C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([C@@H:24]4[CH2:28][CH2:27][C@H:26]([NH:29]C(=O)OC(C)(C)C)[CH2:25]4)=[N:22][CH:23]=3)[C:15]=2[CH:14]=1.[C:46]([OH:52])([C:48](F)(F)F)=[O:47].[NH4+].[OH-]>C(Cl)Cl>[C:46]([OH:52])(=[O:47])[CH3:48].[C:46]([OH:52])(=[O:47])[CH3:48].[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[NH:37][C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([C@@H:24]4[CH2:28][CH2:27][C@H:26]([NH2:29])[CH2:25]4)=[N:22][CH:23]=3)[C:15]=2[CH:14]=1
1.5
ClCCl
null
null
25
null
53.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,256,829
null
null
null
null
ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0
2013-01-01T00:02:00
true
The title compound was prepared from rac-[(3,4-dichloro-phenyl)-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid tert-butyl ester (Intermediate 9) and rac-5-bromo-3-methyl-2-(tetrahydro-furan-3-yloxy)-pyridine (Intermediate 29) in analogy to Example 1a): MS (ISP): 481.3 and 483.2 (M+H)+.
Cc1cc(C(=O)C(NC(=O)OC(C)(C)C)c2ccc(Cl)c(Cl)c2)cnc1OC1CCOC1
null
Cc1cc(Br)cnc1OC1CCOC1
CON(C)C(=O)C(NC(=O)OC(C)(C)C)c1ccc(Cl)c(Cl)c1
null
[C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=1)[C:9](=[O:14])N(OC)C)([CH3:4])([CH3:3])[CH3:2].Br[C:25]1[CH:26]=[C:27]([CH3:37])[C:28]([O:31][CH:32]2[CH2:36][CH2:35][O:34][CH2:33]2)=[N:29][CH:30]=1>>[C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=1)[C:9]([C:25]1[CH:30]=[N:29][C:28]([O:31][CH:32]2[CH2:36][CH2:35][O:34][CH2:33]2)=[C:27]([CH3:37])[CH:26]=1)=[O:14])([CH3:2])([CH3:3])[CH3:4]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,353,974
null
null
null
null
ord_dataset-6034127657614f02860ed057b62b882e
2013-01-01T00:10:00
true
The title compound was prepared from 2,2-dimethyl-3-((R)-2-oxo-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-6-yl)propanenitrile and 2-bromo-N-tert-butylthiazole-5-carboxamide following a procedure analogous to that described in Example 1 Step 2. LC-MS Method 2 tR=1.292 min, m/z=545.4; 1H NMR (CDCl3) 1.25 (s, 3H), 1.40 (s, 3H), 1.49 (d, 3H), 2.11 (s, 2H), 2.26 (m, 1H), 2.42 (m, 2H), 2.88 (m, 1H), 5.61 (m, 1H), 5.73 (s, 1H), 6.85 (m, 2H), 7.31 (m, 5H), 7.60 (m, 2H), 8.00 (m, 1H).
C[C@@H](c1ccc(-c2ncc(C(=O)NC(C)(C)C)s2)cc1)N1CC[C@](CC(C)(C)C#N)(c2ccccc2)OC1=O
null
CC(C)(C)NC(=O)c1cnc(Br)s1
C[C@@H](c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)N1CC[C@](CC(C)(C)C#N)(c2ccccc2)OC1=O
null
[CH3:1][C:2]([CH3:36])([CH2:5][C@@:6]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[O:11][C:10](=[O:12])[N:9]([C@H:13]([C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[CH:17][CH:16]=2)[CH3:14])[CH2:8][CH2:7]1)[C:3]#[N:4].Br[C:38]1[S:39][C:40]([C:43]([NH:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[CH:41][N:42]=1>>[C:46]([NH:45][C:43]([C:40]1[S:39][C:38]([C:18]2[CH:19]=[CH:20][C:15]([C@@H:13]([N:9]3[CH2:8][CH2:7][C@:6]([CH2:5][C:2]([C:3]#[N:4])([CH3:36])[CH3:1])([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)[O:11][C:10]3=[O:12])[CH3:14])=[CH:16][CH:17]=2)=[N:42][CH:41]=1)=[O:44])([CH3:49])([CH3:47])[CH3:48]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,690,092
O=C([O-])O
[Na+]
null
null
ord_dataset-c1e70ad912eb438f8d34b1dc681f809a
2016-01-01T00:02:00
true
TFA (2 mL) was added to a solution of tert-butyl 2-((2-oxo-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-1(2H)-yl)methyl)-1H-indole-1-carboxylate (130 mg, 0.32 mmol) in dichloromethane (3 mL) at 20° C. The mixture was stirred at room temperature for 2 hours. LC-MS showed the tert-butyl 2-((2-oxo-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-1(2H)-yl)methyl)-1H-indole-1-carboxylate had disappeared. The reaction mixture was adjusted to a pH of around 8-9 with saturated NaHCO3 solution, extracted with dichloromethane, and dried with Na2SO4. The organic phase was evaporated, and the residue was purified with prep-HPLC (A: H2O including 0.5% NH3HCO3, B: CH3CN) to afford 1-((1H-indol-2-yl)methyl)-4-(2-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-4-yl)pyridin-2(1H)-one (60 mg, 60% yield). 1H NMR (500 MHz, (CD3)2SO) δ 11.07 (s, 1H), 8.41 (d, J=4.5 Hz, 1H), 7.88 (d, J=7.5 Hz, 1H), 7.47 (d, J=8 Hz, 1H), 7.37-7.36 (m, 2H), 7.15-7.14 (m, 2H), 7.06 (m 1H), 6.96 (m, 1H), 6.88 (d, J=6 Hz, 1H), 6.35 (s, 1H), 5.26 (s, 2H), 3.97 (m, 1H), 3.88-3.86 (m, 2H), 3.42-3.37 (m, 2H), 1.85-1.83 (m, 2H), 1.56-1.48 (m, 2H); LCMS (ESI) m/z 402.3 [M+H+].
O=c1cc(-c2ccnc(NC3CCOCC3)n2)ccn1Cc1cc2ccccc2[nH]1
null
CC(C)(C)OC(=O)n1c(Cn2ccc(-c3ccnc(NC4CCOCC4)n3)cc2=O)cc2ccccc21
null
null
C(O)(C(F)(F)F)=O.[O:8]=[C:9]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([NH:21][CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[N:16]=2)[CH:12]=[CH:11][N:10]1[CH2:28][C:29]1[N:30](C(OC(C)(C)C)=O)[C:31]2[C:36]([CH:37]=1)=[CH:35][CH:34]=[CH:33][CH:32]=2.C([O-])(O)=O.[Na+].CC#N>ClCCl>[NH:30]1[C:31]2[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:37]=[C:29]1[CH2:28][N:10]1[CH:11]=[CH:12][C:13]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([NH:21][CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[N:16]=2)=[CH:14][C:9]1=[O:8]
2
CC#N
ClCCl
O=C(O)C(F)(F)F
25
null
46.7
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
481,312
O=C([O-])[O-]
[K+]
null
null
ord_dataset-21c1b1c06c7e4e09a38b5b1c71a32e52
2000-01-01T00:10:00
true
A reaction vessel was charged with 0.35 g of 3,5-diethyl-4-(4-(3,3-dichloro-2-propenyloxy)butyloxy)phenol, 0.16 g of 1,1,3-trichloro-1-propene, 0.15 g of potassium carbonate and 10 ml of N,N-dimethylformamide. After stirring at room temperature for 24 hours, the reaction mixture was poured into water and extracted twice with 50 ml of diethyl ether. The diethyl ether layers were combined, washed with water, dried over magnesium sulfate and then concentrated. The residue was subjected to silica gel chromatography, which afforded 0.33 g of 3,5-diethyl-1-(3,3-dichloro-2-propenyloxy)-4-(4-(3,3-dichloro-2-propenyloxy)butyloxy)benzene (yield, 72%), nD24.4 1.5311.
CCc1cc(OCC=C(Cl)Cl)cc(CC)c1OCCCCOCC=C(Cl)Cl
null
CCc1cc(O)cc(CC)c1OCCCCOCC=C(Cl)Cl
ClCC=C(Cl)Cl
null
[CH2:1]([C:3]1[CH:4]=[C:5]([OH:22])[CH:6]=[C:7]([CH2:20][CH3:21])[C:8]=1[O:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][CH2:15][CH:16]=[C:17]([Cl:19])[Cl:18])[CH3:2].[Cl:23][C:24]([Cl:28])=[CH:25][CH2:26]Cl.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH2:20]([C:7]1[CH:6]=[C:5]([O:22][CH2:26][CH:25]=[C:24]([Cl:28])[Cl:23])[CH:4]=[C:3]([CH2:1][CH3:2])[C:8]=1[O:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][CH2:15][CH:16]=[C:17]([Cl:19])[Cl:18])[CH3:21]
24
O
CN(C)C=O
null
25
71.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
398,541
null
null
null
null
ord_dataset-a4a191e812a64d0598ea918f047e8da7
1998-01-01T00:04:00
true
To a stirred suspension of diethyl 6-nitro-4-hydroxy-quinoline-2,3-dicarboxylate (1.670 g, 5.00 mM) in ethanol (30 mL) was added phenyl hydrazine (3.44 mL, 35.00 mM) to give a deep red solution. The solution was heated to reflux for 1 hour and concentrated to about 15 mL. Continued heating gave a thick suspension which was diluted with ethanol (5 mL) and refluxed for 16 additional hours. The mixture was cooled to room temperature and filtered to give thephenyl hydrazine salt of the title compound as a tan solid. This material was refluxed in glacial acetic acid (25 mL) for 2 hours and cooled to roomtemperature. Filtration gave the title compound (1.01 g, 58%) as a tan powder, mp 368° C. (decomp.); MS(CI): 351 (M+H). Analysis for C17H10N4O5 : Calculated: C, 58.30; H, 2.88; N, 16.00; Found: C, 58.21; H, 3.07; N, 16.15; NMR: 8.91 (d, J=2.76 Hz, 1H), 8.60 (dd, J=2.76, 9.18 Hz, 1H), 8.06 (d, J=9.18 Hz, 1H,), 7.18 (t, J=7.23 Hz, 2H), 6.82 (m, 3H).
NN
O=c1c2cc([N+](=O)[O-])ccc2[nH]c2c(O)nn(-c3ccccc3)c(=O)c12
CCOC(=O)c1nc2ccc([N+](=O)[O-])cc2c(O)c1C(=O)OCC
NNc1ccccc1
null
[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[C:9]([C:14]([O:16]CC)=O)[C:8]([C:19]([O:21]CC)=O)=[C:7]2[OH:24])([O-:3])=[O:2].[C:25]1([NH:31][NH2:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C(O)C>[NH2:31][NH2:32].[OH:16][C:14]1[C:9]2[NH:10][C:11]3[CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]=3[C:7](=[O:24])[C:8]=2[C:19](=[O:21])[N:31]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:32]=1
null
CCO
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
274,543
null
null
null
null
ord_dataset-ee287d49cb8642e59ae9c3951f746312
1993-01-01T00:08:00
true
A mixture consisting of 4-(4-cyclohexylphenyl)-2-ethoxymethyleneaminothiazole (500 mg), ethyl carbazate (170 mg) and ethanol (10 ml) was stirred under ice-cooling for 1 hour and then at room temperature (about 15° C.) for 18 hours. The reaction mixture was concentrated under reduced pressure, and the crystals were collected by filtration with hexane to give ethyl 3-[4-(4-cyclohexylphenyl)-2-thiazolyliminomethyl]carbazate (515 mg, yield of 87 %). Recrystallization from dimethylforamide-water produced colorless prisms, mp of 188 to 189° C.
CCOC(=O)NNC=Nc1nc(-c2ccc(C3CCCCC3)cc2)cs1
null
CCOC(=O)NN
CCOC=Nc1nc(-c2ccc(C3CCCCC3)cc2)cs1
null
[CH:1]1([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[N:14]=[C:15]([N:18]=[CH:19]OCC)[S:16][CH:17]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:23]([O:27][CH2:28][CH3:29])(=[O:26])[NH:24][NH2:25]>C(O)C>[CH:1]1([C:7]2[CH:8]=[CH:9][C:10]([C:13]3[N:14]=[C:15]([N:18]=[CH:19][NH:25][NH:24][C:23]([O:27][CH2:28][CH3:29])=[O:26])[S:16][CH:17]=3)=[CH:11][CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
18
CCO
null
null
null
null
87
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
982,270
null
null
null
null
ord_dataset-35b56288528641309a040cc2b6710b61
2010-01-01T00:08:00
true
400 mg of tert-butyl 5-cyclopropyl-1,1-dioxo-[1,2,5]thiadiazolidine-2-carboxylate were dissolved in 10 ml of CH2Cl2/trifluoroacetic acid 1:1 and left to stand for 2 hours. The volatile constituents were removed in vacuo and coevaporated twice with 50 ml of CH2Cl2 each time. 410 mg of pale yellow oil were obtained and were directly employed further.
O=S1(=O)NCCN1C1CC1
null
CC(C)(C)OC(=O)N1CCN(C2CC2)S1(=O)=O
null
null
[CH:1]1([N:4]2[S:8](=[O:10])(=[O:9])[N:7](C(OC(C)(C)C)=O)[CH2:6][CH2:5]2)[CH2:3][CH2:2]1>C(Cl)Cl.FC(F)(F)C(O)=O>[CH:1]1([N:4]2[CH2:5][CH2:6][NH:7][S:8]2(=[O:10])=[O:9])[CH2:3][CH2:2]1
2
O=C(O)C(F)(F)F
ClCCl
null
null
null
165.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
911,085
null
null
null
null
ord_dataset-c663259b80f947e2a8923796fb0e9a6b
2009-01-01T00:10:00
true
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-methoxyaniline (30 mg) was dissolved in chloroform (1 ml) and triethylamine (0.1 ml) to prepare a solution. A solution of triphosgene (35 mg) in chloroform (0.2 ml) was then added to the solution, and the mixture was stirred at room temperature for one hr. Next, a solution of 1-(5-methyl-1,3-thiazol-2-yl)-1-ethylamine (35 mg) in chloroform (0.2 ml) was added thereto, and the mixture was stirred at room temperature for 10 hr. The stirred mixture was purified by chromatography on silica gel using chloroform/methanol for development to give the title compound (38 mg, yield 83%).
COc1cc(Oc2ccnc3cc(OC)c(OC)cc23)ccc1NC(=O)NC(C)c1ncc(C)s1
null
Cc1cnc(C(C)N)s1
O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
COc1cc(Oc2ccnc3cc(OC)c(OC)cc23)ccc1N
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[C:18]([O:23][CH3:24])[CH:17]=1.C(N(CC)CC)C.ClC(Cl)(O[C:36](=[O:42])OC(Cl)(Cl)Cl)Cl.[CH3:44][C:45]1[S:49][C:48]([CH:50]([NH2:52])[CH3:51])=[N:47][CH:46]=1>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:36]([NH:52][CH:50]([C:48]2[S:49][C:45]([CH3:44])=[CH:46][N:47]=2)[CH3:51])=[O:42])=[C:18]([O:23][CH3:24])[CH:17]=1
1
ClC(Cl)Cl
CCN(CC)CC
null
25
null
83.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
3,890
Cl
[Cl-]
null
null
ord_dataset-15ce1bcfb62046d9bec87d32620888d5
1976-01-01T00:03:00
true
A mixture of 33 g. (0.15 mole) of the compound of Example I, C. and 21 g. (0.15 mole) of p-dimethylaminoaniline in 1800 ml. of ethanol was refluxed overnight. The solvent was removed by evaporation in vacuo. The residue was recrystallized from ethanol to give 32 g. of yellow solid. The solid was dissolved methyl alcohol and was acidified with a saturated etherhydrogen chloride solution. The product was collected as a cream colored solid and was recrystallized from methyl alcohol to give a yellow solid melting at 210°-215° in a yield of 22 g. (42%). Recrystallization from methyl alcohol raised the melting point to 215°-217°.
Cc1cc(Nc2ccc(N(C)C)cc2)c2c(ccc3nc[nH]c32)n1
O
CCO
Cc1cc(Nc2ccccc2)c2c(ccc3nc[nH]c32)n1
CN(C)c1ccc(N)cc1
[ClH:1].[NH:2]([C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]3[N:21]=[CH:20][NH:19][C:17]3=2)[N:12]=[C:11]([CH3:22])[CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:23][N:24]([CH3:32])[C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=1.C([OH:35])C.[Cl-]>CO>[OH2:35].[ClH:1].[CH3:23][N:24]([CH3:25])[C:6]1[CH:7]=[CH:8][C:3]([NH:2][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]4[N:21]=[CH:20][NH:19][C:17]4=3)[N:12]=[C:11]([CH3:22])[CH:10]=2)=[CH:4][CH:5]=1.[OH2:35].[OH2:35].[CH3:23][N:24]([C:25]1[CH:31]=[CH:30][C:28]([NH:29][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]4[N:21]=[CH:20][NH:19][C:17]4=3)[N:12]=[C:11]([CH3:22])[CH:10]=2)=[CH:27][CH:26]=1)[CH3:32].[ClH:1]
null
CO
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
301,167
C[N+](C)(C)Cc1ccccc1
[Cl-]
[K+]
null
ord_dataset-9ad0840101374618a7d5c4e4521c82d1
1994-01-01T00:12:00
true
To a solution of dipotassium nitrodithioacetate (118 g) dissolved in water (630 ml), dimethylamine (1.1 equivalents) was added as a 40% w/w solution in water. After stirring for 6 hours at 20°-25° C., benzyltrimethylammonium chloride (7 g ) was charged followed by dimethyl sulphate (175 g ) over one hour. After stirring overnight, the reaction mixture was extracted three times with 100 ml aliquots of dichloromethane. After drying over MgSO4, the combined organic phases were concentrated to a red oil which was chromatographed on a silica gel column, using ethyl acetate as eluant to give, after recrystallisation from isopropanol, 36 g (40%) of the title compound, m.p. 60° C.
CSC(=C[N+](=O)[O-])N(C)C
null
O=[N+]([O-])CC(=S)[S-]
CNC
null
[N+:1]([CH2:4][C:5]([S-:7])=S)([O-:3])=[O:2].[K+].[K+].[N+]([CH2:13]C([S-])=S)([O-])=O.[CH3:17][NH:18][CH3:19].S(OC)(OC)(=O)=O>O.[Cl-].C([N+](C)(C)C)C1C=CC=CC=1>[CH3:17][N:18]([CH3:19])[C:5]([S:7][CH3:13])=[CH:4][N+:1]([O-:3])=[O:2]
6
COS(=O)(=O)OC
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
413,824
[Pd]
null
null
null
ord_dataset-275344fd078b4340b89ca0b6e92beb95
1998-01-01T00:10:00
true
0.33 g (0.83 mmol) of 1H-2-(3-nitrophenyl)benzimidazole-5-[N-(2-amidinoethyl)]carboxyamide hydrochloride was suspended in a mixed solvent of DMF and methanol, and catalytic hydrogenation was then carried out in the presence of 10% Pd/C as a catalyst to lead the above-mentioned compound to a corresponding amino compound. This DMF solution was stirred under ice cooling and under a nitrogen gas stream, and a methylene chloride solution of 4-[4-[N,N-bis(2-chloroethyl)amino]phenyl]butyryl chloride {which was prepared by adding 0.55 g (4.6 mmols, 5.0 eq.) of thionyl chloride to 0.28 g (0.92 mmol) of chlorambucil, removing thionyl chloride under reduced pressure after 5 minutes, and then carrying out azeotropic distillation with benzene twice} was added dropwise. The temperature of the suspension was returned to room temperature, followed by stirring for 7 hours. Next, the suspension was concentrated under reduced pressure, and the resulting residue was then purified through silica gel column chromatography (ethyl acetate/IPA/water=6/2/1), and then solidified with ethanol to obtain 0.23 g (0.36 mmols, 43.4%) of the desired compound in the state of light yellowish white crystals.
O=C(Cl)CCCc1ccc(N(CCCl)CCCl)cc1
null
O=S(Cl)Cl
O=C(O)CCCc1ccc(N(CCCl)CCCl)cc1
null
CN(C=O)C.CO.S(Cl)([Cl:10])=O.[CH:12]1[C:17]([CH2:18][CH2:19][CH2:20][C:21](O)=[O:22])=[CH:16][CH:15]=[C:14]([N:24]([CH2:28][CH2:29][Cl:30])[CH2:25][CH2:26][Cl:27])[CH:13]=1>[Pd].C(Cl)Cl>[Cl:27][CH2:26][CH2:25][N:24]([C:14]1[CH:15]=[CH:16][C:17]([CH2:18][CH2:19][CH2:20][C:21]([Cl:10])=[O:22])=[CH:12][CH:13]=1)[CH2:28][CH2:29][Cl:30]
7
CO
ClCCl
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
458,951
[Al+3]
[Cl-]
null
null
ord_dataset-2501595af7f242268dbaab34c9e7ae56
2000-01-01T00:02:00
true
To a solution of 12.0 g of anhydrous aluminum chloride in 150 ml of dry tetrahydrofuran were added successively a solution of 5.79 g of isatin-3,3-dimethylacetal in 150 ml of dry tetrahydrofuran and 9.0 g of p-tolylurea at 0° C. under a nitrogen atmosphere, and the mixture was heated under reflux for 40 minutes. Ethyl acetate was added to the reaction mixture, and the mixture was washed twice with an aqueous solution of sodium chloride. The organic layer was dried over anhydrous sodium sulfate, followed by concentration. To the residue was added 150 ml of ethyl ether, and insoluble matter was removed by filtration. The filtrate was concentrated and recrystallized from acetone to yield 4.61 g (36%) of the title compound as a white powder.
Cc1ccc(NC(=O)NC2(NC(=O)Nc3ccc(C)cc3)C(=O)Nc3ccccc32)cc1
null
CCOC(C)=O
Cc1ccc(NC(N)=O)cc1
null
[Cl-].[Al+3].[Cl-].[Cl-].[C:5]1([CH3:15])[CH:10]=[CH:9][C:8]([NH:11][C:12]([NH2:14])=[O:13])=[CH:7][CH:6]=1.C([O:19][CH2:20][CH3:21])(=O)C>O1CCCC1>[CH3:15][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:13])[NH:14][C:21]2([NH:14][C:12]([NH:11][C:8]3[CH:9]=[CH:10][C:5]([CH3:15])=[CH:6][CH:7]=3)=[O:13])[C:9]3[C:8](=[CH:7][CH:6]=[CH:5][CH:10]=3)[NH:11][C:20]2=[O:19])=[CH:7][CH:6]=1
null
C1CCOC1
null
null
null
null
36
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
241,474
null
null
null
null
ord_dataset-9f54014563f44962b72e288618421b97
1992-01-01T00:02:00
true
19.3 g (0.11 mol) of 5-formyl-2-acetylcyclohexane-1,3-dione in 200 ml of distilled water were initially taken, and 14.7 g (0.13 mol) of hydroxylamine-O-sulfonic acid were added at room temperature. The mixture was then stirred for 17 hours at room temperature. The precipitate was filtered off under suction, washed with water and dried. 11.5 g (61% of theory) of 3,5-dioxo-4-acetylcyclohexanenitrile of melting point 66-69° C. were obtained.
CC(=O)C1C(=O)CC(C#N)CC1=O
null
CC(=O)C1C(=O)CC(C=O)CC1=O
NOS(=O)(=O)O
null
[CH:1]([CH:3]1[CH2:8][C:7](=[O:9])[CH:6]([C:10](=[O:12])[CH3:11])[C:5](=[O:13])[CH2:4]1)=O.[NH2:14]OS(O)(=O)=O>O>[O:13]=[C:5]1[CH:6]([C:10](=[O:12])[CH3:11])[C:7](=[O:9])[CH2:8][CH:3]([C:1]#[N:14])[CH2:4]1
17
O
null
null
25
58.3
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,739,336
null
null
null
null
ord_dataset-eacfee6d16d8455a93348409f1b37be4
2016-01-01T00:06:00
true
The mixture of Et2Zn (1.1 M in toluene, 4 mL, 4.39 mmol) and CH2Cl2 (8 mL) was cooled to 0° C. TFA ((0.34 mL, 4.39 mmol) in CH2Cl2 (4 mL)) was added to the mixture at 0° C. The mixture was stirred at 0° C. for 1 hr. CH2I2 ((0.36 mL, 4.39 mmol) in CH2Cl2 (4 mL)) was added to the mixture at 0° C. The mixture was stirred at 0° C. for 1 hr. The acetate 179 ((270 mg, 0.44 mmol) in CH2Cl2 (4 mL)) was added to the mixture at 0° C. The mixture was warmed up to rt slowly and stirred at room temperature for 15 hours. The mixture was extracted with EtOAc/aq. sat'd NH4Cl (50 mL/50 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified using normal phase column chromatography to provide the title product 180 (152 mg, 55%).
CC(=O)OC[C@H]1O[C@@H](c2cc(Cc3ccc(C4CC4)cc3)c(Cl)c3c2CCCO3)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
null
CC[Zn]CC
C=Cc1ccc(Cc2cc([C@@H]3O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]3OC(C)=O)c3c(c2Cl)OCCC3)cc1
null
[Zn](CC)[CH2:2]C.C(O)(C(F)(F)F)=O.C(I)I.[C:16]([O:19][C@H:20]1[C@H:25]([O:26][C:27](=[O:29])[CH3:28])[C@@H:24]([O:30][C:31](=[O:33])[CH3:32])[C@H:23]([C:34]2[CH:43]=[C:42]([CH2:44][C:45]3[CH:50]=[CH:49][C:48]([CH:51]=[CH2:52])=[CH:47][CH:46]=3)[C:41]([Cl:53])=[C:40]3[C:35]=2[CH2:36][CH2:37][CH2:38][O:39]3)[O:22][C@@H:21]1[CH2:54][O:55][C:56](=[O:58])[CH3:57])(=[O:18])[CH3:17]>C(Cl)Cl>[C:16]([O:19][C@H:20]1[C@H:25]([O:26][C:27](=[O:29])[CH3:28])[C@@H:24]([O:30][C:31](=[O:33])[CH3:32])[C@H:23]([C:34]2[CH:43]=[C:42]([CH2:44][C:45]3[CH:50]=[CH:49][C:48]([CH:51]4[CH2:2][CH2:52]4)=[CH:47][CH:46]=3)[C:41]([Cl:53])=[C:40]3[C:35]=2[CH2:36][CH2:37][CH2:38][O:39]3)[O:22][C@@H:21]1[CH2:54][O:55][C:56](=[O:58])[CH3:57])(=[O:18])[CH3:17]
1
ICI
O=C(O)C(F)(F)F
ClCCl
0
null
54.9
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
668,911
null
null
null
null
ord_dataset-e90cd41afe844e49875435eb99903799
2005-01-01T00:05:00
true
Benzyl 2-[(4-cyanophenoxy)methyl]-1-aziridinecarboxylate (1.0 g; 3.2 mmol; from step (iii) above) was mixed with tert-butyl 3,7-diazabicyclo[3.3.1]nonane-3-carboxylate (from step (v) above; 0.73 g; 3.2 mmol) and 30 mL of iso-propanol, and stirred at 60° C. for 5 h, and then at rt overnight. The solvent was evaporated and the crude material was purified on silica (DCM:5% MeOH) yielding 1.3 g (76%) of sub-title compound.
CC(C)(C)OC(=O)N1CC2CC(CN(CC(COc3ccc(C#N)cc3)NC(=O)OCc3ccccc3)C2)C1
null
CC(C)(C)OC(=O)N1CC2CNCC(C2)C1
N#Cc1ccc(OCC2CN2C(=O)OCc2ccccc2)cc1
null
[C:1]([C:3]1[CH:23]=[CH:22][C:6]([O:7][CH2:8][CH:9]2[CH2:11][N:10]2[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])=[CH:5][CH:4]=1)#[N:2].[CH:24]12[CH2:32][CH:28]([CH2:29][NH:30][CH2:31]1)[CH2:27][N:26]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:25]2>C(O)(C)C>[CH2:15]([O:14][C:12]([NH:10][CH:9]([CH2:8][O:7][C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:23][CH:22]=1)[CH2:11][N:30]1[CH2:31][CH:24]2[CH2:32][CH:28]([CH2:27][N:26]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:25]2)[CH2:29]1)=[O:13])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
5
CC(C)O
null
null
60
76
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
444,608
Oc1ccc(OCc2ccccc2)cc1
null
null
null
ord_dataset-ba7561dae3884c07a8beddd0b9f1222e
1999-01-01T00:10:00
true
To a solution of 3-bromo-benzo[b]thiophene (69.62 g, 0.325 mol) in 55 mL of anhydrous collidine under N2 was added 4-benzyloxyphenol (97.6 g, 0.488 mol) and cuprous oxide (23.3 g, 0.163 mol). The mixture was heated to reflux for 24 hours. Upon cooling, the reaction mixture was diluted with ethyl acetate (200 mL) and the crude mixture filtered through a pad of Celite® (Aldrich, Milwaukee, Wis.) to remove inorganic salts. The filtrate was washed with 1N hydrochloric acid (3×150 mL). The organic was dried (sodium sulfate) and concentrated in vacuo to a liquid. Thianaphthene was removed by distillation (10 mm Hg, 115-120° C.). The remainder of the material was chromatographed (silicon dioxide, hexanes:ethyl acetate 85:15) to provide 12.2 g of benzo[b]thiophene and 12.95 g (35% based on recovered starting material) of [3-(4-benzyloxy)phenoxy]benzo-[b]thiophene as an off-white solid. mp 84-86° C. 1H NMR (CDCl3) d 7.91-7.83 (m, 2H), 7.47-7.34 (m, 7H), 7.04 (q, JAB =9.0 Hz, 4H), 6.47 (s, 1H), 5.07 (s, 2H). Anal. Calcd. for C21H16O2S: C, 75.88; H, 4.85. Found: C, 75.75; H, 5.00.
c1ccc2sccc2c1
null
Brc1csc2ccccc12
null
null
Br[C:2]1[C:3]2[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=2[S:5][CH:6]=1.C(OC1C=CC(O)=CC=1)C1C=CC=CC=1>N1C(C)=CC(C)=CC=1C.C(OCC)(=O)C>[S:5]1[CH:6]=[CH:2][C:3]2[CH:10]=[CH:9][CH:8]=[CH:7][C:4]1=2
null
CCOC(C)=O
Cc1cc(C)nc(C)c1
null
null
28
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,495,901
null
null
null
null
ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2
2014-01-01T00:10:00
true
The title compound was synthesized from N-cyclobutyl-6-ethynylpyridazin-3-amine and 3-iodo-4-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)benzamide (as prepared above) in a manner similar to that described for in Example 1. The product was obtained as a pale yellow solid. Mp: 223-225° C.; 1H NMR (300 MHz, DMSO-d6) δ: 10.72 (1H, s), 8.31 (1H, s), 8.17-8.22 (2H, m), 7.94-7.96 (1H, dd, J=1.5 and 8.1 Hz), 7.75 (1H, s), 7.47-7.61 (4H, m), 6.77-6.80 (1H, d, J=9.0 Hz), 4.42 (1H, m), 2.56 (3H, s), 2.33-2.35 (2H, m), 2.19 (3H, brs), 1.88-1.99 (2H, m), 1.72-1.78 (2H, m). HRMS (ESI-TOF+): m/z [M+H]+ calcd for C29H26F3N6O: 531.2115. found: 531.2113.
Cc1cn(-c2cc(NC(=O)c3ccc(C)c(C#Cc4ccc(NC5CCC5)nn4)c3)cc(C(F)(F)F)c2)cn1
null
C#Cc1ccc(NC2CCC2)nn1
Cc1cn(-c2cc(NC(=O)c3ccc(C)c(I)c3)cc(C(F)(F)F)c2)cn1
null
[CH:1]1([NH:5][C:6]2[N:7]=[N:8][C:9]([C:12]#[CH:13])=[CH:10][CH:11]=2)[CH2:4][CH2:3][CH2:2]1.I[C:15]1[CH:16]=[C:17]([CH:37]=[CH:38][C:39]=1[CH3:40])[C:18]([NH:20][C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([N:31]2[CH:35]=[C:34]([CH3:36])[N:33]=[CH:32]2)[CH:22]=1)=[O:19]>>[CH:1]1([NH:5][C:6]2[N:7]=[N:8][C:9]([C:12]#[C:13][C:15]3[CH:16]=[C:17]([CH:37]=[CH:38][C:39]=3[CH3:40])[C:18]([NH:20][C:21]3[CH:26]=[C:25]([C:27]([F:29])([F:28])[F:30])[CH:24]=[C:23]([N:31]4[CH:35]=[C:34]([CH3:36])[N:33]=[CH:32]4)[CH:22]=3)=[O:19])=[CH:10][CH:11]=2)[CH2:4][CH2:3][CH2:2]1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,596,258
Cl
null
null
null
ord_dataset-e8c6a25568b64529b960953990e6921f
2015-01-01T00:06:00
true
First, 12.6 g (43.3 mmol) of N-[1-chloro-1-(2-methylphenyl)methylidene]-N′-[1-chloro(1-phenyl)methylidene]hydrazine, 15.7 g (134.5 mmol) of 2,6-dimethylaniline, and 100 mL of N,N-dimethylaniline were put into a 500 mL recovery flask and heated and stirred at 120° C. for 20 hours. After reaction for a predetermined time, this reaction solution was slowly added to 200 mL of 1N hydrochloric acid. Dichloromethane was added to this solution and a target substance was extracted to an organic layer. The obtained organic layer was washed with water and an aqueous solution of sodium hydrogen carbonate, and was dried with magnesium sulfate. The magnesium sulfate was removed by gravity filtration, and the obtained filtrate was concentrated to give a black liquid. This liquid was purified by silica gel column chromatography. A mixed solvent of ethyl acetate and hexane in a ratio of 1:5 was used as a developing solvent. The obtained fraction was concentrated to give a white solid. This solid was recrystallized from ethyl acetate to give 4.5 g of a white solid of Hmpptz-dmp in a yield of 31%. A synthetic scheme of Step 1 is shown below.
Cc1ccccc1-c1nnc(-c2ccccc2)n1-c1c(C)cccc1C
null
Cc1ccccc1C(Cl)=NN=C(Cl)c1ccccc1
Cc1cccc(C)c1N
null
Cl[C:2](=[N:10][N:11]=[C:12](Cl)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH3:9].[CH3:20][C:21]1[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[C:22]=1[NH2:23].CN(C)C1C=CC=CC=1.Cl>ClCCl>[CH3:9][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[C:2]1[N:23]([C:22]2[C:24]([CH3:28])=[CH:25][CH:26]=[CH:27][C:21]=2[CH3:20])[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:11][N:10]=1
20
CN(C)c1ccccc1
ClCCl
null
120
null
30.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,262,770
null
null
null
null
ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0
2013-01-01T00:02:00
true
4-(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-piperazine-1-carboxylic acid (2-methoxy-ethyl)-methyl-amide (Example 27) was reacted with 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine in General Procedure A. Purification on silica yielded 156. NMR (CDCl3): 2.57-2.59 (m, 4H, 2×CH2), 2.92 (s, 3H, CH3), 3.30-3.32 (m, 4H, 2×CH2), 3.36 (s, 3H, CH3), 3.38-3.41 (m, 4H, 2×CH2), 3.55-3.58 (m, 4H, 2×CH2), 3.85 (s, 2H, CH2), 3.89-3.91 (m, 4H, 2×CH2), 4.04-4.06 (m, 4H, 2×CH2), 4.67 (sbr, 2H, NH2), 6.58 (d, H, ArH, J=8.64 Hz), 7.29 (s, H, ArH), 8.48 (dd, H, ArH, J=2.2 Hz, 8.6 Hz), 9.17 (d, H, ArH, J=2.02 Hz). MS: (ESI+): MH+ 527.49
COCCN(C)C(=O)N1CCN(Cc2cc3nc(-c4ccc(N)nc4)nc(N4CCOCC4)c3s2)CC1
null
CC1(C)OB(c2ccc(N)nc2)OC1(C)C
COCCN(C)C(=O)N1CCN(Cc2cc3nc(Cl)nc(N4CCOCC4)c3s2)CC1
null
[CH3:1][O:2][CH2:3][CH2:4][N:5]([CH3:31])[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[S:23][C:22]3[C:21]([N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[N:20][C:19](Cl)=[N:18][C:17]=3[CH:16]=2)[CH2:10][CH2:9]1)=[O:7].CC1(C)C(C)(C)OB([C:40]2[CH:41]=[CH:42][C:43]([NH2:46])=[N:44][CH:45]=2)O1>>[NH2:46][C:43]1[N:44]=[CH:45][C:40]([C:19]2[N:20]=[C:21]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[C:22]3[S:23][C:15]([CH2:14][N:11]4[CH2:12][CH2:13][N:8]([C:6]([N:5]([CH2:4][CH2:3][O:2][CH3:1])[CH3:31])=[O:7])[CH2:9][CH2:10]4)=[CH:16][C:17]=3[N:18]=2)=[CH:41][CH:42]=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
52,749
null
null
null
null
ord_dataset-3d470a6df4a04b1996e024a38c53e818
1979-01-01T00:03:00
true
An amount of 137.4 g of palmitoyl chloride in 100 ml of ethyl ether was added, under stirring at room temperature, to 80.5 g of n-butylamine in 700 ml of ethyl ether. Stirring was continued under gentle reflux for one hour. The precipitate was filtered off and thoroughly washed with water. The reaction product was recrystallized from ethanol giving 148.4 g of the title compound, melting point 74°-76° C.
CCCCCCCCCCCCCCCC(=O)NCCCC
null
CCCCN
CCCCCCCCCCCCCCCC(=O)Cl
null
[C:1](Cl)(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[CH2:19]([NH2:23])[CH2:20][CH2:21][CH3:22]>C(OCC)C>[CH2:19]([NH:23][C:1](=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:20][CH2:21][CH3:22]
null
CCOCC
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
864,478
[C-]#N
[Na+]
null
null
ord_dataset-b8b98725045d45bdbd73512048f4b47e
2009-01-01T00:02:00
true
Using general procedure A with 1,4-benzodioxan-6-amine (170 mg, 1.1 mmol) and (R)-3-(4-oxo-piperidin-1-yl)-butyronitrile (206 mg, 1.2 mmol) followed by general procedure J gave a green oil, which was subsequently treated with a solution of NaCN (175 mg) in H2O (5 mL) and MeOH (5 mL) and stirred at room temperature for 20 minutes. Work-up and purification afforded [1-((R)-3-amino-1-methyl-propyl)-piperidin-4-yl]-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-amine as a white solid (245 mg, 71% over 2 steps).
C[C@H](CCN)N1CCC(Nc2ccc3c(c2)OCCO3)CC1
null
Nc1ccc2c(c1)OCCO2
C[C@H](CC#N)N1CCC(=O)CC1
null
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([NH2:11])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.O=[C:13]1[CH2:18][CH2:17][N:16]([C@H:19]([CH3:23])[CH2:20][C:21]#[N:22])[CH2:15][CH2:14]1.[C-]#N.[Na+]>O.CO>[NH2:22][CH2:21][CH2:20][C@H:19]([N:16]1[CH2:17][CH2:18][CH:13]([NH:11][C:9]2[CH:8]=[CH:7][C:6]3[O:1][CH2:2][CH2:3][O:4][C:5]=3[CH:10]=2)[CH2:14][CH2:15]1)[CH3:23]
0.33
O
CO
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
689,149
Cl
O=C([O-])[O-]
[K+]
null
ord_dataset-6214af00a7eb47f3887ef21a94320a7e
2005-01-01T00:11:00
true
3-Bromophenol (1.00 g, 5.8 mmol), 2-picolyl chloride hydrochloride (950 mg, 5.8 mmol) and potassium carbonate (3.20 g, 23 mmol) were stirred together in DMF (10 mL) at room temperature overnight. The solvent was removed in vacuo, azeotroping with xylene to remove the last traces of DMF. The residual material was partitioned between ethyl acetate (70 mL) and water (70 mL), then the organic phase was washed with saturated sodium chloride solution (1×50 mL), was dried over magnesium sulfate, and was concentrated in vacuo to afford 2-(3-bromophenoxymethyl)pyridine (1.48 g, 97%). m/z (ES+) 265 [MH]+.
Brc1cccc(OCc2ccccn2)c1
null
ClCc1ccccn1
Oc1cccc(Br)c1
null
[Br:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.Cl.[N:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16]Cl.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[O:8][CH2:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][N:10]=1
null
CN(C)C=O
null
null
null
null
96.6
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,379,223
null
null
null
null
ord_dataset-d23f2f15886d4c22b7d7ba5f0e203e81
2013-01-01T00:12:00
true
(S)-3-{3-[5-(2-Trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-pyridin-2-ylamino}-pyrrolidine-1-carboxylic acid methyl ester was prepared from (S)-pyrrolidin-3-yl-{3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-pyridin-2-yl}-amine and methylchloroformate, using DIPEA as base and following the general synthetic procedures described in the above Examples.
COC(=O)N1CC[C@H](Nc2ncccc2-c2cnc3c(ccn3COCC[Si](C)(C)C)n2)C1
null
C[Si](C)(C)CCOCn1ccc2nc(-c3cccnc3N[C@H]3CCNC3)cnc21
COC(=O)Cl
null
[NH:1]1[CH2:5][CH2:4][C@H:3]([NH:6][C:7]2[C:12]([C:13]3[N:14]=[C:15]4[CH:21]=[CH:20][N:19]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:16]4=[N:17][CH:18]=3)=[CH:11][CH:10]=[CH:9][N:8]=2)[CH2:2]1.[CH3:30][O:31][C:32](Cl)=[O:33].CCN(C(C)C)C(C)C>>[CH3:30][O:31][C:32]([N:1]1[CH2:5][CH2:4][C@H:3]([NH:6][C:7]2[C:12]([C:13]3[N:14]=[C:15]4[CH:21]=[CH:20][N:19]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:16]4=[N:17][CH:18]=3)=[CH:11][CH:10]=[CH:9][N:8]=2)[CH2:2]1)=[O:33]
null
CCN(C(C)C)C(C)C
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,664,634
[Na+]
[OH-]
null
null
ord_dataset-9cc455db05a444779921f786a45b21a6
2015-01-01T00:12:00
true
The title compound was prepared in analogy to example 12 step B from a mixture of 6-chloro-4-(2-chloro-benzyl)-2-diethylamino-quinoline-3-carboxylic acid ethyl ester (50 mg, 0.116 mmol) and 1N NaOH. Pale yellow solid (32 mg, 68%). LC-MS (ESI): 403 (M+H)+.
CCN(CC)c1nc2ccc(Cl)cc2c(Cc2ccccc2Cl)c1C(=O)O
null
CCOC(=O)c1c(N(CC)CC)nc2ccc(Cl)cc2c1Cc1ccccc1Cl
null
null
C([O:3][C:4]([C:6]1[C:7]([N:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[N:8][C:9]2[C:14]([C:15]=1[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[Cl:23])=[CH:13][C:12]([Cl:24])=[CH:11][CH:10]=2)=[O:5])C.[OH-].[Na+]>>[Cl:24][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([N:25]([CH2:28][CH3:29])[CH2:26][CH3:27])[C:6]([C:4]([OH:5])=[O:3])=[C:15]2[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[Cl:23]
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,597,527
[Cu+2]
O=S(=O)([O-])[O-]
null
null
ord_dataset-e8c6a25568b64529b960953990e6921f
2015-01-01T00:06:00
true
The solution of (Z)-2-(2-tert-butoxyvinyl)-5-methylpyridine (12-3) (1.20 g, 6.27 mmol) in toluene (20 mL) and anhydrous copper sulfate (100 mg, 0.63 mmol) was heated to 75° C. Then the solution of ethyl diazoacetate (2.17 g, 18.8 mmol) in toluene (10 mL) was added dropwise over 2 h. It was heated for another 2 h after the addition was completed. The mixture was restored to room temperature for overnight. The solvent was removed under reduced pressure and the residue was purified by silca gel chromatography with gradient eluent (PE/EA=40/1; 20/1; 10/1). The product was obtained as a yellow oil (500 mg, 34%). LRMS (ES) calculated M+H for C16H24NO3: 278.3. Found: 278.2.
CCOC(=O)C1C(OC(C)(C)C)C1c1ccc(C)cn1
null
Cc1ccc(/C=C\OC(C)(C)C)nc1
CCOC(=O)C=[N+]=[N-]
null
[C:1]([O:5]/[CH:6]=[CH:7]\[C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].[N+](=[CH:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[N-]>C1(C)C=CC=CC=1.S([O-])([O-])(=O)=O.[Cu+2]>[C:1]([O:5][CH:6]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][N:9]=2)[CH:17]1[C:18]([O:20][CH2:21][CH3:22])=[O:19])([CH3:4])([CH3:3])[CH3:2]
8
Cc1ccccc1
null
null
null
28.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,043,164
null
null
null
null
ord_dataset-3af92aec23dc4810b92eb0d8c60023ee
2011-01-01T00:03:00
true
Isopropyl-thiourea (2.47 mmol) and 3-(2-Bromo-acetyl)-benzoic acid (2.47 mmol) were mixed in THF (12 mL). After stirring at room temperature for 5 minutes the mixture was heated to 80° C. for 2 hours. The volume was reduced to 5 mL and the mixture was then cooled to −20° C. and filtered. The solid was washed with a small amount of diethylether and dried. m/z=263.1 in MS ES+, which was characterized by hplc and MS and used in the next step without any further purification.
CC(C)Nc1nc(-c2cccc(C(=O)O)c2)cs1
null
O=C(O)c1cccc(C(=O)CBr)c1
CC(C)NC(N)=S
null
[CH:1]([NH:4][C:5]([NH2:7])=[S:6])([CH3:3])[CH3:2].Br[CH2:9][C:10]([C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[C:15]([OH:17])=[O:16])=O>C1COCC1>[CH:1]([NH:4][C:5]1[S:6][CH:9]=[C:10]([C:12]2[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=2)[C:15]([OH:17])=[O:16])[N:7]=1)([CH3:3])[CH3:2]
0.08
C1CCOC1
null
null
25
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
14,286
null
null
null
null
ord_dataset-7f88a5da29d74264aae5239be74b3981
1976-01-01T00:10:00
true
1,2,4,5-Tetrahydro-11-propyl-3-azepino[4,5-b]quinoline-carboxylic acid ethyl ester hydrochloride was prepared from 1,2,4,5-tetrahydro-11-propyl-3H-azepino[4,5-b]quinoline and ethyl chloroformate analogous to Example 63.
CCCc1c2c(nc3ccccc13)CCN(C(=O)OCC)CC2
Cl
CCCc1c2c(nc3ccccc13)CCNCC2
CCOC(=O)Cl
null
[CH2:1]([C:4]1[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:7]=[C:6]2[CH2:14][CH2:15][NH:16][CH2:17][CH2:18][C:5]=12)[CH2:2][CH3:3].[Cl:19][C:20]([O:22][CH2:23][CH3:24])=[O:21]>>[ClH:19].[CH2:23]([O:22][C:20]([N:16]1[CH2:17][CH2:18][C:5]2[C:6](=[N:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[C:4]=2[CH2:1][CH2:2][CH3:3])[CH2:14][CH2:15]1)=[O:21])[CH3:24]
null
null
null
null
null
null
84
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
50,377
O=C([O-])[O-]
[I-]
[K+]
null
ord_dataset-e5870fef54544989915ccced8dd8d849
1979-01-01T00:01:00
true
A mixture of 26.3 g. (0.0758 mole) of 4-(6-bromohexyl)-3,5-heptanedione, 13.1 g. (0.0787 mole) of ethyl p-hydroxybenzoate, 31.5 g. (0.228 mole) of powdered potassium carbonate, 4 g. of potassium iodide and 500 ml. of acetone was heated at reflux for 36 hours. The reaction mixture was concentrated in vacuo and partitioned between water and methylene dichloride. The organic layer was washed successively with sodium hydroxide solution, water, hydrochloric acid, water and sodium chloride solution, and then dried over anhydrous magnesium sulfate. The solution was concentrated and the residue crystallized and recrystallized from n-pentane to give 4-[10-(4-carbethoxyphenoxy)decyl]-3,5-heptanedione, m.p. 45°-46° C.
CCOC(=O)c1ccc(OCCCCCCCCCCC(C(=O)CC)C(=O)CC)cc1
null
CCC(=O)C(CCCCCCBr)C(=O)CC
CCOC(=O)c1ccc(O)cc1
null
Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH:8]([C:13](=[O:16])[CH2:14][CH3:15])[C:9](=[O:12])[CH2:10][CH3:11].[OH:17][C:18]1[CH:28]=[CH:27][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(C)=O>[C:22]([C:21]1[CH:20]=[CH:19][C:18]([O:17][CH2:2][CH2:3][CH2:4][CH2:5][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH:8]([C:13](=[O:16])[CH2:14][CH3:15])[C:9](=[O:12])[CH2:10][CH3:11])=[CH:28][CH:27]=1)([O:24][CH2:25][CH3:26])=[O:23]
null
CC(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
587,238
null
null
null
null
ord_dataset-cb5dd7a8b94e4f19a9148a1904b0dcb6
2003-01-01T00:03:00
true
Kalnin, Helv. Chim. Acta 11, 977 (1928) describes various salts as catalysts. 1 mol of benzaldehyde and 1.5 mol of acetic anhydride are refluxed at 180° C. for 8 hours with 0.65 mol of catalyst. The yields of cinnamic acid are, following work-up, for potassium acetate 72%, for potassium carbonate 59%, for sodium carbonate 40%, for sodium acetate 39%, for sodium phosphate 36%, for potassium phosphate 20% and for potassium sulphide 32%. As well as potassium and sodium salts, amines are also possible as catalysts. For 0.33 mol of triethylamine, the yield is 19%.
O=C(O)C=Cc1ccccc1
null
CC(=O)OC(C)=O
O=Cc1ccccc1
null
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([O:12]C(=O)C)(=[O:11])[CH3:10]>>[C:9]([OH:12])(=[O:11])[CH:10]=[CH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
null
null
null
null
null
null
19
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
716,798
null
null
null
null
ord_dataset-c8a367b56b4f406b878f51867b157d19
2006-01-01T00:06:00
true
To a stirred solution of 6-(3-hydroxy-propoxy)-1-(3-ethoxy-benzoyl)-7-methoxy-isoquinoline-4-carbaldehyde (40 mg, 0.10 mmol) in pyridine (8 mL) was added acetic anhydride (0.4 mL). The reaction mixture was stirred at room temperature for 15 hrs. The mixture was concentrated in vacuo to afford 6-(3-acetoxy-propoxy)-1-(3-ethoxy-benzoyl)-7-methoxy-isoquinoline-4-carbaldehyde (60 mg, 99% yield). The crude product was used without further purification.
CCOc1cccc(C(=O)c2ncc(C=O)c3cc(OCCCOC(C)=O)c(OC)cc23)c1
null
CC(=O)OC(C)=O
CCOc1cccc(C(=O)c2ncc(C=O)c3cc(OCCCO)c(OC)cc23)c1
null
[OH:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[O:16][CH3:17])[C:12]([C:18](=[O:28])[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH2:26][CH3:27])[CH:20]=1)=[N:11][CH:10]=[C:9]2[CH:29]=[O:30].[C:31](OC(=O)C)(=[O:33])[CH3:32]>N1C=CC=CC=1>[C:31]([O:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[O:16][CH3:17])[C:12]([C:18](=[O:28])[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH2:26][CH3:27])[CH:20]=1)=[N:11][CH:10]=[C:9]2[CH:29]=[O:30])(=[O:33])[CH3:32]
15
c1ccncc1
null
null
25
null
99
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
184,496
[Na]
null
null
null
ord_dataset-8537fa92abf34c849134600c0c2bbcc7
1989-01-01T00:02:00
true
0.28 g (0.012 g.-atoms) of sodium are dissolved in 2.70 g (36 mmoles) of N-methylamino-ethanol, 2.36 g (5.86 mmoles) of 2-phenyl-3,3,3-trifluoro-1-(4-fluorophenyl)-1-(4-methoxymethoxy-phenyl)-propene, prepared as described in Example 33, are added, and the mixture is heated at 150° C. for one hour. The mixture is cooled, diluted with 100 ml of ether, washed with water until neutral, dried and evaporated. The residue is crystallized from hexane. 1.94 g (72.4%) of 2-phenyl-3,3,3-trifluoro-1-[4-(2-methylaminoethoxy)-phenyl]-1-(4-methoxymethoxy-phenyl)-propene are obtained; m.p.: 87°-90° C.
CNCCOc1ccc(C(=C(c2ccccc2)C(F)(F)F)c2ccc(OCOC)cc2)cc1
null
COCOc1ccc(C(=C(c2ccccc2)C(F)(F)F)c2ccc(F)cc2)cc1
CCOCC
CNC(C)O
[Na].[CH3:2][NH:3][CH:4](O)[CH3:5].[C:7]1([C:13]([C:32]([F:35])([F:34])[F:33])=[C:14]([C:25]2[CH:30]=[CH:29][C:28](F)=[CH:27][CH:26]=2)[C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][O:23][CH3:24])=[CH:17][CH:16]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.CC[O:38]CC>>[C:7]1([C:13]([C:32]([F:33])([F:34])[F:35])=[C:14]([C:25]2[CH:26]=[CH:27][C:28]([O:38][CH2:5][CH2:4][NH:3][CH3:2])=[CH:29][CH:30]=2)[C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][O:23][CH3:24])=[CH:17][CH:16]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
null
null
null
null
150
72.4
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
215,931
null
null
null
null
ord_dataset-5ebf3d05077a4f7fb91a1cd9bdc504d2
1990-01-01T00:09:00
true
The title compound was obtained by coupling 4-(2-chlorophenyl)-2-iodo-9-methyl-6H-thieno [3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine with 2-ethynylpyridine under the conditions used in Example 37. The product was isolated by chromatography over the 50-fold amount of silica gel using 5% (v/v) of ethanol in methylene chloride. The fractions homogenous by TLC were combined and evaporated. Crystallization of the residue from ethyl acetate and recrystallization from tetrahydrofuran/methanol gave off-white crystals of 4-(2-chlorophenyl)-9-methyl-2-[2-(2-pyridinyl)-ethynyl]-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine with m.p. 153°-155°.
Cc1nnc2n1-c1sc(C#Cc3ccccn3)cc1C(c1ccccc1Cl)=NC2
null
Cc1nnc2n1-c1sc(I)cc1C(c1ccccc1Cl)=NC2
C#Cc1ccccn1
null
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16](I)[S:17][C:13]=2[N:12]2[C:19]([CH3:22])=[N:20][N:21]=[C:11]2[CH2:10][N:9]=1.[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1)#[CH:24].C(O)C>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([C:24]#[C:23][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=3)[S:17][C:13]=2[N:12]2[C:19]([CH3:22])=[N:20][N:21]=[C:11]2[CH2:10][N:9]=1
null
ClCCl
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
12,621
[Li]c1ccccc1
null
null
null
ord_dataset-a0071d97083e4e69ae8872417ed2776b
1976-01-01T00:09:00
true
To 3.6 g. of 6-aminoveratronitrile, dissolved in 75 ml. of anhydrous benzene, a solution of phenyl lithium (prepared from 0.35 g. of lithium and 3.9 g. of bromobenzene) in 60 ml. of anhydrous diethyl ether is added under a nitrogen atmosphere. After 45 minutes 4.4 g. of 1-cyano-4-(2-furoyl)piperazine in 50 ml. of anhydrous benzene are added. The ether and part of the benzene are distilled off and 100 ml. of tetrahydrofuran are added. The mixture is refluxed under the nitrogen atmosphere for 20 hours and then decomposed with water. The liquid is distilled off and 75 ml. of water are added to the residue. The mixture is extracted with chloroform and the extract is concentrated by evaporation of the solvent. 1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)4-(2-furoyl)piperazine is obtained. The product after crystallization from a mixture of ethanol and water melts at 258°-260°C.
COc1cc2nc(N3CCN(C(=O)c4ccco4)CC3)nc(N)c2cc1OC
null
COc1cc(N)c(C#N)cc1OC
N#CN1CCN(C(=O)c2ccco2)CC1
null
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([O:12][CH3:13])[CH:3]=1.C1([Li])C=CC=CC=1.[C:21]([N:23]1[CH2:28][CH2:27][N:26]([C:29]([C:31]2[O:32][CH:33]=[CH:34][CH:35]=2)=[O:30])[CH2:25][CH2:24]1)#[N:22]>C1C=CC=CC=1.C(OCC)C>[NH2:9][C:8]1[C:7]2[C:2](=[CH:3][C:4]([O:12][CH3:13])=[C:5]([O:10][CH3:11])[CH:6]=2)[N:1]=[C:21]([N:23]2[CH2:24][CH2:25][N:26]([C:29]([C:31]3[O:32][CH:33]=[CH:34][CH:35]=3)=[O:30])[CH2:27][CH2:28]2)[N:22]=1
0.75
c1ccccc1
CCOCC
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
862,309
O=C([O-])[O-]
[Na+]
null
null
ord_dataset-b8b98725045d45bdbd73512048f4b47e
2009-01-01T00:02:00
true
A solution of benzoic acid N′-[3-(2-bromo-phenyl)-propionyl]-N′-isopropyl-hydrazide (50 mg, 0.13 mmol) in DME (4 ml)/2M Na2CO3 (225 μL, 0.45 mmol) was treated with 3-methyl-phenylboronic acid (26 mg, 0.19 mmol) and Pd[PPh3]4 (15 mg, 0.013 mmol) for 18 hours at 90° C. The reaction mixture was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude was absorbed on silica and purified on a silica gel column with a 20-50% ethyl acetate/hexanes gradient to afford the product as a solid (48 mg, 93%). LC-MS m/e 401.37 (M+H+)
Cc1cccc(-c2ccccc2CCC(=O)N(NC(=O)c2ccccc2)C(C)C)c1
null
Cc1cccc(B(O)O)c1
CC(C)N(NC(=O)c1ccccc1)C(=O)CCc1ccccc1Br
null
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][C:10]([N:12]([CH:22]([CH3:24])[CH3:23])[NH:13][C:14](=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:11].C([O-])([O-])=O.[Na+].[Na+].[CH3:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1>COCCOC>[CH:22]([N:12]([C:10](=[O:11])[CH2:9][CH2:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:36]1[CH:35]=[CH:34][CH:33]=[C:32]([CH3:31])[CH:37]=1)[NH:13][C:14](=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:24])[CH3:23]
null
COCCOC
null
null
null
null
92.2
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
24,750
O=C([O-])[O-]
[K+]
null
null
ord_dataset-fcf7c02bbb814fe696760b5fbfee16bb
1977-01-01T00:05:00
true
(0.005 mol.) of 2-(4-hydroxybenzoyl)-3-phenylbenzofuran with 2.7 g. (0.02 mol.) of 2-diethylaminoethyl chloride in 50 ml. of acetone containing 2.7 g. (0.02 mol.) of potassium carbonate for three hours according to the procedure described in Example 1 gives the title compound.
CCN(CC)CCOc1ccc(C(=O)c2oc3ccccc3c2-c2ccccc2)cc1
null
O=C(c1ccc(O)cc1)c1oc2ccccc2c1-c1ccccc1
CCN(CC)CCCl
null
[OH:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([C:8]2[O:9][C:10]3[CH:22]=[CH:21][CH:20]=[CH:19][C:11]=3[C:12]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:7])=[CH:4][CH:3]=1.[CH2:25]([N:27]([CH2:31][CH3:32])[CH2:28][CH2:29]Cl)[CH3:26].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:25]([N:27]([CH2:31][CH3:32])[CH2:28][CH2:29][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([C:8]2[O:9][C:10]3[CH:22]=[CH:21][CH:20]=[CH:19][C:11]=3[C:12]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:7])=[CH:23][CH:24]=1)[CH3:26]
null
CC(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
1,400,593
F[P-](F)(F)(F)(F)F
null
null
null
ord_dataset-12dc3bd21bcf44d09e5b4249afe15161
2014-01-01T00:02:00
true
In a 16×100 mm screw cap test tube were added HATU (28.0 mg, 73.5 μmol.20) and propan-2-amine (14.5 mg, 21.0 μL, 245 μmol) then 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (30 mg, 61.3 μmol) and DMF (2 mL). The reaction mixture was stirred at 25° C. for 15 h. Propan-2-amine (14.5 mg, 21.0 μL, 245 μmol) and HATU (28.0 mg, 73.5 μmol) were added. After 3 h the solvents were evaporated and the residue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco, 0 to 50% EtOAc in hexanes over 30 min) to yield 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (32.5 mg, 61.3 μmol, 100%) as a light yellow solid. MS (M+Na)+=553.1; 1H NMR (CDCl3) δ: 9.25 (s, 1H), 8.40 (s, 1H), 8.27 (d, J=2.3 Hz, 1H), 8.20 (d, J=7.6 Hz, 1H), 7.45-7.53 (m, 1H), 7.36 (dd, J=8.9, 2.1 Hz, 1H), 6.53 (t, J=74.0 Hz, 1H), 5.73 (s, 2H), 4.38-4.59 (m, 1H), 4.21 (s, 3H), 3.55-3.64 (m, 2H), 1.42 (d, J=6.4 Hz, 6H), 0.88-1.03 (m, 2H), −0.04 (s, 9H).
CC(C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-c3nn(C)c4ccc(OC(F)F)cc34)nc12
null
CN(C)C(On1nnc2cccnc21)=[N+](C)C
Cn1nc(-c2cnc3c(n2)c(C(=O)O)cn3COCC[Si](C)(C)C)c2cc(OC(F)F)ccc21
null
CN(C(ON1N=[N:16][C:11]2[CH:12]=CC=N[C:10]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC(N)C.[F:29][CH:30]([F:62])[O:31][C:32]1[CH:33]=[C:34]2[C:38](=[CH:39][CH:40]=1)[N:37]([CH3:41])[N:36]=[C:35]2[C:42]1[N:43]=[C:44]2[C:50]([C:51]([OH:53])=O)=[CH:49][N:48]([CH2:54][O:55][CH2:56][CH2:57][Si:58]([CH3:61])([CH3:60])[CH3:59])[C:45]2=[N:46][CH:47]=1>CN(C=O)C>[F:62][CH:30]([F:29])[O:31][C:32]1[CH:33]=[C:34]2[C:38](=[CH:39][CH:40]=1)[N:37]([CH3:41])[N:36]=[C:35]2[C:42]1[N:43]=[C:44]2[C:50]([C:51]([NH:16][CH:11]([CH3:12])[CH3:10])=[O:53])=[CH:49][N:48]([CH2:54][O:55][CH2:56][CH2:57][Si:58]([CH3:59])([CH3:60])[CH3:61])[C:45]2=[N:46][CH:47]=1
15
CC(C)N
CN(C)C=O
null
25
100
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,270,331
[Li]O
null
null
null
ord_dataset-d3580a12b15e46cc91aa73f4f1a4a8cc
2013-01-01T00:03:00
true
A solution of ethyl[5-{[2-({4-[(diethoxyphosphoryl)methyl]-2-methoxyphenyl}amino)-5-(trifluoromethyl)pyrimidin-4-yl]amino}-3-methyl-4-oxoquinolin-1(4H)-yl]acetate (Example 300, 41 mg, 0.061 mmol) in MeOH (0.5 mL), and THF (0.5 mL) was charged with LiOH H2O (25.6 mg, 0.61 mmol). The resulting mixture was stirred at room temperature for 5 h. The reaction mixture was concentrated under reduced pressure. The material was purified by prep TLC (5% MeOH in DCM) to give 24.1 mg of the desired product (yield: 61%). 1H NMR (DMSO-d6, 400 MHz): δ=1.20 (m, 6H), 1.99 (s, 3H), 3.24 (d, J=21.2 Hz, 2H), 3.78 (s, 3H), 3.99 (m, 2H), 6.90 (d, 1H), 7.03 (s, 1H), 7.43 (s, br, 1H), 7.61 (d, J=7.2 Hz, 1H), 7.94 (s, br, 1H). 8.36 (s, 1H), 8.51-8.56 (m, 2H). MS (ES+): m/z 651.19 [MH+]. HPLC: tR=1.32 min (UPLC TOF, polar—3 min).
CCOP(=O)(Cc1ccc(Nc2ncc(C(F)(F)F)c(Nc3cccc4c3c(=O)c(C)cn4CC(=O)O)n2)c(OC)c1)OCC
null
CCOC(=O)Cn1cc(C)c(=O)c2c(Nc3nc(Nc4ccc(CP(=O)(OCC)OCC)cc4OC)ncc3C(F)(F)F)cccc21
null
null
C([O:3][C:4](=[O:47])[CH2:5][N:6]1[C:15]2[C:10](=[C:11]([NH:16][C:17]3[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][N:20]=[C:19]([NH:27][C:28]4[CH:33]=[CH:32][C:31]([CH2:34][P:35]([O:40][CH2:41][CH3:42])([O:37][CH2:38][CH3:39])=[O:36])=[CH:30][C:29]=4[O:43][CH3:44])[N:18]=3)[CH:12]=[CH:13][CH:14]=2)[C:9](=[O:45])[C:8]([CH3:46])=[CH:7]1)C.C1COCC1.O[Li].O>CO>[CH2:41]([O:40][P:35]([CH2:34][C:31]1[CH:32]=[CH:33][C:28]([NH:27][C:19]2[N:18]=[C:17]([NH:16][C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:10]=3[C:9](=[O:45])[C:8]([CH3:46])=[CH:7][N:6]4[CH2:5][C:4]([OH:47])=[O:3])[C:22]([C:23]([F:24])([F:26])[F:25])=[CH:21][N:20]=2)=[C:29]([O:43][CH3:44])[CH:30]=1)([O:37][CH2:38][CH3:39])=[O:36])[CH3:42]
5
O
CO
C1CCOC1
25
null
60.8
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
367,383
[H-]
[Na+]
null
null
ord_dataset-b18df02d6e9345faa0f2dae281a0870a
1997-01-01T00:06:00
true
In a manner similar to that described above, 3,3-bis(chloromethyl) oxetane (155 g, 1 mole) was reacted with 2,2,3,3,4,4,4-heptafluorobutan-1ol (402 g, 2.01 moles) in DMF (2 L) in the presence of sodium hydride (100 g of 50% dispersion in mineral oil, 2.3 moles) at 85° C. for 16 h to give 340 g (70%) of 3,3-bis(2,2,3,3,4,4,4-heptafluorobutoxymethyl) oxetane, a clear, colorless liquid. Glc analysis revealed the purity of this material to be in excess of 99%: BP=70°-72° C./1.0-1.3 mm-hG; 1H NMR (CDCl3) δ 4.44 (s, 4H), 3.97 (t, J=13.2 Hz), 3.86 (s, 4H); 13cNMR δ 43.9, 68.1 (t), 73.5, and 75.6 (Signals from carbons bearing fluorine are not included due to the complex splitting patterns and overlap of signals); 19fNMR δ -81.6 (3 F), -121.0 (2 F) and -128.3 (2 F); Anal. Calcd for C13H12F14O3 : C, 32.4; H, 2.5. Found: C, 32.3; H, 2.3.
FC(F)(F)C(F)(F)C(F)(F)COCC1(COCC(F)(F)C(F)(F)C(F)(F)F)COC1
null
OCC(F)(F)C(F)(F)C(F)(F)F
ClCC1(CCl)COC1
null
Cl[CH2:2][C:3]1([CH2:7]Cl)[CH2:6][O:5][CH2:4]1.[F:9][C:10]([F:20])([C:13]([F:19])([F:18])[C:14]([F:17])([F:16])[F:15])[CH2:11][OH:12].[H-].[Na+]>CN(C=O)C>[F:9][C:10]([F:20])([C:13]([F:18])([F:19])[C:14]([F:15])([F:16])[F:17])[CH2:11][O:12][CH2:2][C:3]1([CH2:7][O:12][CH2:11][C:10]([F:9])([F:20])[C:13]([F:18])([F:19])[C:14]([F:15])([F:17])[F:16])[CH2:6][O:5][CH2:4]1
null
CN(C)C=O
null
null
null
null
70.5
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,590,377
N#Cc1cc([C@]23CO[C@@H](COCc4ccccc4)C[C@H]2CSC(N)=N3)c(F)cc1F
null
null
null
ord_dataset-e8c6a25568b64529b960953990e6921f
2015-01-01T00:06:00
true
N-[(4aR,6R,8aS)-8a-(5-Cyano-2,4-difluorophenyl)-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C14) was converted to the product using the method described for the synthesis of 5-[(4aR,6R,8aS)-2-amino-6-[(benzyloxy)methyl]-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-2,4-difluorobenzonitrile (2) in Example 2. Yield: 67.0 mg, 0.197 mmol, 88%. LCMS m/z 342.2 [M+H+]. 1H NMR (400 MHz, CD3OD), δ 7.64 (t, J=7.9 Hz, 1H), 7.31 (dd, J=12.1, 9.2 Hz, 1H), 4.41-4.48 (m, 1H), 4.29-4.36 (m, 1H), 4.04 (dd, J=11, 2.4 Hz, 1H), 3.83-3.93 (m, 1H), 3.69 (d, J=11.1 Hz, 1H), 2.86-2.97 (m, 2H), 2.69-2.73 (m, 1H), 1.82 (qd, J=12.4, 2.7 Hz, 1H), 1.52 (ddd, J=13.2, 4.2, 2.5 Hz, 1H).
N#Cc1cc([C@]23CO[C@@H](CF)C[C@H]2CSC(N)=N3)c(F)cc1F
null
N#Cc1cc([C@]23CO[C@@H](CF)C[C@H]2CSC(NC(=O)c2ccccc2)=N3)c(F)cc1F
null
null
[C:1]([C:3]1[C:4]([F:31])=[CH:5][C:6]([F:30])=[C:7]([C@:9]23[CH2:18][O:17][C@@H:16]([CH2:19][F:20])[CH2:15][C@H:14]2[CH2:13][S:12][C:11]([NH:21]C(=O)C2C=CC=CC=2)=[N:10]3)[CH:8]=1)#[N:2].NC1SC[C@@H]2C[C@H](COCC3C=CC=CC=3)OC[C@]2(C2C(F)=CC(F)=C(C=2)C#N)N=1>>[NH2:21][C:11]1[S:12][CH2:13][C@@H:14]2[CH2:15][C@H:16]([CH2:19][F:20])[O:17][CH2:18][C@:9]2([C:7]2[C:6]([F:30])=[CH:5][C:4]([F:31])=[C:3]([CH:8]=2)[C:1]#[N:2])[N:10]=1
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
1,472,513
O=C([O-])[O-]
[K+]
null
null
ord_dataset-fd1fa959d6264608b0b7fcda16741bfd
2014-01-01T00:08:00
true
To a solution of 5-bromo-2,3-difluorophenol (Avocado, 2.5 g, 12.0 mmol) in DMF (50 mL) was added ethyl 4-bromobutyrate (2.57 g, 13.2 mmol) and K2CO3 (2.5 g, 18 mmol). The reaction mixture was heated at 80° C. for 3 hours. The reaction mixture was diluted with EtOAc and washed with water (3×) and brine, dried (MgSO4) and concentrated under vacuum affording the title compound as a colorless oil (3.53 g, 91%). 1H NMR (DMSO-d6, 300 MHz) δ 7.36 (m, 1H), 7.28 (m, 1H), 4.16-4.03 (m, 4H), 2.45 (t, 2H), 2.03-1.94 (m, 2H), 1.18 (t, 3H). LC/MS (Method B): 323.1, 325.0 (M+H)+. HPLC (Method A) Rt 4.94 min (Purity: 99.8%).
CCOC(=O)CCCOc1cc(Br)cc(F)c1F
null
Oc1cc(Br)cc(F)c1F
CCOC(=O)CCCBr
null
[Br:1][C:2]1[CH:3]=[C:4]([F:10])[C:5]([F:9])=[C:6]([OH:8])[CH:7]=1.Br[CH2:12][CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([F:10])[C:5]([F:9])=[C:6]([CH:7]=1)[O:8][CH2:12][CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16]
null
CCOC(C)=O
CN(C)C=O
null
80
91
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
319,239
Cl
null
null
null
ord_dataset-0c61835e3a0b4986aabf2b61b708e322
1995-01-01T00:11:00
true
2-Chloroethanesulfonyl chloride (0.035 ml, 54.6 mg, 0.33 mmol) in methylene chloride (3 ml) was cooled in an ice bath under nitrogen. A solution of 1-(2-methoxy-4-(4-piperidyloxy)phenylacetyl)-4-(2-methylphenyl)-piperazine-2-carboxamide dihydrochloride (149 mg, 0.28 mmol) and diisopropylethylamine (0.243 ml, 0.18 g, 1.4 mmol) in methylene chloride (3 ml) was added dropwise and the mixture was stirred in the cold for 18 hours. The mixture was concentrated in vacuo and the residue chromatographed on silica gel eluted with 3% methanol in methylene chloride. The combined product fractions were evaporated to dryness in vacuo to give 1-(2-methoxy-4-(1-ethenylsulfonyl-4-piperidyloxy)phenylacetyl)-4-(2-methylphenyl)piperazine-2-carboxamide.
C=CS(=O)(=O)N1CCC(Oc2ccc(CC(=O)N3CCN(c4ccccc4C)CC3C(N)=O)c(OC)c2)CC1
null
COc1cc(OC2CCNCC2)ccc1CC(=O)N1CCN(c2ccccc2C)CC1C(N)=O
O=S(=O)(Cl)CCCl
null
Cl[CH2:2][CH2:3][S:4](Cl)(=[O:6])=[O:5].Cl.Cl.[CH3:10][O:11][C:12]1[CH:17]=[C:16]([O:18][CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH:15]=[CH:14][C:13]=1[CH2:25][C:26]([N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH3:40])[CH2:30][CH:29]1[C:41]([NH2:43])=[O:42])=[O:27].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH3:10][O:11][C:12]1[CH:17]=[C:16]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([S:4]([CH:3]=[CH2:2])(=[O:6])=[O:5])[CH2:21][CH2:20]2)[CH:15]=[CH:14][C:13]=1[CH2:25][C:26]([N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH3:40])[CH2:30][CH:29]1[C:41]([NH2:43])=[O:42])=[O:27]
18
ClCCl
CCN(C(C)C)C(C)C
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null
null