mrachilles/ChemistryForwardReaction · Datasets at Hugging Face

868,025

1,423,927

[Cl-]

[H-]

[Na+]

null

ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f

2014-01-01T00:04:00

true

NaH (18.35 mg, 0.76 mmol) was stirred in dry THF (1 ml) at 0° C. and 2-bromo-3-(4-methoxyphenyl)-1H-indole (210 mg, 0.69 mmol) dissolved in dry THF (4.5 ml) was added dropwise. The mixture was stirred at 0° C. for 5 min and then 2,2-bis-(4-cyanatophenyl)propane (251 mg, 0.90 mmol) dissolved in dry THF (4.5 ml) was added dropwise. Water was added and this mixture was stirred for 30 min Brine was added and the aqueous mixture was extracted with DCM. The solvent was concentrated and the crude product was purified on silica (EtOAc/n-Heptane 1:4). 198 mg 2-bromo-3-(4-methoxyphenyl)-1H-indole-1-carbonitrile was obtained.

COc1ccc(-c2c(Br)n(C#N)c3ccccc23)cc1

null

CC(C)(c1ccc(OC#N)cc1)c1ccc(OC#N)cc1

COc1ccc(-c2c(Br)[nH]c3ccccc23)cc1

null

[H-].[Na+].[Br:3][C:4]1[NH:5][C:6]2[C:11]([C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2.O(C1C=CC(C(C2C=CC(OC#N)=CC=2)(C)C)=CC=1)[C:22]#[N:23].O>C1COCC1.[Cl-].[Na+].O>[Br:3][C:4]1[N:5]([C:22]#[N:23])[C:6]2[C:11]([C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2

0.08

C1CCOC1

O

null

0

null

87.7

452,092

37,678

null

ord_dataset-b0ddd49dad024fc7a23ae6f474f9c52f

1978-01-01T00:03:00

true

Using the method of Example 16, 2-benzyloxy-1,3-propane-diol (18.0 g, 0.1 mole), and 3-methoxybenzaldehyde (13.6 g, 0.1 mole) were reacted to give 26.0 g of oil which was distilled at 1 × 10-4 mm to give 20.2 g of product which distilled at a pot temperature of 200°-206° C. nmr analysis of this product indicated it to contain 37% cis-5-benzyloxy-2-(3-methoxyphenyl)-1,3-dioxane.

COc1cccc(C2OCC(OCc3ccccc3)CO2)c1

null

COc1cccc(C=O)c1

OCC(CO)OCc1ccccc1

null

[CH2:1]([O:8][CH:9]([CH2:12][OH:13])[CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:14][O:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH:19]=O>>[CH2:1]([O:8][CH:9]1[CH2:10][O:11][CH:19]([C:18]2[CH:21]=[CH:22][CH:23]=[C:16]([O:15][CH3:14])[CH:17]=2)[O:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

null

86.6

null

271,097

536,814

null

ord_dataset-1884c7bf3d544afdb8d17b5d41b90a27

2002-01-01T00:03:00

true

In the manner described in example 3, 2-bromophenylacetic acid is condensed with 3,4-difluoroaniline to yield 2-[(3,4-difluorophenyl)amino]phenylacetic acid.

O=C(O)Cc1ccccc1Nc1ccc(F)c(F)c1

null

Nc1ccc(F)c(F)c1

O=C(O)Cc1ccccc1Br

null

Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=[O:10].[F:12][C:13]1[CH:14]=[C:15]([CH:17]=[CH:18][C:19]=1[F:20])[NH2:16]>>[F:12][C:13]1[CH:14]=[C:15]([NH:16][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[CH2:8][C:9]([OH:11])=[O:10])[CH:17]=[CH:18][C:19]=1[F:20]

null

525,748

1,655,046

CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC

null

ord_dataset-42cd9bc5aae3485f9a58f1527bd3abf0

2015-01-01T00:11:00

true

To a toluene (112 mL) solution of the compound (5.87 g) obtained in Example 9-(1), Burgess reagent (5.322 g) was added and the mixture was heated under reflux for 2.5 hours. The reaction mixture was concentrated to give a crude product, which was further purified by silica gel chromatography (AcOEt/hexane) to give the titled compound (4.151 g, colorless amorphous.)

CC(C)(C)OC(=O)N1CCC[C@H]1c1nnc(CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)o1

null

CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)NNC(=O)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C

null

[Si:1]([O:18][CH2:19][C:20]([NH:22][NH:23][C:24]([C@@H:26]1[CH2:30][CH2:29][CH2:28][N:27]1[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=O)=[O:21])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C1(C)C=CC=CC=1>[Si:1]([O:18][CH2:19][C:20]1[O:21][C:24]([C@@H:26]2[CH2:30][CH2:29][CH2:28][N:27]2[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=[N:23][N:22]=1)([C:14]([CH3:17])([CH3:15])[CH3:16])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

null

Cc1ccccc1

null

73.2

680,889

179,754

Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1

[C]=O

null

ord_dataset-ed5a3d1f8dc744759e7fa1c320a44e59

1988-01-01T00:11:00

true

0.5 mmoles 1-acetoxy-3-methylthiopropene (Z:E ratio 43:57) and 2.5 mmoles methanol were charged into a 71 cc stainless steel bomb equipped with a glass liner and a Teflon coated stir bar. Ten mole percent, based on 1-acetoxy-3-methylthiopropene, of a catalyst comprising bis(triphenylphosphine)dichloropalladium, (φ3P)2PdCl2, was added. Toluene was included as an internal standard. Five milliliters of tetrahydrofuran as a solvent were also included in the reaction system. The reaction mixture was charged under argon. The bomb was sealed and carbon monoxide at a pressure of 1000 psi (at room temperature) was charged to the bomb, and the bomb was heated to 100° C. and allowed to react for 92.5 hours with stirring. At the termination of the reaction, the reaction products were analyzed by gas chromatography and it was found that 2-acetoxy-4-(methylthio)butanoic acid, methyl ester was produced in a yield of 28.6 percent and that 2-acetoxy-4-(methylthio)thiobutanoic acid, methyl ester was produced in a yield of 19.5 percent, based on the 1-acetoxy-3-methylthiopropene reactant charged. Note that each of the products is hydrolyzable to methionine hydroxy analog.

COC(=S)C(CCSC)OC(C)=O

null

CSCC=COC(C)=O

COC(=O)C(CCSC)OC(C)=O

null

C(OC=CC[S:8]C)(=O)C.CO.[C]=O.[C:14]([O:17][CH:18]([CH2:23][CH2:24][S:25][CH3:26])[C:19]([O:21][CH3:22])=O)(=[O:16])[CH3:15]>O1CCCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1>[C:14]([O:17][CH:18]([CH2:23][CH2:24][S:25][CH3:26])[C:19]([O:21][CH3:22])=[S:8])(=[O:16])[CH3:15]

null

C1CCOC1

CO

Cc1ccccc1

100

19.5

null

828,371

1,452,438

[BH3-]C#N

[Na+]

null

ord_dataset-a86112d52cd54525a5e36d41f18aced2

2014-01-01T00:07:00

true

To a solution of N-(2-aminoethyl)-1-(3,5-dichloropyridin-4-yl)piperidine-4-carboxamide E13 (50 mg, 0.16 mmol) in MeOH (5 mL) was added benzaldehyde (16 μL, 0.16 mmol). After stirring for 2 h, sodium cyanoborohydride (20 mg, 0.32 mmol) was added and the mixture was stirred for a further 20 h. The solvent was removed under reduced pressure, the residue was dissolved in EtOAc (20 mL), washed with a saturated solution of sodium hydrogencarbonate (25 mL), brine (25 mL), dried (MgSO4) and the solvent was removed under reduced pressure. The crude product was purified by preparative tlc on silica gel (CH2Cl2, MeOH, 9:1) to furnish the title compound as a colourless oil (19 mg, 30%), umax (CHCl3)/cm−1 3015, 2850, 1659, 1558, 1512, 1236, 1146, 1036, 934; m/z (ESI) C20H25Cl2N4O requires 407.1400, found [M+H]+ 407.1401.

O=C(NCCNCc1ccccc1)C1CCN(c2c(Cl)cncc2Cl)CC1

null

O=Cc1ccccc1

NCCNC(=O)C1CCN(c2c(Cl)cncc2Cl)CC1

null

[NH2:1][CH2:2][CH2:3][NH:4][C:5]([CH:7]1[CH2:12][CH2:11][N:10]([C:13]2[C:18]([Cl:19])=[CH:17][N:16]=[CH:15][C:14]=2[Cl:20])[CH2:9][CH2:8]1)=[O:6].[CH:21](=O)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C([BH3-])#N.[Na+]>CO>[CH2:21]([NH:1][CH2:2][CH2:3][NH:4][C:5]([CH:7]1[CH2:8][CH2:9][N:10]([C:13]2[C:14]([Cl:20])=[CH:15][N:16]=[CH:17][C:18]=2[Cl:19])[CH2:11][CH2:12]1)=[O:6])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

2

CO

null

30

894,003

428,788

O=C1CCC(=O)N1I

null

ord_dataset-8cce6f317d644b348a7978a2dce3ea01

1999-01-01T00:03:00

true

A solution of 2.94 g (0.010 mol) of 5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid prop-2-ynylamide in 60 ml of acetic acid was treated with 3.36 g (0.015 mol) of N-iodosuccinimide while gassing with argon. After stirring at room temperature for 46 hrs. the dark suspension obtained was completely freed from the solvents and dried azeotropically several times with toluene. The dark brown solid residue was dissolved in 100 ml of THF, treated with 13.7 ml (0.10 mol) of dipropylamine and stirred at room temperature for 3 hrs. The suspension obtained was completely freed from the solvents, the residue was partitioned between ethyl acetate and 1N aqueous hydrochloric acid and extracted. The aqueous-acidic phase was made basic and extracted with ethyl acetate. The organic phase was concentrated, the orange-brownish product was chromatographed over basic Alox (grade III) with dichloromethane/ethyl acetate 4:1 as the eluent and recrystallized from hot isopropyl ether. There was obtained 1.0 g (25%) of 3-(5-dipropylaminomethyl-oxazol-2-yl)-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one as yellowish crystals; m.p. 133°-135°.

CCCN(CCC)Cc1cnc(-c2ncn3c2CN(C)C(=O)c2ccccc2-3)o1

null

CCCNCCC

C#CCNC(=O)c1ncn2c1CN(C)C(=O)c1ccccc1-2

null

[CH2:1]([NH:4][C:5]([C:7]1[N:8]=[CH:9][N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[C:14](=[O:21])[N:13]([CH3:22])[CH2:12][C:11]=12)=[O:6])[C:2]#[CH:3].IN1C(=O)CCC1=O.[CH2:31]([NH:34][CH2:35][CH2:36][CH3:37])[CH2:32][CH3:33]>C(O)(=O)C>[CH2:31]([N:34]([CH2:3][C:2]1[O:6][C:5]([C:7]2[N:8]=[CH:9][N:10]3[C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=4[C:14](=[O:21])[N:13]([CH3:22])[CH2:12][C:11]=23)=[N:4][CH:1]=1)[CH2:35][CH2:36][CH3:37])[CH2:32][CH3:33]

46

CC(=O)O

null

25

null

25.4

369,198

1,516,541

[Cl-]

[NH4+]

null

ord_dataset-8c74302143c04eb9983e4b3a7ead2d72

2014-01-01T00:12:00

true

To a solution of 9-chloro-1-(2,6-dichloro-4-methoxyphenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbaldehyde (146 mg, 0.356 mmol) in tetrahydrofuran (4 mL) was added dropwise ethylmagnesium bromide (3 M solution in diethyl ether, 0.237 mL, 0.711 mmol) at 0° C., and the mixture was stirred at 0° C. for 5 min. The reaction mixture was diluted with aqueous saturated ammonium chloride, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 20-50% ethyl acetate/n-hexane gradient mixture to give the title compound as a colorless solid (137 mg, 0.311 mmol, 87%).

CCC(O)c1ccc(Cl)c2nc3n(c12)CCCN3c1c(Cl)cc(OC)cc1Cl

null

CC[Mg]Br

COc1cc(Cl)c(N2CCCn3c2nc2c(Cl)ccc(C=O)c23)c(Cl)c1

null

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:25]=[O:26])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:15]3[C:20]([Cl:21])=[CH:19][C:18]([O:22][CH3:23])=[CH:17][C:16]=3[Cl:24])[CH2:12][CH2:13][CH2:14][N:7]21.[CH2:27]([Mg]Br)[CH3:28]>O1CCCC1.[Cl-].[NH4+]>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([Cl:24])=[CH:17][C:18]([O:22][CH3:23])=[CH:19][C:20]=4[Cl:21])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:25]([OH:26])[CH2:27][CH3:28])=[CH:4][CH:3]=1

0.08

C1CCOC1

null

0

87.4

null

666,909

130,230

null

ord_dataset-2f37329a4b254471a74f2eb0981f11ec

1985-01-01T00:05:00

true

Prepared analogously to Example 1 from 6-(4-chlorobutoxy)-4,4-dimethyl-4H-3,1-benzoxazin-2-one and 3,4-dimethylthiophenol.

Cc1ccc(SCCCCOc2ccc3c(c2)C(C)(C)OC(=O)N3)cc1C

null

Cc1ccc(S)cc1C

CC1(C)OC(=O)Nc2ccc(OCCCCCl)cc21

null

Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[NH:15][C:14](=[O:16])[O:13][C:12]([CH3:18])([CH3:17])[C:11]=2[CH:19]=1.[CH3:20][C:21]1[CH:22]=[C:23]([SH:28])[CH:24]=[CH:25][C:26]=1[CH3:27]>>[CH3:20][C:21]1[CH:22]=[C:23]([S:28][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[CH:8]=[CH:9][C:10]3[NH:15][C:14](=[O:16])[O:13][C:12]([CH3:18])([CH3:17])[C:11]=3[CH:19]=2)[CH:24]=[CH:25][C:26]=1[CH3:27]

null

702,227

660,962

null

ord_dataset-04d607efe1d9485eb99fafa06880f62e

2005-01-01T00:02:00

true

2,2-Dimethyl-6-formylchromane was condensed with 5-chloro-2-oxindole to give 0.3 g of 5-Chloro-3-(2,2-dimethylchroman-6-ylmethylene)-1,3-dihydroindol-2-one as a yellow-orange solid.

CC1(C)CCc2cc(C=C3C(=O)Nc4ccc(Cl)cc43)ccc2O1

null

O=C1Cc2cc(Cl)ccc2N1

CC1(C)CCc2cc(C=O)ccc2O1

null

[CH3:1][C:2]1([CH3:14])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:12]=O)[CH:8]=2)[O:3]1.[Cl:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[CH2:19]2>>[Cl:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[C:19]2=[CH:12][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[O:3][C:2]([CH3:14])([CH3:1])[CH2:11][CH2:10]2

null

714,564

267,148

null

ord_dataset-134cf2fa32ab464880d75db06c38f35a

1993-01-01T00:05:00

true

The title compound is prepared by the procedure of Example 28 using 0.750 g of product from Example 58 and 12.13 g of methyl iodide. The residue is recrystallized from methyl alcohol to give 0.90 g of the desired product as colorless needles.

CCCCCCCCCCCCCCOc1ccc(C(=O)NCCc2cccc[n+]2C)cc1

[I-]

CCCCCCCCCCCCCCOc1ccc(C(=O)NCCc2ccccn2)cc1

CI

null

[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][NH:9][C:10](=[O:32])[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:13][CH:12]=1.[CH3:33][I:34]>>[I-:34].[CH3:33][N+:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][CH2:8][NH:9][C:10](=[O:32])[C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:15][CH:16]=1

null

90.7

null

721,164

367,885

[Pd]

null

ord_dataset-b18df02d6e9345faa0f2dae281a0870a

1997-01-01T00:06:00

true

A mixture of 3-(N-t-butoxycarbonyl-1,2,5,6-tetrahydropyrid-4-yl)-5-nitro-1H-indole (3.55 g, 10.34 mmol) and 10% palladium on carbon (0.55 g) in absolute ethanol (60 mL) was shaken under a hydrogen atmosphere (3 atm) for 7 hours at room temperature. The resulting reaction mixture was filtered through diatomaceous earth, and the filtrate was evaporated under reduced pressure. The residual solid was triturated in diethyl ether to afford the title compound (2.56 g, 78%) as a pale pink solid: mp, decomposes 215° C.; 13C NMR (CDCl3) δ155.0, 139.0, 131.3, 127.3, 120.4, 119.8, 112.9, 111.8, 104.1, 79.4, 44.5, 33.8, 32.7, 28.5. Anal. calcd. for C18H25N3O2.1.4 H2O: C, 67.57; H, 8.03; N, 13.13. Found: C, 67.20; H, 8.07; N, 13.44.

CC(C)(C)OC(=O)N1CCC(c2c[nH]c3ccc(N)cc23)CC1

null

CC(C)(C)OC(=O)N1CC=C(c2c[nH]c3ccc([N+](=O)[O-])cc23)CC1

null

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([N+:23]([O-])=O)[CH:21]=3)[NH:16][CH:15]=2)=[CH:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>[Pd].C(O)C>[NH2:23][C:20]1[CH:21]=[C:22]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[C:14]2[CH:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]1

7

CCO

null

25

null

78.5

400,516

854,565

Cl

OO

[Na+]

null

ord_dataset-faa0236be76c4501841c954527cd1b6c

2008-01-01T00:12:00

true

A solution of 1-(4-methoxyphenyl)cyclohexanecarbonitrile (E2) (1.092 g, 5.07 mmol) in dioxane (6 ml) to a mixture of 2 M NaOH in water (150 ml) and 30% H2O2 in water (7.5 ml) was added and the resultant suspension was stirred under reflux for 4 days. The pH of the reaction medium was brought to pH 1 with conc. HCl (ca. 30 ml) and the obtained mixture was extracted with ethyl acetate (4×80 ml). The combined organic extract was washed with brine (50 ml) and dried (Na2SO4). The solvent was evaporated and the residue was chromatographed on silicagel (50 g) with benzene-ethyl acetate-acetic acid (9:1:0.15) as eluent affording the title compound (0.844 g, 71%) as a white solid. 1H NMR (CDCl3, HMDSO) δ: 1.05-1.91 (8H, m); 2.16-2.61 (2H, m); 3.76 (3H, s); 6.86 (2H, d, J=9.0 Hz); 7.34 (2H, d, J=9.0 Hz); 11.26 (1H, br s).

COc1ccc(C2(C(=O)O)CCCCC2)cc1

null

O

COc1ccc(C2(C#N)CCCCC2)cc1

[OH-]

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([C:15]#N)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[OH-:17].[Na+].Cl.[OH2:20]>O1CCOCC1.OO>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([C:15]([OH:20])=[O:17])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1

null

C1COCCO1

null

71

68,504

176,175

CSC(=NC#N)SC

NCCCOc1cccc(CN2CCCCC2)c1

null

ord_dataset-07db50a3ce6941919df30a9e2898988f

1988-01-01T00:08:00

true

Similarly prepared from 3-[3-(1-piperidinylmethyl)phenoxy]propanamine] (10 g) and cyanocarbonimidodithioic acid, dimethyl ester (5.84 g) was N'-cyano-N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]carbamimidothioic acid methyl ester (11.5 g) m.p. 89°-90°.

CSC(=NC#N)NCCCOc1cccc(CN(C)C)c1

null

CSC(=NC#N)NCCCOc1cccc(CN2CCCCC2)c1

null

N1(CC2C=C(C=CC=2)OCCCN)CCCCC1.C(N=C(SC)SC)#N.[CH3:27][S:28][C:29](=[N:48][C:49]#[N:50])[NH:30][CH2:31][CH2:32][CH2:33][O:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41][N:42]2[CH2:47]CCC[CH2:43]2)[CH:36]=1>>[C:49]([N:48]=[C:29]([S:28][CH3:27])[NH:30][CH2:31][CH2:32][CH2:33][O:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH2:41][N:42]([CH3:47])[CH3:43])[CH:36]=1)#[N:50]

null

784,359

585,164

CCOC(=O)[C@H](CCc1ccccc1)N[C@@H](C)C(=O)N1Cc2ccccc2C[C@H]1C(=O)O

[Mg+2]

[OH-]

null

ord_dataset-cb5dd7a8b94e4f19a9148a1904b0dcb6

2003-01-01T00:03:00

true

In the liquid mixture, the 10.0 g of quinapril hydrochloride reacted with 1.23 g of magnesium hydroxide to produce 9.47 g of quinapril magnesium plus 1.00 g of magnesium chloride, plus 0.76 g of water. The liquid was then filtered to remove the excess magnesium hydroxide.

[Cl-]

[Mg]

Cl

null

[CH3:1][CH2:2][O:3][C:4]([C@@H:6]([NH:15][C@H:16]([C:18]([N:20]1[C@H:29]([C:30]([OH:32])=[O:31])[CH2:28][C:27]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH2:21]1)=[O:19])[CH3:17])[CH2:7][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)=[O:5].[ClH:33].[OH-].[Mg+2:35].[OH-]>O>[CH3:1][CH2:2][O:3][C:4]([C@@H:6]([NH:15][C@H:16]([C:18]([N:20]1[C@H:29]([C:30]([OH:32])=[O:31])[CH2:28][C:27]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH2:21]1)=[O:19])[CH3:17])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5].[Mg:35].[Cl-:33].[Mg+2:35].[Cl-:33]

null

O

null

180,539

79,274

null

ord_dataset-0c37e633e9814a6e886187796cacf216

1981-01-01T00:03:00

true

2-bromo-6-chlorotoluene (20.55 g) and N-bromosuccinimide (19.6 g) were stirred together in carbon tetrachloride (100 ml) under reflux for 22 hours exposure to radiation from an infrared lamp. The resulting solution was cooled in ice, filtered and evaporated to yield the title product which was dissolved in petroleum ether (60-80). Part was recrystallised therefrom as pink needles (8.5 g) and part was recovered by evaporation as a dark orange solid (17.7 g) (total yield 26.2 g. 92%).

Clc1cccc(Br)c1CBr

null

Cc1c(Cl)cccc1Br

O=C1CCC(=O)N1Br

null

[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH3:9].[Br:10]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH2:9][Br:10]

null

ClC(Cl)(Cl)Cl

null

652,015

934,719

null

ord_dataset-d8a5dc784dde4465894ec7c69d2e3ba6

2010-01-01T00:01:00

true

N-[4-chloro-3-(trifluoromethyl)phenyl]-4-(4-methoxyphenyl)butanamide was prepared as described in Example 5, Step 1 using 4-(4-methoxyphenyl)butyric acid and 4-chloro-3-(trifluoromethyl)aniline. LCMS, AA: Rt=2.17 min, [MH− 370.1].

COc1ccc(CCCC(=O)Nc2ccc(Cl)c(C(F)(F)F)c2)cc1

null

Nc1ccc(Cl)c(C(F)(F)F)c1

COc1ccc(CCCC(=O)O)cc1

null

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O)=[CH:5][CH:4]=1.[Cl:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=1[C:23]([F:26])([F:25])[F:24]>>[Cl:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:12](=[O:14])[CH2:11][CH2:10][CH2:9][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)=[CH:18][C:17]=1[C:23]([F:24])([F:25])[F:26]

null

327,743

1,687,572

null

ord_dataset-c1e70ad912eb438f8d34b1dc681f809a

2016-01-01T00:02:00

true

To a solution of 2-hydroxy-3-methyl-benzoic acid (10 g, 66.7 mmol, 1.0 eq) in acetic acid (100 mL) was added bromine (10.66 g, 66.7 mmol, 1.0 eq) slowly over 5 min. The mixture was stirred at room temperature for 24 h, then water was added slowly and the mixture was stirred for a further 30 min. The precipitate was collected by filtration and was washed with water and dried to give the title compound as a white solid (13.7 g, 90%).

Cc1cc(Br)cc(C(=O)O)c1O

null

BrBr

Cc1cccc(C(=O)O)c1O

null

[OH:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[Br:12]Br.O>C(O)(=O)C>[Br:12][C:8]1[CH:9]=[C:10]([CH3:11])[C:2]([OH:1])=[C:3]([CH:7]=1)[C:4]([OH:6])=[O:5]

24

CC(=O)O

O

null

25

null

88.9

690,799

584,356

null

ord_dataset-cb5dd7a8b94e4f19a9148a1904b0dcb6

2003-01-01T00:03:00

true

Prepared according to the procedure described for Example 60 using 3-amino-4-methoxy-N-phenyl-benzamide (0.976 g, 4.02 mmol) and 4-nitrophenyl isothiocyanate (0.723 g, 4.02 mmol) to afford the product (1.39 g) after trituration in ether; m.p. 183-184° C.

COc1ccc(C(=O)Nc2ccccc2)cc1NC(=S)Nc1ccc([N+](=O)[O-])cc1

null

O=[N+]([O-])c1ccc(N=C=S)cc1

COc1ccc(C(=O)Nc2ccccc2)cc1N

null

[NH2:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[O:17][CH3:18])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:6].[N+:19]([C:22]1[CH:27]=[CH:26][C:25]([N:28]=[C:29]=[S:30])=[CH:24][CH:23]=1)([O-:21])=[O:20]>CCOCC>[CH3:18][O:17][C:16]1[CH:15]=[CH:14][C:4]([C:5]([NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:6])=[CH:3][C:2]=1[NH:1][C:29]([NH:28][C:25]1[CH:24]=[CH:23][C:22]([N+:19]([O-:21])=[O:20])=[CH:27][CH:26]=1)=[S:30]

null

CCOCC

null

81.8

182,931

1,575,689

O=C([O-])[O-]

[Cs+]

null

ord_dataset-9741bb5fd93044078df2a45f45733054

2015-01-01T00:04:00

true

To a solution of Example 227A (0.521 g, 1.91 mmol) in dioxane (10 mL) at ambient temperature was added 2-(t-butyldimethylsilyl)thiophene-5-boronic acid pinacol ester (0.619 g, 1.91 mmol), 2 molar cesium carbonate (0.9 mL, 1.9 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.031 g, 0.038 mmol). The solution was degassed (3× vacuum/purge N2) and heated to 80° C. overnight. The mixture was cooled and partioned between water and CH2Cl2. The organic phase concentrated and the residue triturated with ether to provide 355 mg (41%) of the title compound. MS (DCI30 ) m/z 391 (M+H); 1H NMR (300 MHz, CDCl3) δ 7.69-7.60 (m, 2H), 7.54 (d, J=7.6 Hz, 1H), 7.25 (d, J=3.6 Hz, 1H), 7.12 (d, J=7.4 Hz, 1H), 3.99 (s, 2H), 3.70 (dd, J=10.9, 4.0 Hz, 1H), 3.50 (dd, J=10.9, 6.4 Hz, 1H), 2.51 (td, J=6.5, 4.0 Hz, 1H), 1.92 (td, J=13.6, 6.8 Hz, 1H), 1.06 (d, J=6.8 Hz, 3H), 1.00-0.92 (m, 12H), 0.37-0.28 (m, 6H).

CC(C)[C@H](CO)NCc1cccc(-c2ccc([Si](C)(C)C(C)(C)C)s2)n1

null

CC1(C)OB(c2ccc([Si](C)(C)C(C)(C)C)s2)OC1(C)C

CC(C)[C@H](CO)NCc1cccc(Br)n1

null

Br[C:2]1[N:7]=[C:6]([CH2:8][NH:9][C@H:10]([CH:13]([CH3:15])[CH3:14])[CH2:11][OH:12])[CH:5]=[CH:4][CH:3]=1.[Si:16]([C:23]1[S:24][C:25](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:27]=1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[Si:16]([C:23]1[S:24][C:25]([C:2]2[N:7]=[C:6]([CH2:8][NH:9][C@H:10]([CH:13]([CH3:15])[CH3:14])[CH2:11][OH:12])[CH:5]=[CH:4][CH:3]=2)=[CH:26][CH:27]=1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]

null

C1COCCO1

null

80

null

47.6

825,057

834,637

O=C([O-])[O-]

[K+]

null

ord_dataset-ec576c604a9d47258c87c732a043ec71

2008-01-01T00:08:00

true

A mixture of 1-[2-(4-cyclopropylmethylpiperazin-1-yl)phenyl]-3,3,5,5-tetramethylcyclohexanol (250 mg, 0.675 mmol) produced in Example (108b), water (0.12 mL) and trifluoroacetic acid (1.04 mL, 13.5 mmol) was stirred for 21 hours at an external temperature of room temperature. Aqueous solution of potassium carbonate was added to the reaction mixture and then extraction was performed with ethyl acetate. Organic layer was concentrated under reduced pressure to give a residue, which was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 218 mg of the title compound as a colorless solid.

CC1(C)C=C(c2ccccc2N2CCN(CC3CC3)CC2)CC(C)(C)C1

null

CC1(C)CC(C)(C)CC(O)(c2ccccc2N2CCN(CC3CC3)CC2)C1

null

[CH:1]1([CH2:4][N:5]2[CH2:10][CH2:9][N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[C:17]3(O)[CH2:22][C:21]([CH3:24])([CH3:23])[CH2:20][C:19]([CH3:26])([CH3:25])[CH2:18]3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>O>[CH:1]1([CH2:4][N:5]2[CH2:6][CH2:7][N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[C:17]3[CH2:22][C:21]([CH3:24])([CH3:23])[CH2:20][C:19]([CH3:26])([CH3:25])[CH:18]=3)[CH2:9][CH2:10]2)[CH2:2][CH2:3]1

21

O=C(O)C(F)(F)F

O

null

25

null

91.6

522,180

790,513

O=P([O-])([O-])[O-]

[H-]

[Na+]

null

ord_dataset-530502f8e61e455784f93c5faa45c94b

2007-01-01T00:09:00

true

Sodium hydride (60% dispersion in mineral oil, 145 mg) was added portionwise to a solution of 4-(2-hydroxyethyl)phenol (502 mg) in THF (15 ml) and the mixture was stirred at 20° C. for 30 min. tert-Butyldimethylsilyl chloride (547 mg) was added and the mixture was stirred for 75 min. Phosphate buffer solution (pH 6.5) was added and the mixture was extracted with EtOAc. The combined extracts were dried (Na2SO4) and the solvent evaporated in vacuo to give a residue which was purified by SPE (10 g). Elution with DCM-cyclohexane (1:3) then DCM then EtOAc gave the title compound (658 mg). LCMS RT=3.62 min.

CC(C)(C)[Si](C)(C)Oc1ccc(CCO)cc1

null

CC(C)(C)[Si](C)(C)Cl

OCCc1ccc(O)cc1

null

[H-].[Na+].[OH:3][CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=1.[Si:13](Cl)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].P([O-])([O-])([O-])=O>C1COCC1>[Si:13]([O:12][C:9]1[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][OH:3])=[CH:7][CH:8]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]

1.25

C1CCOC1

null

71.8

null

646,556

1,754,512

CC(=O)O[BH-](OC(C)=O)OC(C)=O

Cl

[Na+]

null

ord_dataset-97eb2ab57fec4160922caae33b54d956

2016-01-01T00:08:00

true

Sodium triacetoxyborohydride (0.30 g, 1.4 mmol) was added to a solution of 5-(tert-butyl)-2-hydroxy-3-(6-(trifluoromethyl)pyridin-3-yl)benzaldehyde (0.35 g, 1.1 mmol) and 1-methyl piperazine (0.14 mL, 1.3 mmol) in tetrahydrofuran (10 mL). The reaction mixture was stirred at room temperature under nitrogen for 16 hours. The reaction was partitioned between ethyl acetate (25 mL) and saturated aqueous sodium bicarbonate solution (25 mL). The organic phase was dried with sodium sulfate, filtered and concentrated under reduced pressure to give a yellow syrup. The product was purified using flash chromatography on silica eluting with a solvent gradient of 0 to 100% ethyl acetate in hexanes to give a yellow syrup which was dissolved in 1.25 M hydrochloric acid in ethanol (10 mL, 12.5 mmol). The mixture stood for 20 minutes and was then concentrated under reduced pressure to give a white solid which was triturated with diethyl ether (10 mL) and solid was filtered off to afford 4-(tert-butyl)-2-((4-methylpiperazin-1-yl)methyl)-6-(6-(trifluoromethyl)pyridin-3-yl)phenol dihydrochloride (0.26 g, 53% yield) as a white solid.

CN1CCN(Cc2cc(C(C)(C)C)cc(-c3ccc(C(F)(F)F)nc3)c2O)CC1

null

CC(C)(C)c1cc(C=O)c(O)c(-c2ccc(C(F)(F)F)nc2)c1

CN1CCNCC1

null

C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:15]([C:19]1[CH:20]=[C:21]([C:28]2[CH:29]=[N:30][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:32][CH:33]=2)[C:22]([OH:27])=[C:23]([CH:26]=1)[CH:24]=O)([CH3:18])([CH3:17])[CH3:16].[CH3:38][N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1.C(O)C.[ClH:48]>O1CCCC1>[ClH:48].[ClH:48].[C:15]([C:19]1[CH:20]=[C:21]([C:28]2[CH:29]=[N:30][C:31]([C:34]([F:36])([F:37])[F:35])=[CH:32][CH:33]=2)[C:22]([OH:27])=[C:23]([CH2:24][N:42]2[CH2:43][CH2:44][N:39]([CH3:38])[CH2:40][CH2:41]2)[CH:26]=1)([CH3:16])([CH3:18])[CH3:17]

16

CCO

C1CCOC1

null

25

53

null

885,127

308,913

CCN=C=NCCCN(C)C

Cl

null

ord_dataset-acbdbaa766314b66a982823354e82bf2

1995-01-01T00:04:00

true

A solution of ethyl 2-ethyl-3-[2'-(t-butoxycarbonyl)biphenyl-4-yl]methyl-4,5,6,7-tetrahydroimidazo[4,5-c]pyridine-4-carboxylate (1.72 g), monoethyl malonate (0.94 g), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.02 g), triethylamine (1.78 g) in dichloromethane (20 ml) is stirred overnight at room temperature. The reaction mixture is washed with water and dried over sodium sulfate and then evaporated. The residue is purified by silica gel column chromatography (solvent; chloroform/methanol) to give ethyl 2-ethyl-3-[2'-(t-butoxycarbonyl)biphenyl-4-yl]methyl-5-ethoxycarbonylacetyl-4,5,6,7-tetrahydroimidazo[4,5-c]pyridine-4-carboxylate (1.57 g) as an oil.

CCOC(=O)CC(=O)N1CCc2nc(CC)n(Cc3ccc(-c4ccccc4C(=O)OC(C)(C)C)cc3)c2C1C(=O)OCC

null

CCOC(=O)CC(=O)[O-]

CCOC(=O)C1NCCc2nc(CC)n(Cc3ccc(-c4ccccc4C(=O)OC(C)(C)C)cc3)c21

null

[CH2:1]([C:3]1[N:16]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:20][CH:19]=2)[C:6]2[CH:7]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:8][CH2:9][CH2:10][C:5]=2[N:4]=1)[CH3:2].[C:37]([O:43][CH2:44][CH3:45])(=[O:42])[CH2:38][C:39]([O-])=[O:40].Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>ClCCl>[CH2:1]([C:3]1[N:16]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]([O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:31])=[CH:22][CH:23]=2)[C:6]2[CH:7]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:8]([C:39](=[O:40])[CH2:38][C:37]([O:43][CH2:44][CH3:45])=[O:42])[CH2:9][CH2:10][C:5]=2[N:4]=1)[CH3:2]

null

CCN(CC)CC

ClCCl

null

74

null

651,508

1,289,836

null

ord_dataset-d5c54236ecd94d61aaa071461bcfc426

2013-01-01T00:04:00

true

To a cooled (−20° C.) solution of tert-butyl 4-[4-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-1,3-thiazol-2-yl]piperidine-1-carboxylate (914 mg. 2.28 mmol) in DMF (12.6 mL) and AcOH (5 mL) was added 1,3-dibromo-5,5-dimethylhydantoin (326 mg, 1.14 mmol) in 3 portions over 10 minutes. The mixture was stirred at 0° C. for 3 h. The reaction was quenched with the addition 5% aqueous K2CO3 (50 mL) and was allowed to warm to rt. The mixture was extracted with ethyl acetate (3×50 mL). The combined organics were washed with brine, dried (Na2SO4) and evaporated. The crude material was purified by ISCO® chromatography using a gradient of 50% to 75% ethyl acetate in hexanes to afford 596 mg (54%) of the desired product. ES-MS m/z 480.85 [M+H]+, HPLC RT (min) 3.45.

CC(C)(C)OC(=O)N1CCC(c2nc(-c3cc(Br)c4c(N)ncnn34)cs2)CC1

null

CC(C)(C)OC(=O)N1CCC(c2nc(-c3ccc4c(N)ncnn34)cs2)CC1

CC1(C)C(=O)N(Br)C(=O)N1Br

null

[NH2:1][C:2]1[C:7]2=[CH:8][CH:9]=[C:10]([C:11]3[N:12]=[C:13]([CH:16]4[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]4)[S:14][CH:15]=3)[N:6]2[N:5]=[CH:4][N:3]=1.[Br:29]N1C(C)(C)C(=O)N(Br)C1=O>CN(C=O)C.CC(O)=O>[NH2:1][C:2]1[C:7]2=[C:8]([Br:29])[CH:9]=[C:10]([C:11]3[N:12]=[C:13]([CH:16]4[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]4)[S:14][CH:15]=3)[N:6]2[N:5]=[CH:4][N:3]=1

3

CC(=O)O

CN(C)C=O

null

0

null

109.1

784,660

1,583,993

[K+]

[OH-]

null

ord_dataset-380e279f82154dba9e08ab51b3bdd08a

2015-01-01T00:05:00

true

To a solution of 2-tosyl-1H-indole (199 mg, 0.73 mmol) in 3 mL DMF was added 1,4-dibromobutane (263 μL, 2.20 mmol) in 1 mL DMF and KOH (41 mg, 0.73 mmol), and the reaction stirred at room temperature 1.75 h. The reaction mixture was then partitioned between water and ether, and the aqueous layer extracted twice with ether. The combined organic extract was washed with water, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified via silica gel chromatography using a gradient from 0 to 15% ethyl acetate in hexanes to give a final yield of 178 mg (0.44 mmol). 1H NMR (500 MHz, CDCl3, δ): 1.66-1.81 (m, 2H), 1.81-1.94 (m, 2H), 2.44 (s, 3H), 3.34 (t, J=6.4 Hz, 2H), 4.35 (t, J=7.6 Hz, 2H), 7.21 (t, J=7.0 Hz, 1H), 7.30-7.44 (m, 5H), 7.73 (d, J=7.9 Hz, 1H), 7.87 (d, J=8.1 Hz, 2H). 13C NMR (500 MHz, CDCl3, δ): 22.07, 29.04, 30.26, 33.26, 44.41, 111.08, 111.49, 121.67, 123.42, 125.83, 126.19, 128.09, 130.44, 135.22, 138.78, 139.12, 145.08. MS m/z 406.3 [M+H]+.

Cc1ccc(S(=O)(=O)c2cc3ccccc3n2CCCCBr)cc1

null

BrCCCCBr

Cc1ccc(S(=O)(=O)c2cc3ccccc3[nH]2)cc1

null

[S:1]([C:11]1[NH:12][C:13]2[C:18]([CH:19]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[Br:20][CH2:21][CH2:22][CH2:23][CH2:24]Br.[OH-].[K+]>CN(C=O)C>[Br:20][CH2:21][CH2:22][CH2:23][CH2:24][N:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:19]=[C:11]1[S:1]([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:2])=[O:3]

1.75

CN(C)C=O

null

25

null

447,776

756,682

Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1

I[Cu]I

null

ord_dataset-1b0cd79134f0450eaac8396a4f956c30

2007-01-01T00:02:00

true

3-Iodo-6-{2-[2-(4-trifluoromethyl-phenyl)-vinyl]-oxazol-4-ylmethoxy}-pyridazine (0.114 g, 0.25 mmol), 1-but-3-ynyl-1H-[1,2,3]triazole (0.040 g, 0.30 mmol) and triethyl amine (NEt3) (0.125 ml) are dissolved in THF (1 ml) and copper iodide (CuI) (0.0048 g, 0.025 mmol) is added under stirring. After passing a stream of argon through the mixture for 10 min bis(triphenylphosphine)palladium(II) dichloride (0.088 g, 0.0125 mmol) is added and stirring is continued for 3 h at r.t. Ethyl acetate (30 ml) is added; the mixture is washed with saturated ammonium chloride (NH4Cl) and brine, dried over MgSO4 and concentrated in vacuo. The crude product is purified by flash column chromatography (ethyl acetate/hexanes 1:3->ethyl acetate (100%)) yielding 3-(4-[1,2,3]triazol-1-yl-but-1-ynyl)-6-{2-[2-(4-trifluoromethyl-phenyl)-vinyl]-oxazol-4-ylmethoxy}-pyridazine as a colorless solid. Yield 93 mg (64%).

FC(F)(F)c1ccc(C=Cc2nc(COc3ccc(C#CCCn4ccnn4)nn3)co2)cc1

null

C#CCCn1ccnn1

FC(F)(F)c1ccc(C=Cc2nc(COc3ccc(I)nn3)co2)cc1

null

I[C:2]1[N:3]=[N:4][C:5]([O:8][CH2:9][C:10]2[N:11]=[C:12]([CH:15]=[CH:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)[O:13][CH:14]=2)=[CH:6][CH:7]=1.[CH2:27]([N:31]1[CH:35]=[CH:34][N:33]=[N:32]1)[CH2:28][C:29]#[CH:30].C(N(CC)CC)C.C(OCC)(=O)C>C1COCC1.[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:31]1([CH2:27][CH2:28][C:29]#[C:30][C:2]2[N:3]=[N:4][C:5]([O:8][CH2:9][C:10]3[N:11]=[C:12]([CH:15]=[CH:16][C:17]4[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=4)[O:13][CH:14]=3)=[CH:6][CH:7]=2)[CH:35]=[CH:34][N:33]=[N:32]1

3

CCOC(C)=O

CCN(CC)CC

C1CCOC1

null

145,828

642,872

CCN=C=NCCCN(C)C

Cl

On1nnc2ccccc21

null

ord_dataset-ce71a906ea9c4399a2014cbaaff88c8f

2004-01-01T00:07:00

true

4-[4-(4-tert-Butylphenyl)-4-oxo-2-(4-trifluoromethoxyphenyl)butyryl]benzoic acid (10.4 g, 20.86 mmol) was dissolved in DMF (150 mL) and added EDAC (5.60 g, 29.20) and HOBt (4.23 g, 31.29 mmol). After ½ h a solution of beta-alanine methyl ester hydrochloride (4.37 g, 31.29 mmol) and DIPEA (5.36 mL, 31.29 mmol) in DMF (20 mL) was added to the above mixture and the reaction mixture was stirred night over. The reaction was concentrated to approximately 100 mL and diluted with water (200 mL) and extracted with ethyl acetate (200 mL). The water phase was extracted with additional ethyl acetate (75 mL). The combined organic phases were washed with hydrochloric acid (0.2 N, 3×150 mL), aqueous sodium chloride (50% saturation, 3×150 mL) and dried over magnesium sulphate. The dried organic phase was filtered and evaporated to dryness to afford 3-{4-[4-(4-tert-butylphenyl)-4-oxo-2-(4-trifluoromethoxyphenyl)butyryl]benzoylamino}propionic acid methyl ester (12.76 g).

COC(=O)CCNC(=O)c1ccc(C(=O)C(CC(=O)c2ccc(C(C)(C)C)cc2)c2ccc(OC(F)(F)F)cc2)cc1

null

COC(=O)CCN

CC(C)(C)c1ccc(C(=O)CC(C(=O)c2ccc(C(=O)O)cc2)c2ccc(OC(F)(F)F)cc2)cc1

null

[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11](=[O:36])[CH2:12][CH:13]([C:25]2[CH:30]=[CH:29][C:28]([O:31][C:32]([F:35])([F:34])[F:33])=[CH:27][CH:26]=2)[C:14]([C:16]2[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=2)=[O:15])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.[CH3:59][O:60][C:61](=[O:65])[CH2:62][CH2:63][NH2:64].CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:59][O:60][C:61](=[O:65])[CH2:62][CH2:63][NH:64][C:20](=[O:21])[C:19]1[CH:23]=[CH:24][C:16]([C:14](=[O:15])[CH:13]([C:25]2[CH:26]=[CH:27][C:28]([O:31][C:32]([F:33])([F:35])[F:34])=[CH:29][CH:30]=2)[CH2:12][C:11]([C:8]2[CH:9]=[CH:10][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][CH:7]=2)=[O:36])=[CH:17][CH:18]=1

null

CN(C)C=O

CCN(C(C)C)C(C)C

null

104.8

485,880

648,473

null

ord_dataset-5d77a731aa10488794c824ad12021f57

2004-01-01T00:09:00

true

Prepared from 6-methoxy-2-indolinone (prepared according to Quallich, G. J.; Morrissey, P. M.; Synthesis 1993, 51) and acetic anhydride

COc1ccc2c(c1)N(C(C)=O)C(=O)C2

null

CC(=O)OC(C)=O

COc1ccc2c(c1)NC(=O)C2

null

[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][C:8](=[O:12])[NH:9]2)=[CH:5][CH:4]=1.[C:13](OC(=O)C)(=[O:15])[CH3:14]>>[C:13]([N:9]1[C:10]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:11]=2)[CH2:7][C:8]1=[O:12])(=[O:15])[CH3:14]

null

265,549

257,499

CC#CCOC(=N)C(Cl)(Cl)Cl

O=S(=O)(O)C(F)(F)F

null

ord_dataset-2369b9b9f44641b1930518c59ae89a95

1992-01-01T00:11:00

true

To a solution of 17-ethyl-1,14-dihydroxy-12-[2'-(4",3"-dihydroxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (50 mg in 1.5 ml 33% methylene chloride in cyclohexane) is added 2-butynyl trichloroacetimidate (20 μl neat) and the reagents are allowed to mix for 5 minutes. Trifluoromethanesulfonic acid (2 μl neat) is added slowly via syringe and the mixture stirred at room temperature. After 16 hours the reaction is quenched by the addition of saturated sodium bicarbonate and extracted with ethyl acetate (3×5 ml). The combined organics are washed with brine and dried over magnesium sulfate. Purification of the concentrate by preparative TLC on silica gel gives the title compound.

CC#CCOC1CCC(C=C(C)C2OC(=O)C3CCCCN3C(=O)C(=O)C3(O)OC(C(OC)CC(C)CC(C)=CC(CC)C(=O)CC(O)C2C)C(OC)CC3C)CC1O

null

CCC1C=C(C)CC(C)CC(OC)C2OC(O)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C)=CC3CCC(O)C(O)C3)C(C)C(O)CC1=O)C(C)CC2OC

null

[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:52])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([OH:50])[CH:46]([OH:51])[CH2:45]2)[CH:7]([CH3:53])[CH:6]([OH:54])[CH2:5][C:4]1=[O:55])[CH3:2].FC(F)(F)S(O)(=O)=O>ClC(Cl)(Cl)C(=N)OCC#CC>[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:52])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([O:50][CH2:2][C:1]#[C:3][CH3:4])[CH:46]([OH:51])[CH2:45]2)[CH:7]([CH3:53])[CH:6]([OH:54])[CH2:5][C:4]1=[O:55])[CH3:2]

null

25

null

676,138

1,741,733

C[C@@H](Oc1nc(-c2ccc(N3CCN(C(=O)OC(C)(C)C)CC3)c(F)c2)cc2ncn(C3CC3)c12)[C@H]1CNC(=O)C1

null

ord_dataset-eacfee6d16d8455a93348409f1b37be4

2016-01-01T00:06:00

true

Following the procedure described for intermediate from Step-3 in Example 3.100, starting from combined (R)-4-((R)-1-((5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one (250 mg, 0.69 mmol) and tert-butyl 4-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate (348.59 mg, 0.86 mmol) (B11), 250 mg tert-butyl 4-(4-(3-cyclopropyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-2-fluorophenyl)piperazine-1-carboxylate was synthesized.

C[C@@H](Oc1cc(-c2ccc(N3CCN(C(=O)OC(C)(C)C)CC3)c(F)c2)cc2ncn(C3CC3)c12)[C@H]1CNC(=O)C1

null

CC(C)(C)OC(=O)N1CCN(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2F)CC1

C[C@@H](Oc1cc(Br)cc2ncn(C3CC3)c12)[C@H]1CNC(=O)C1

null

Br[C:2]1[CH:13]=[C:12]([O:14][C@@H:15]([C@H:17]2[CH2:21][NH:20][C:19](=[O:22])[CH2:18]2)[CH3:16])[C:5]2[N:6]([CH:9]3[CH2:11][CH2:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1.[F:23][C:24]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[CH:26][C:25]=1[N:39]1[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41][CH2:40]1.C1(N2C3C(O[C@@H]([C@@H]4CC(=O)NC4)C)=NC(C4C=CC(N5CCN(C(OC(C)(C)C)=O)CC5)=C(F)C=4)=CC=3N=C2)CC1>>[CH:9]1([N:6]2[C:5]3[C:12]([O:14][C@@H:15]([C@@H:17]4[CH2:18][C:19](=[O:22])[NH:20][CH2:21]4)[CH3:16])=[CH:13][C:2]([C:28]4[CH:27]=[CH:26][C:25]([N:39]5[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:50])([CH3:49])[CH3:51])=[O:46])[CH2:41][CH2:40]5)=[C:24]([F:23])[CH:29]=4)=[CH:3][C:4]=3[N:8]=[CH:7]2)[CH2:11][CH2:10]1

null

13,912

339,331

Cl

null

ord_dataset-4706e7a7f3cd421bb42b7f877cff8af9

1996-01-01T00:09:00

true

5 ml of a 4N solution of hydrogen chloride in dioxane were added to a solution of 0.91 g of 1-t-butoxycarbonyl-2-(2-{2-[2-(4-ethylphenyl)ethyl]phenoxy}ethyl)piperidine [prepared as described in step (a) above] in 5 ml of dioxane, and the resulting solution was allowed to stand at room temperature for 1 hour. At the end of this time, the mixture was concentrated by distillation under reduced pressure, and the resulting oily residue was dissolved in a small amount of ethyl acetate. Diethyl ether was added to the solution, which was then allowed to stand at room temperature. The crystals which precipitated were collected by filtration and dried in vacuo, to give 687 mg (yield 88%) of the title compound as colorless crystals, melting at 74°-76° C.

CCc1ccc(CCc2ccccc2OCCC2CCCCN2)cc1

null

CCc1ccc(CCc2ccccc2OCCC2CCCCN2C(=O)OC(C)(C)C)cc1

null

[ClH:1].C(OC([N:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH3:33])=[CH:28][CH:27]=1)=O)(C)(C)C>O1CCOCC1>[ClH:1].[CH2:32]([C:29]1[CH:28]=[CH:27][C:26]([CH2:25][CH2:24][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[O:17][CH2:16][CH2:15][CH:10]2[CH2:11][CH2:12][CH2:13][CH2:14][NH:9]2)=[CH:31][CH:30]=1)[CH3:33]

1

C1COCCO1

null

88

null

697,727

1,710,360

Cl

null

ord_dataset-3f2a531ffbae4b9eb1048afcd7953beb

2016-01-01T00:04:00

true

A mixture of tert-butyl 3-hydroxy-1-oxa-7-azaspiro[4.4]nonane-7-carboxylate (CAN 1331825-50-3, 33 mg, 136 μmol) and a 4 M solution of HCl in dioxane (339 μL, 1.36 mmol) in dioxane (0.3 mL) was stirred at ambient temperature for 3 h to give the title compound (14 mg, 58%) as light brown oil which was sufficiently pure to be used in the next step; MS (EI): m/e=144.2 [(M-Cl)H+].

OC1COC2(CCNC2)C1

null

CC(C)(C)OC(=O)N1CCC2(CC(O)CO2)C1

null

[OH:1][CH:2]1[CH2:6][C:5]2([CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7]2)[O:4][CH2:3]1.[ClH:18]>O1CCOCC1>[ClH:18].[O:4]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7]2)[CH2:6][CH:2]([OH:1])[CH2:3]1

null

C1COCCO1

null

58

null

894,900

844,174

null

ord_dataset-e2b35e721c2741999b0005d12691f9fe

2008-01-01T00:10:00

true

The title compound is prepared from 2-chloro-N-(4-methoxy-phenyl)-acetamide [J. Heterocycl. Chem., 32, 1429. (1995)] and 4-benzyl-piperidine according to the method described in Example 143b. Melting Point: 81-83° C. (hexane)

COc1ccc(NC(=O)CN2CCC(Cc3ccccc3)CC2)cc1

null

c1ccc(CC2CCNCC2)cc1

COc1ccc(NC(=O)CCl)cc1

null

Cl[CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=1)=[O:4].[CH2:14]([CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CCCCCC>[CH2:14]([CH:21]1[CH2:26][CH2:25][N:24]([CH2:2][C:3]([NH:5][C:6]2[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=2)=[O:4])[CH2:23][CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

null

CCCCCC

null

140,505

1,666,444

[Au]

CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C

null

ord_dataset-9cc455db05a444779921f786a45b21a6

2015-01-01T00:12:00

true

A gold (Ag(I)) catalyst {[Au(JohnPhos)NCCH3]|SbF6—} [JohnPhos:(2-biphenyl)di-tert-butylphosphine] (11.3 mg, 0.015 mmol) was put into a reaction container, and dichloroethane (0.4 mL) was put thereinto. After stirring at room temperature for 5 minutes, ethyl hydrogen hex-1-ynylphosphonate (57.0 mg, 0.3 mmol) diluted with 0.5 mL of dichloroethane was added thereto, and finally, ethynylcyclohexane (64.9 mg, 0.6 mmol) was put thereinto. Then, when all of the starting materials disappeared in the TLC, the reaction was allowed to be completed. After the solvent was removed under low atmospheric pressure, the product was separated by chromatography to obtain 2-ethoxy-4-n-butyl-6-cyclohexyl-1,2-oxaphosphorin 2-oxide (42.1 mg, 47%) which is a title compound.

CCCCC1=CP(=O)(OCC)OC(C2CCCCC2)=C1

null

C#CC1CCCCC1

CCCCC#CP(=O)(O)OCC

null

CC(P(C(C)(C)C)C1C(C2C=CC=CC=2)=CC=CC=1)(C)C.[C:22]([P:28](=[O:33])([OH:32])[O:29][CH2:30][CH3:31])#[C:23][CH2:24][CH2:25][CH2:26][CH3:27].[C:34]([CH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1)#[CH:35]>[Au].ClC(Cl)C>[CH2:30]([O:29][P:28]1(=[O:32])[CH:22]=[C:23]([CH2:24][CH2:25][CH2:26][CH3:27])[CH:35]=[C:34]([CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)[O:33]1)[CH3:31]

0.08

CC(Cl)Cl

null

25

null

47

291,225

439,576

null

ord_dataset-3e8f24b5bc8e4d8bb9b6e7e89a956e12

1999-01-01T00:09:00

true

A solution of 7.5 g of (4-hydroxy-phenoxy)-acetonitrile dissolved in 60 ml of nitromethane was cooled in an ice bath and 3.88 ml of 70% nitric acid was added dropwise. After 45 minutes, the reaction mixture was poured into ethyl acetate, washed with brine, dried (MgSO4), and evaporated to dryness. The crude product was purified by silica gel chromatography eluting with ethyl acetate/hexane (1:3), giving 5.45 g of (4-hydroxy-3-nitro-phenoxy)-acetonitrile as a yellow solid, mp 113.1-114.1° C.

N#CCOc1ccc(O)c([N+](=O)[O-])c1

null

N#CCOc1ccc(O)cc1

O=[N+]([O-])O

null

[OH:1][C:2]1[CH:11]=[CH:10][C:5]([O:6][CH2:7][C:8]#[N:9])=[CH:4][CH:3]=1.[N+:12]([O-])([OH:14])=[O:13].C(OCC)(=O)C>[N+](C)([O-])=O>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][C:8]#[N:9])=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13]

0.75

CCOC(C)=O

C[N+](=O)[O-]

null

695,863

945,863

[Na+]

null

ord_dataset-ed680843f6d14f5c9901869b2a06b4a4

2010-01-01T00:03:00

true

A solution of biphenyl-2-ylcarbamic acid 1-(2-{[3-(2-aminoethylcarbamoyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester (9.31 g, 17.1 mmol; prepared as described in Preparation 8) and 4-hydroxybenzaldehyde10,411,879 (2.30 g, 18.8 mmol, 1.1 eq) in 125 mL MeOH was stirred at room temperature for 2 hours. Na(OAc)3BH (7.26 g, 34.2 mmol, 2.0 eq) was added to the reaction at room temperature in two portions separated in one hour interval. The reaction was stirred for an additional hour before being concentrated under vacuum. The residue was taken up in 100 mL DCM and stirred with 100 mL of 1.0 N HCl for 1 hour. The aqueous phase was adjusted to pH 9 using 10.0 N NaOH. The mixture was stirred for an additional 10 minutes. The organic phase was separated, dried over Na2SO4, filtered and concentrated under vacuum. The crude material was purified using silica gel chromatography (7% MeOH in CH2Cl2 with 1% NH4OH as eluent). The title compound was obtained as an off-white solid (8.08 g, 73%). MS m/z: [M+H+] calcd for C38H43N5O5, 650.34. Found, 650.2.

O=C(Nc1ccccc1-c1ccccc1)OC1CCN(CCNCC(=O)c2cccc(C(=O)NCCNCc3ccc(O)cc3)c2)CC1

null

NCCNC(=O)c1cccc(C(=O)CNCCN2CCC(OC(=O)Nc3ccccc3-c3ccccc3)CC2)c1

CC(=O)O[BH-](OC(C)=O)OC(C)=O

null

[NH2:1][CH2:2][CH2:3][NH:4][C:5]([C:7]1[CH:8]=[C:9]([CH:38]=[CH:39][CH:40]=1)[C:10]([CH2:12][NH:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][CH:19]([O:22][C:23](=[O:37])[NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:18][CH2:17]1)=[O:11])=[O:6].[BH-](O[C:51]([CH3:53])=[O:52])(OC(C)=O)OC(C)=O.[Na+]>CO>[OH:52][C:51]1[CH:53]=[CH:5][C:7]([CH2:8][NH:1][CH2:2][CH2:3][NH:4][C:5]([C:7]2[CH:8]=[C:9]([CH:38]=[CH:39][CH:40]=2)[C:10]([CH2:12][NH:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][CH:19]([O:22][C:23](=[O:37])[NH:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:18][CH2:17]2)=[O:11])=[O:6])=[CH:40][CH:39]=1

null

CO

null

636,695

1,353,608

null

ord_dataset-6034127657614f02860ed057b62b882e

2013-01-01T00:10:00

true

A 50 mL round bottom flask was charged with 8-methoxy-5-(thiophen-2-yl)-[1,2,4]triazolo[4,3-a]pyrazine (0.30 g, 1.3 mmol) and POCl3 (3 mL). The mixture was heated at 130° C. overnight. TLC indicated a complete conversion. Work-up: the reaction mixture was concentrated in vacuo. The residue was carefully poured into ice and extracted with EtOAc (10 mL). The organic layer was washed with saturated aqueous NaHCO3 and brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was further purified by flash column chromatography on silica gel with a 1:5 EtOAc/petroleum ether, to afford 0.23 g (75%) of the product as a white solid. MS m/z: 237 (M+H+).

Clc1ncc(-c2cccs2)n2cnnc12

null

O=P(Cl)(Cl)Cl

COc1ncc(-c2cccs2)n2cnnc12

null

CO[C:3]1[C:4]2[N:5]([CH:14]=[N:15][N:16]=2)[C:6]([C:9]2[S:10][CH:11]=[CH:12][CH:13]=2)=[CH:7][N:8]=1.O=P(Cl)(Cl)[Cl:19]>>[Cl:19][C:3]1[C:4]2[N:5]([CH:14]=[N:15][N:16]=2)[C:6]([C:9]2[S:10][CH:11]=[CH:12][CH:13]=2)=[CH:7][N:8]=1

null

130

null

75

551,929

676,796

O=C([O-])O

[Na+]

null

ord_dataset-50cdc205280641d2a3e264f32908e3d0

2005-01-01T00:07:00

true

To a solution of 1 g (20S)-4,4,20-trimethyl-pregna-8,14-dien-3β,21-diol in 10 ml dichloromethane 5.4 ml of a 0.5 M Dess-Martin-Periodinane solution were added at room temperature. The mixture was stirred for one hour, poured into saturated sodium bicarbonate solution, extracted with ethyl acetate and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to give 230 mg (20S)-3β-hydroxy-4,4,20-trimethyl-pregna-8,14-dien-21-al as a white solid.

C[C@H](C=O)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](O)C(C)(C)C1CC3

null

C[C@H](CO)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](O)C(C)(C)C1CC3

null

[CH3:1][C:2]1([CH3:26])[C@@H:22]([OH:23])[CH2:21][CH2:20][C@@:19]2([CH3:24])[CH:3]1[CH2:4][CH2:5][C:6]1[C:7]3[C@:15]([CH3:25])([CH2:16][CH2:17][C:18]=12)[C@@H:10]([C@H:11]([CH3:14])[CH2:12][OH:13])[CH2:9][CH:8]=3.C(=O)(O)[O-].[Na+]>ClCCl>[OH:23][C@H:22]1[CH2:21][CH2:20][C@@:19]2([CH3:24])[CH:3]([CH2:4][CH2:5][C:6]3[C:7]4[C@:15]([CH3:25])([CH2:16][CH2:17][C:18]=32)[C@@H:10]([C@H:11]([CH3:14])[CH:12]=[O:13])[CH2:9][CH:8]=4)[C:2]1([CH3:1])[CH3:26]

1

ClCCl

null

23.1

76,590

210,892

null

ord_dataset-e0a818f9350b46cdb184d2ac404ede9f

1990-01-01T00:06:00

true

A mixture of 3-amino-4-(4'-cyanophenyl)aminopyridine (9.31 g, 44.3 mmol), triethyl-orthoacetate (40 ml) and acetic anhydride (30 ml) was heated at reflux for 2 hours under nitrogen, cooled, then concentrated under reduced pressure. The brown residue was dissolved in 1M hydrochloric acid and washed with ethyl acetate (200 ml). The aqueous layer was rendered basic with saturated aqueous ammonia and extracted with dichloromethane (3×200 ml). The combined extracts were washed with water, dried (MgSO4) and concentrated to give 1-(4-cyanophenyl)-2-methylimidazo[4,5-c]pyridine, 6.5 g, as a brown solid.

Cc1nc2cnccc2n1-c1ccc(C#N)cc1

null

N#Cc1ccc(Nc2ccncc2N)cc1

CCC(CC)(CC)C([O-])([O-])[O-]

null

[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][CH:10]=1.[CH2:17](C(CC)(CC)C([O-])([O-])[O-])[CH3:18]>C(OC(=O)C)(=O)C>[C:15]([C:12]1[CH:13]=[CH:14][C:9]([N:8]2[C:7]3[CH:6]=[CH:5][N:4]=[CH:3][C:2]=3[N:1]=[C:17]2[CH3:18])=[CH:10][CH:11]=1)#[N:16]

null

CC(=O)OC(C)=O

null

307,925

1,576,362

O=C([O-])[O-]

[Cs+]

null

ord_dataset-9741bb5fd93044078df2a45f45733054

2015-01-01T00:04:00

true

To the crude material from Step 1 was added DMF (1.5 ml) followed by cesium carbonate (175 mg, 0.538 mmol) and bromoacetonitrile (24.99 μl, 0.359 mmol). The resulting mixture was stirred at 60° C. overnight affording clean conversion to desired product according to LC-MS. The mixture was filtered through Celite with the aid of DCM and the filtrate dried under reduced pressure. m/z (ESI) 577.1 (M+H)+.

COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(-c4ccc(Cl)cc4OCC#N)nccc3c2)cc1

null

COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(-c4ccc(Cl)cc4O)nccc3c2)cc1

N#CCBr

null

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([N:21]([CH2:27][C:28]4[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=4)[C:22]4[S:23][CH:24]=[CH:25][N:26]=4)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)=[C:4]([OH:36])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:44][C:45]#[N:46]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([N:21]([CH2:27][C:28]4[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=4)[C:22]4[S:23][CH:24]=[CH:25][N:26]=4)(=[O:19])=[O:20])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)=[C:4]([O:36][CH2:44][C:45]#[N:46])[CH:3]=1

8

CN(C)C=O

null

60

null

733,951

1,501,396

null

ord_dataset-366bdd9ee72d474cbe6f3f9e54dd96d2

2014-01-01T00:10:00

true

To a solution of methyl 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-ethylbenzoate (compound 215.5, 2.15 g, 4.99 mmol, 1.00 equiv) in methanol (20 mL), was added hydrazine hydrate (80%, 15 mL) batchwise. The reaction was stirred at 80° C. overnight. After cooling to ambient temperature, the mixture was concentrated under reduced pressure. The residue was extracted with dichloromethane (2×100 mL). The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography with dichloromethane/methanol (100:1) to furnish 1.13 g (53%) of the desired product as a pinkish solid.

CCc1cc(C2CCC2)c(C(=O)NN)cc1C(=O)N1CCC(c2ccc(C#N)cc2)CC1

null

NN

CCc1cc(C2CCC2)c(C(=O)OC)cc1C(=O)N1CCC(c2ccc(C#N)cc2)CC1

null

[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:18]([CH2:31][CH3:32])=[CH:19][C:20]([CH:27]4[CH2:30][CH2:29][CH2:28]4)=[C:21]([CH:26]=3)[C:22]([O:24]C)=O)=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2].O.[NH2:34][NH2:35]>CO>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:18]([CH2:31][CH3:32])=[CH:19][C:20]([CH:27]4[CH2:30][CH2:29][CH2:28]4)=[C:21]([CH:26]=3)[C:22]([NH:34][NH2:35])=[O:24])=[O:16])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2]

8

O

CO

null

80

null

53

201,383

406,263

null

ord_dataset-55e306db9b6b4befbc22504c12b7113d

1998-01-01T00:06:00

true

A solution of 1.17 g of the compound obtained in EXAMPLE 222 in 7.5 ml of DCM is cooled to +4° C., 15 ml of TFA are added and the reaction mixture is stirred for 3 hours 15 minutes at +4° C. It is concentrated under vacuum, the residue is taken up with DCM and the solvent is evaporated off under vacuum, this operation being repeated twice. The residue is taken up with AcOEt, the organic phase is washed with water and with a saturated solution of NaCl and dried over sodium sulfate and the solvent is evaporated off under vacuum to give 0.6 g of the expected product after trituration in iso ether and then crystallization from a DCM/iso ether mixture. M.p.=133° C.

CCN(CC)C(=O)N1CCc2cc(S(=O)(=O)N3C(=O)C(NCCC4CCNCC4)(c4ccccc4Cl)c4cc(Cl)ccc43)ccc21

O

CCC(C)(CC)NC(=O)N1CCc2cc(S(=O)(=O)N3C(=O)C(NCCC4CCN(C(=O)OC(C)(C)C)CC4)(c4ccccc4Cl)c4cc(Cl)ccc43)ccc21

null

C([O:5]C([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][NH:16][C:17]2([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=3[Cl:55])[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[N:19]([S:27]([C:30]3[CH:31]=[C:32]4[C:36](=[CH:37][CH:38]=3)[N:35]([C:39]([NH:41][C:42]([CH2:46]C)(CC)C)=[O:40])[CH2:34][CH2:33]4)(=[O:29])=[O:28])[C:18]2=[O:48])[CH2:10][CH2:9]1)=O)(C)(C)C.[C:56]([OH:62])([C:58]([F:61])([F:60])[F:59])=[O:57]>C(Cl)Cl>[OH2:5].[F:59][C:58]([F:61])([F:60])[C:56]([OH:62])=[O:57].[Cl:26][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][CH:22]=1)[N:19]([S:27]([C:30]1[CH:31]=[C:32]3[C:36](=[CH:37][CH:38]=1)[N:35]([C:39]([N:41]([CH2:42][CH3:46])[CH2:56][CH3:58])=[O:40])[CH2:34][CH2:33]3)(=[O:28])=[O:29])[C:18](=[O:48])[C:17]2([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=1[Cl:55])[NH:16][CH2:15][CH2:14][CH:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1

0.25

O=C(O)C(F)(F)F

ClCCl

null

364,774

1,260,598

COc1ccc2c(O)cc(-c3nc(C(C)C)cs3)nc2c1

null

ord_dataset-266f60b4555945d6afb2d2bdf5fa04e0

2013-01-01T00:02:00

true

Compound 269a was synthesized from compound 268a (3.50 g, 1 eq) as an orange solid in 84% yield, following the procedure as described for compound 218a (80° C. overnight). 1H NMR (CDCl3, 400 MHz): δ (ppm) 1.04-1.07 (m, 4H), 2.13-2.18 (m, 1H), 4.06 (s, 3H), 6.75 (s, 1H), 7.06 (d, J=9.10 Hz, 1H), 7.09 (s, 1H), 8.27 (d, J=9.10 Hz, 1H), 9.92 (br s, 1H); MS (ESI, EI+): m/z=333.13 (MH+).

COc1ccc2c(O)cc(-c3nc(C4CC4)cs3)nc2c1Cl

null

COc1ccc(C(C)=O)c(NC(=O)c2nc(C3CC3)cs2)c1Cl

null

[C:1]([C:4]1[C:9]([NH:10][C:11]([C:13]2[S:14][CH:15]=[C:16]([CH:18]3[CH2:20][CH2:19]3)[N:17]=2)=O)=[C:8]([Cl:21])[C:7]([O:22][CH3:23])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].C(C1N=C(C2C=C(O)C3C(=CC(OC)=CC=3)N=2)SC=1)(C)C>>[Cl:21][C:8]1[C:7]([O:22][CH3:23])=[CH:6][CH:5]=[C:4]2[C:9]=1[N:10]=[C:11]([C:13]1[S:14][CH:15]=[C:16]([CH:18]3[CH2:20][CH2:19]3)[N:17]=1)[CH:2]=[C:1]2[OH:3]

null

84

315,188

464,334

[Li]CCCC

null

ord_dataset-6c36eb0f817d4144988b8963c5d58879

2000-01-01T00:05:00

true

To a solution of 2.4 mL (18.49 mmol, 1.5 eq) of isopropylamine in 50 mL of dry THF at -78° C. under argon is added 9.3 mL (14.8 mmol, 1.2 eq) of 1.6 M BuLi in hexanes solution. This is stirred at -78° C. for 1 hour at which time 1.8 mL (13.56 mmol, 1.1 eq) of methyl isovalerate is added dropwise. This mixture is stirred at -78° C. for 1.5 hours at which time 2 g (12.33 mmol) of 5-phenylpentanal in 10 mL of dry THF is added dropwise. This is stirred at -78° C. for 1 hour, then allowed to warm slowly to 0° C. over 3 hours. The reaction is quenched with saturated NH4Cl solution and then partitioned between ether and saturated NH4Cl solution. The organics are dried (Na2SO4) and concentrated in vacuo. The product is purified by flash silica gel chromatography to afford methyl 3-hydroxy-3-isopropyl-7-phenylheptanoate in the form of a yellow oil. (0.88 g, 26%): 1H-NMR (300 MHz, CDCl3) δ (TMS) 0.95(t, 6H), 1.45(m, 3H), 1.6(m, 3H), 2.08(bs, 1H), 2.15(m, 1H), 2.35(t, 1H), 2.6(t, 2H), 3.68(s, 3H), 3.85(bm, 1H), 7.15(m, 3H), 7.25(m, 2H).

COC(=O)CC(O)(CCCCc1ccccc1)C(C)C

null

COC(=O)CC(C)C

O=CCCCCc1ccccc1

CC(C)N

[CH:1](N)([CH3:3])[CH3:2].[Li]CCCC.[C:10]([O:16][CH3:17])(=[O:15])[CH2:11]C(C)C.[C:18]1([CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[O:29])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1COCC1>[OH:29][C:28]([CH:1]([CH3:3])[CH3:2])([CH2:27][CH2:26][CH2:25][CH2:24][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:11][C:10]([O:16][CH3:17])=[O:15]

1

C1CCOC1

null

-78

null

391,019

188,591

null

ord_dataset-3ec273742a0345ea916ad5fd071167f2

1989-01-01T00:04:00

true

0.53 gram of daunorubicin in a free base is dissolved in 100 ml of methylene chloride. 1 ml of ethyl acetylacetate is added to the solution by constant stirring. The entire mixture is agitated for 12 hours at room temperature in a nitrogenic atmosphere. The reaction is checked by means of thin-layer chromatography on a silica gel in a toluene-acetone system in a ratio of 8:1. The solution is then evaporated until a small volume of composition remains and, the final product is pecipitated by the addition of a mixture of ethyl ether and hexane in a ratio of 1:1. The precipitated results from the mixture of acetone and ethyl ether. 0.4 g of N-(1-carboethoxy-propen-1-yl-2)-daunorubicin is obtained which corresponds to 60 percent of the theoretical yield. The composition decomposes at 151°-154° C., M.S.F.D. m/z 639 (M+, 80 percent of relative intensity); 640 (M+ +1, 100 percent of relative intensity); IR (KBr)ν=1590, 1610, 1650, 1670, 1715, 1720, cm-1 (chelate and free carbonyl groups).

CCOC(=O)/C=C(\C)N[C@H]1C[C@H](O[C@H]2C[C@](O)(C(C)=O)Cc3c(O)c4c(c(O)c32)C(=O)c2c(OC)cccc2C4=O)O[C@@H](C)[C@H]1O

null

COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(C)=O)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1

CCOC(=O)CC(C)=O

null

[CH3:1][C@@H:2]1[O:7][C@@H:6]([O:8][C@@H:9]2[C:14]3=[C:15]([OH:32])[C:16]4[C:28](=[O:29])[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][C:26]=5[O:30][CH3:31])[C:20](=[O:21])[C:17]=4[C:18]([OH:19])=[C:13]3[CH2:12][C@@:11]([OH:36])([C:33]([CH3:35])=[O:34])[CH2:10]2)[CH2:5][C@H:4]([NH2:37])[C@@H:3]1[OH:38].[C:39]([CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])(=O)[CH3:40].C1(C)C=CC=CC=1.CC(C)=O>C(Cl)Cl>[CH3:47][CH2:46][O:45][C:43](/[CH:42]=[C:39](/[NH:37][C@@H:4]1[C@H:3]([OH:38])[C@H:2]([CH3:1])[O:7][C@@H:6]([O:8][C@@H:9]2[C:14]3[C:13](=[C:18]([OH:19])[C:17]4[C:20](=[O:21])[C:22]5[CH:23]=[CH:24][CH:25]=[C:26]([O:30][CH3:31])[C:27]=5[C:28](=[O:29])[C:16]=4[C:15]=3[OH:32])[CH2:12][C@@:11]([OH:36])([C:33]([CH3:35])=[O:34])[CH2:10]2)[CH2:5]1)\[CH3:40])=[O:44]

12

Cc1ccccc1

ClCCl

CC(C)=O

25

null

547,502

846,200

O=C([O-])[O-]

[Cs+]

null

ord_dataset-e2b35e721c2741999b0005d12691f9fe

2008-01-01T00:10:00

true

A mixture of 6-bromopicolinic acid (2.02 g, 10 mmol), phenyboronic acid (1.22 g, 10 mmol), cesium carbonate (5.00 g) and PdCl2[(t-Bu)2P(OH)]2 (70 mg, CombiPhos Catalysts, Inc. Princeton, N.J.) in DMF (20 mL) and water (3 mL) was purged with Ar-gas and heated at 110° C. for 24 h. The reaction was incomplete and did not progress further. To the reaction mixture were added EtOAc (200 mL) and 1 N aq. HCl (40 mL). The EtOAc layer was separated, and the aqueous layer was washed with EtOAc (150 mL). The combined EtOAc layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC to afford the desired product (350 mg, 18%) as a white solid. 1H NMR (CDCl3) δ 10.45 (s, 1H), 8.18-7.96 (m, 5H), 7.51-7.53 (m, 3H).

O=C(O)c1cccc(-c2ccccc2)n1

null

O=C(O)c1cccc(Br)n1

OB(O)c1ccccc1

null

Br[C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][CH:3]=1.[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[C:11]1([C:2]2[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][CH:3]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

null

CN(C)C=O

O

null

110

17.6

null

412,512

97,457

null

ord_dataset-0bf72e95d80743729fdbb8b57a4bc0c6

1982-01-01T00:08:00

true

7β-[D-2-Amino-2-(4-hydroxyphenyl)acetamido]-7α-methoxy-3-(1-methyl-5-tetrazolyl)thiomethyl-3-cephem-4-carboxylic acid trifluoroacetic acid salt (150 mg) was subjected to suspension into ethyl acetate (7.5 ml) and was added thereto with stirring at 0° C. N,O-bis(trimethylsilyl) acetamide (417 μl). To the resulting mixture was added with stirring at 0° C. dihydroxychromon-3-carbonyl chloride (58 mg) which was obtained in the preceding Item (a). There was added once more N,O-bis(trimethylsilyl)acetamide (417 μl), and the whole was stirred at 0° C. for three hours. After addition of ethyl acetate (150 ml) to the reaction solution, the mixture was washed successively with 30 ml each of 0.5 N hydrochloric acid, distilled water (twice) and a saturated saline. The organic layer recovered therefrom was dried over magnesium sulfate, and the solvent was distilled off. The residue thus obtained was dissolved in acetone (30 ml) and allowed to stand at room temperature overnight. After removal by filtration of a small quantity of an insoluble matter separated out, the solvent was distilled off. Ethyl ether was added to the residue to cause trituration of the latter. There was thus obtained through filtration the desired substance (105 mg).

O=C(Cl)c1coc2cc(O)c(O)cc2c1=O

null

C/C(=N\[Si](C)(C)C)O[Si](C)(C)C

O=C(Cl)c1c(O)oc2cccc(O)c2c1=O

CCOC(C)=O

[CH3:1]/[C:2](/[O:8][Si](C)(C)C)=N\[Si](C)(C)C.O[C:14]1C=C[CH:21]=[C:20]2[C:15]=1[C:16](=[O:28])[C:17]([C:25]([Cl:27])=[O:26])=[C:18](O)[O:19]2.C(OCC)(=[O:31])C>>[OH:31][C:1]1[CH:14]=[C:15]2[C:20](=[CH:21][C:2]=1[OH:8])[O:19][CH:18]=[C:17]([C:25]([Cl:27])=[O:26])[C:16]2=[O:28]

null

0

null

154,444

1,581,377

null

ord_dataset-380e279f82154dba9e08ab51b3bdd08a

2015-01-01T00:05:00

true

Phenyl isoquinolin-1-ylcarbamate (80 mg, 0.30 mmol) and (2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methanamine (87 mg, 0.32 mmol) was dissolved in dimethyl sulfoxide. Then triethylamine (0.08 mL, 0.61 mmol) was added to it. The mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure. The crude was purified by column chromatography to give 1-(isoquinolin-1-yl)-3-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)urea (example compound 20) (46 mg, 34%).

CC1CCN(c2nc(C(F)(F)F)ccc2CNC(=O)Nc2nccc3ccccc23)CC1

null

O=C(Nc1nccc2ccccc12)Oc1ccccc1

CC1CCN(c2nc(C(F)(F)F)ccc2CN)CC1

null

[C:1]1([NH:11][C:12](=[O:20])OC2C=CC=CC=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.[CH3:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28]2[C:33]([CH2:34][NH2:35])=[CH:32][CH:31]=[C:30]([C:36]([F:39])([F:38])[F:37])[N:29]=2)[CH2:24][CH2:23]1.C(N(CC)CC)C>CS(C)=O.O>[C:1]1([NH:11][C:12]([NH:35][CH2:34][C:33]2[C:28]([N:25]3[CH2:26][CH2:27][CH:22]([CH3:21])[CH2:23][CH2:24]3)=[N:29][C:30]([C:36]([F:39])([F:37])[F:38])=[CH:31][CH:32]=2)=[O:20])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1

12

CS(C)=O

CCN(CC)CC

O

25

null

34.6

817,996

138,075

null

ord_dataset-3fa0a6b7d51b4fc6a5380aa0d03ac884

1985-01-01T00:12:00

true

One g of 1-[2-(1,4-benzodioxan-2-yl)-2-hydroxyethyl]-4-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine is dissolved in 15 ml of pyridine and cooled in an ice bath to 0°-5° C. Acetic anhydride (0.6 g) is slowly added and the reaction mixture is stirred for 2 hr. After the addition of 100 ml of water, the reaction mixture is extracted twice with 100-ml portions of diethylether. After combining, the ether portion is washed twice with 100 ml of water and evaporated to dryness to produce 1-[2-(1,4-benzodioxan-2-yl)-2-acetoxyethyl]-4-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine as an oil.

CC(=O)OC(CN1CCN(CC(=O)Nc2c(C)cccc2C)CC1)C1COc2ccccc2O1

null

Cc1cccc(C)c1NC(=O)CN1CCN(CC(O)C2COc3ccccc3O2)CC1

CC(=O)OC(C)=O

null

[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH:11]([OH:31])[CH2:12][N:13]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]([NH:22][C:23]2[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][C:24]=2[CH3:30])=[O:21])[CH2:15][CH2:14]1.[C:32](OC(=O)C)(=[O:34])[CH3:33].O>N1C=CC=CC=1>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH:11]([O:31][C:32](=[O:34])[CH3:33])[CH2:12][N:13]1[CH2:14][CH2:15][N:16]([CH2:19][C:20]([NH:22][C:23]2[C:24]([CH3:30])=[CH:25][CH:26]=[CH:27][C:28]=2[CH3:29])=[O:21])[CH2:17][CH2:18]1

2

c1ccncc1

O

null

29,387

549,182

CC(=O)[O-]

Cl

[Na+]

null

ord_dataset-e967d076b4894c2c854795f019ed3c39

2002-01-01T00:06:00

true

4-Dimethylamino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione was prepared by the procedure of Example 1 from 3-dimethylaminophthalic anhydride (1.34 g, 7.0 mmol), 3-aminopiperidine-2,6-dione hydrogen chloride (1.15 g, 7.0 mmol) and sodium acetate (0.60 g, 7.3 mmol) in acetic acid (20 mL). The product was a yellow solid (1.59 g, 75% yield); mp, 214.5-216.5° C.; 1H NMR (DMSO-d6) δ1.98-2.09 (m, 1H, CHH), 2.49-2.62 (m, 2H, CH2), 2.81-2.95 (m, 1H, CHH), 3.04 (s, 6H, CH3), 5.08 (dd, J=5.5, 12.7 Hz, 1H, NCH), 7.23 (d, J=6.6 Hz, 1H, Ar), 7.26 (d, J=8.1 Hz, 1H, Ar), 7.63 (dd, J=6.9, 8.6 Hz, 1H, Ar), 11.09 (br s, 1H, NH); 13C NMR (DMSO-d6) δ22.10, 30.96, 42.95, 48.77, 112.99, 113.41, 122.59, 133.90, 135.22, 149.88, 166.29, 167.13, 170.06, 172.83; Anal Calcd for C15H15N3O4: C, 59.80; H, 5.02; N, 13.95. Found: C, 59.60; H, 4.94; N, 13.80.

CN(C)c1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

null

NC1CCC(=O)NC1=O

CN(C)c1cccc2c1C(=O)OC2=O

null

[CH3:1][N:2]([CH3:14])[C:3]1[CH:13]=[CH:12][CH:11]=[C:5]2[C:6]([O:8][C:9](=[O:10])[C:4]=12)=O.Cl.[NH2:16][CH:17]1[CH2:22][CH2:21][C:20](=[O:23])[NH:19][C:18]1=[O:24].C([O-])(=O)C.[Na+]>C(O)(=O)C>[CH3:14][N:2]([CH3:1])[C:3]1[CH:13]=[CH:12][CH:11]=[C:5]2[C:4]=1[C:9](=[O:10])[N:16]([CH:17]1[CH2:22][CH2:21][C:20](=[O:23])[NH:19][C:18]1=[O:24])[C:6]2=[O:8]

null

CC(=O)O

null

38,134

1,143,744

null

ord_dataset-68715347640045adb1b09e6a04722b0e

2012-01-01T00:03:00

true

5-bromo-1-(2,2,2-trifluoroethyl)pyridin-2(1H)-one was prepared from 5-bromopyridin-2(1H)-one and 2,2,2-trifluoroethyl trifluoromethanesulfonate following a procedure analogous to that described in Example 59 Step 1.

O=c1ccc(Br)cn1CC(F)(F)F

null

O=c1ccc(Br)c[nH]1

O=S(=O)(OCC(F)(F)F)C(F)(F)F

null

[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.FC(F)(F)S(O[CH2:15][C:16]([F:19])([F:18])[F:17])(=O)=O>>[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[N:6]([CH2:15][C:16]([F:19])([F:18])[F:17])[CH:7]=1

null

90,373

427,050

O=C([O-])[O-]

[K+]

null

ord_dataset-8cce6f317d644b348a7978a2dce3ea01

1999-01-01T00:03:00

true

2.1 g of 7-(4,6-dimethoxypyrimidin-2-yl)-4-(2-furyl)-7-hydroxyfuro[3,4-b]pyridin-5(7H)one was weighed out, and 50 ml of N,N-dimethylformamide and 0.82 g of potassium carbonate were added thereto. The mixture was stirred at room temperature. 0.8 g of methyl iodide was added thereto dropwise, and the mixture was stirred at room temperature overnight, then poured into water and extracted 200 ml of ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (developing solvent: ethyl acetate/hexane=1/3) to obtain 1.1 g (yield 50.7%) of the desired compound as brown crystals. m.p.: 135°-140° C.

COC(=O)c1c(-c2ccco2)ccnc1C(=O)c1nc(OC)cc(OC)n1

null

CN(C)C=O

COc1cc(OC)nc(C2(O)OC(=O)c3c(-c4ccco4)ccnc32)n1

null

[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([C:11]2([OH:26])[C:15]3=[N:16][CH:17]=[CH:18][C:19]([C:20]4[O:21][CH:22]=[CH:23][CH:24]=4)=[C:14]3[C:13](=[O:25])[O:12]2)[N:4]=1.[CH3:27]N(C)C=O.C(=O)([O-])[O-].[K+].[K+].CI>O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([C:11]([C:15]2[N:16]=[CH:17][CH:18]=[C:19]([C:20]3[O:21][CH:22]=[CH:23][CH:24]=3)[C:14]=2[C:13]([O:12][CH3:27])=[O:25])=[O:26])[N:4]=1

null

O

CI

null

25

null

50.7

23,117

1,513,904

null

ord_dataset-8c74302143c04eb9983e4b3a7ead2d72

2014-01-01T00:12:00

true

Ammonia in methanol (7 N solution, 15 mL) was added dropwise to stirred neat 2,4-dichloro-5-(trifluoromethyl)pyrimidine 131 (5.0 g, 23.04 mmol) under argon, and the resulting mixture was stirred at RT for 2 h. The reaction mixture was quenched with water and then extracted with ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash chromatography on silica gel (0-20% ethyl acetate-hexanes) to afford the product 4-chloro-5-(trifluoromethyl)pyrimidin-2-amine 132. The regio-isomer 2-chloro-5-(trifluoromethyl)pyrimidin-4-amine 133 can also be isolated.

Nc1ncc(C(F)(F)F)c(Cl)n1

null

N

FC(F)(F)c1cnc(Cl)nc1Cl

null

[NH3:1].Cl[C:3]1[N:8]=[C:7]([Cl:9])[C:6]([C:10]([F:13])([F:12])[F:11])=[CH:5][N:4]=1>CO>[Cl:9][C:7]1[C:6]([C:10]([F:13])([F:12])[F:11])=[CH:5][N:4]=[C:3]([NH2:1])[N:8]=1

2

CO

null

25

null

719,689

717,503

O=C([O-])O

[Na+]

null

ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa

2006-01-01T00:07:00

true

Into 4.0 mL of chloroform was dissolved 200 mg of Compound 19, and 194 mg of benzyltrimethylammonium tribromide was added, followed by 1 hour of stirring at room temperature. The reaction was terminated by adding water to the reaction solution and then the solvent was once removed by evaporation. The residue was adjusted to pH 2 to 3 by adding 1 mol/L hydrochloric acid, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. The solvent was removed by evaporation under reduced pressure and the resulting residue was washed with methanol to obtain 201 mg of N-(4-bromoacetyl-2-methanesulfonylphenyl)-5-fluoro-3-methylbenzo[b]thiophene-2-sulfonamide as a colorless solid. The thus obtained N-(4-bromoacetyl-2-methanesulfonylphenyl)-5-fluoro-3-methylbenzo[b]thiophene-2-sulfonamide (150 mg) was dissolved into a mixed solution of 1.5 mL of dioxane and 1.5 mL of ethanol, and 53 mg of sodium hydrogen carbonate and 26 mg of thioacetamide were successively added, followed by 2 hours of stirring under heating and refluxing. The reaction was terminated by adding water to the reaction solution and then the solvent was removed by evaporation under reduced pressure. The residue was adjusted to pH 2 to 3 by adding 1 mol/L hydrochloric acid, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. The solvent was removed by evaporation under reduced pressure and the resulting residue was purified by silica gel column chromatography to obtain 61 mg of the title compound as light yellow powder.

Cc1nc(-c2ccc(NS(=O)(=O)c3sc4ccc(F)cc4c3C)c(S(C)(=O)=O)c2)cs1

null

CC(N)=S

Cc1c(S(=O)(=O)Nc2ccc(C(=O)CBr)cc2S(C)(=O)=O)sc2ccc(F)cc12

null

Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][S:12]([C:15]2[S:19][C:18]3[CH:20]=[CH:21][C:22]([F:24])=[CH:23][C:17]=3[C:16]=2[CH3:25])(=[O:14])=[O:13])=[C:7]([S:26]([CH3:29])(=[O:28])=[O:27])[CH:6]=1)=O.O1CCOCC1.C(=O)([O-])O.[Na+].[C:41]([NH2:44])(=[S:43])[CH3:42]>C(O)C>[F:24][C:22]1[CH:21]=[CH:20][C:18]2[S:19][C:15]([S:12]([NH:11][C:8]3[CH:9]=[CH:10][C:5]([C:3]4[N:44]=[C:41]([CH3:42])[S:43][CH:2]=4)=[CH:6][C:7]=3[S:26]([CH3:29])(=[O:28])=[O:27])(=[O:13])=[O:14])=[C:16]([CH3:25])[C:17]=2[CH:23]=1

2

CCO

C1COCCO1

null

42.6

null

133,151

921,749

null

ord_dataset-8e59bd24817446f7b1c68e805b8e5f1d

2009-01-01T00:11:00

true

To a chilled suspension of 3-aminobenzyl alcohol (9.24 g, 75 mmol) in THF (50 mL) was added neat acetic anhydride (8.1 mL, 86 mmol). The reaction mixture was stirred cold for 1 hr, diluted with EtOAc, washed with aq. NaOH and brine, and concentrated in vacuo to give N-[3-(hydroxymethyl)phenyl]acetamide (10.5 g, 85%).

CC(=O)Nc1cccc(CO)c1

null

Nc1cccc(CO)c1

CC(=O)OC(C)=O

null

[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].[C:10](OC(=O)C)(=[O:12])[CH3:11]>C1COCC1.CCOC(C)=O>[OH:6][CH2:5][C:4]1[CH:3]=[C:2]([NH:1][C:10](=[O:12])[CH3:11])[CH:9]=[CH:8][CH:7]=1

1

C1CCOC1

CCOC(C)=O

null

84.8

807,901

434,485

null

ord_dataset-386da077ab2340638cada986e2ef0770

1999-01-01T00:07:00

true

By the same procedure as described in the example 1, synthesis was carried out starting with 4-[1-[3-(ethylamino)-2-pyridyl]piperazin-4-yl-carbonyl]benzoic acid and using 2-(ethylamino)ethanol. Then, the product was recrystallized using ethyl acetate and hexane to give the desired compound.

CCNc1cccnc1N1CCN(C(=O)c2ccc(C(=O)N(CC)CCO)cc2)CC1

null

CCNCCO

CCNc1cccnc1N1CCN(C(=O)c2ccc(C(=O)O)cc2)CC1

null

[CH2:1]([NH:3][C:4]1[C:5]([N:10]2[CH2:15][CH2:14][N:13]([C:16]([C:18]3[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=3)=[O:17])[CH2:12][CH2:11]2)=[N:6][CH:7]=[CH:8][CH:9]=1)[CH3:2].[CH2:27]([NH:29][CH2:30][CH2:31][OH:32])[CH3:28]>>[CH2:27]([N:29]([CH2:30][CH2:31][OH:32])[C:22]([C:21]1[CH:20]=[CH:19][C:18]([C:16]([N:13]2[CH2:14][CH2:15][N:10]([C:5]3[C:4]([NH:3][CH2:1][CH3:2])=[CH:9][CH:8]=[CH:7][N:6]=3)[CH2:11][CH2:12]2)=[O:17])=[CH:26][CH:25]=1)=[O:24])[CH3:28]

null

72

null

278,261

824,240

[BH4-]

[Na+]

null

ord_dataset-0ca5627a13c049a99463095023b09fe5

2008-01-01T00:06:00

true

A solution of Example 227 (1.0 equiv) in MeOH (0.2 M solution) was treated with formaldehyde (5 equiv) and stirred at room temperature (r.t.) for 2 hours. Sodium Borohydride was added and stirred at r.t. overnight. The solvent was removed under vacuum and crude residue was purified by silica gel chromatography using the appropriate eluent (typically mixtures CHCl3/EtOH 7%/NH4OH 0.7%) to afford the title compound as a solid.

Cc1cc(CN(C)CCC(C)C)ccc1Oc1ccc(C(N)=O)cn1

null

C=O

Cc1cc(CNCCC(C)C)ccc1Oc1ccc(C(N)=O)cn1

null

[CH3:1][C:2]1[CH:17]=[C:16]([CH2:18][NH:19][CH2:20][CH2:21][CH:22]([CH3:24])[CH3:23])[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH2:11])=[O:10])=[CH:7][N:6]=1.[CH2:25]=O.[BH4-].[Na+]>CO>[CH3:1][C:2]1[CH:17]=[C:16]([CH2:18][N:19]([CH3:25])[CH2:20][CH2:21][CH:22]([CH3:24])[CH3:23])[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH2:11])=[O:10])=[CH:7][N:6]=1

2

CO

null

25

20

null

145,812

107,881

[Na+]

[OH-]

null

ord_dataset-29d79fca4cec4a43b773d0ba25b27651

1983-01-01T00:08:00

true

A solution of ethyl 2-(2-aminothiazol-4-yl)-2-allyloxyiminoacetate (syn isomer, 3.6 g.), 2 N aqueous solution of sodium hydroxide (14.1 ml.), tetrahydrofuran (14.1 ml.) and methanol (15 ml.) was stirred at 40° C. for 1.5 hours. The resultant solution was concentrated in vacuo, and the residue was dissolved in water. After the solution was adjusted to pH 2.8 with 10% hydrochloric acid under ice cooling, the precipitates were collected by filtration, washed with water and acetone in turn and dried to give 2-(2-aminothiazol-4-yl)-2-allyloxyiminoacetic acid (syn isomer, 1.91 g.), mp. 187° C. (dec.).

C=CCON=C(C(=O)O)c1csc(N)n1

null

C=CCON=C(C(=O)OCC)c1csc(N)n1

null

[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:13][O:14][CH2:15][CH:16]=[CH2:17])[C:8]([O:10]CC)=[O:9])[N:6]=1.[OH-].[Na+].O1CCCC1>CO>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:13][O:14][CH2:15][CH:16]=[CH2:17])[C:8]([OH:10])=[O:9])[N:6]=1

null

CO

C1CCOC1

null

59.6

162,516

1,278,911

null

ord_dataset-d5c54236ecd94d61aaa071461bcfc426

2013-01-01T00:04:00

true

Following a procedure analogous to the procedure described in Example 1 using 2-aminoethyl-methyl-sulfone (923 mg, 7.49 mmol) and N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1-pyrrolidinyl)-1,3-thiazol-4-yl]phenyl}-2,6-difluorobenzenesulfonamide (400 mg, 0.749 mmol) the title compound was obtained as a white solid (27 mg, 4% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.87-11.12 (m, 1H) 7.75 (d, J=5.4 Hz, 1H) 7.55-7.72 (m, 1H) 7.24-7.38 (m, 1H) 7.10-7.25 (m, 4H) 7.08 (d, J=7.8 Hz, 1H) 5.57-5.85 (m, 1H) 3.54-3.70 (m, 2H) 3.29-3.43 (m, 7H) 2.88-3.05 (m, 4H) 1.86-2.04 (m, 3H). MS (ESI): 621.1 [M+H]+.

CS(=O)(=O)CCNc1nccc(-c2sc(N3CCCC3)nc2-c2cccc(NS(=O)(=O)c3c(F)cccc3F)c2)n1

null

CS(=O)(=O)CCN

O=S(=O)(Nc1cccc(-c2nc(N3CCCC3)sc2-c2ccnc(Cl)n2)c1)c1c(F)cccc1F

null

[NH2:1][CH2:2][CH2:3][S:4]([CH3:7])(=[O:6])=[O:5].Cl[C:9]1[N:14]=[C:13]([C:15]2[S:19][C:18]([N:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)=[N:17][C:16]=2[C:25]2[CH:26]=[C:27]([NH:31][S:32]([C:35]3[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:36]=3[F:42])(=[O:34])=[O:33])[CH:28]=[CH:29][CH:30]=2)[CH:12]=[CH:11][N:10]=1>>[F:42][C:36]1[CH:37]=[CH:38][CH:39]=[C:40]([F:41])[C:35]=1[S:32]([NH:31][C:27]1[CH:28]=[CH:29][CH:30]=[C:25]([C:16]2[N:17]=[C:18]([N:20]3[CH2:21][CH2:22][CH2:23][CH2:24]3)[S:19][C:15]=2[C:13]2[CH:12]=[CH:11][N:10]=[C:9]([NH:1][CH2:2][CH2:3][S:4]([CH3:7])(=[O:6])=[O:5])[N:14]=2)[CH:26]=1)(=[O:34])=[O:33]

null

432,958

310,655

O=S(=O)([O-])O

[K+]

null

ord_dataset-081613ef79bd4110aacc146b4465f086

1995-01-01T00:05:00

true

A solution of 1.5 g (5. mmol) of 1-[2-(4-fluorophenyl) cyclopenten-1-yl]-4-(methylthio)benzene (Step 3) in 46 mL of methanol/thf (1:1) was slowly treated with 5.2 g (8.4 mmol) of Oxone® [2 KHSO5.KHSO4.K2SO4 ] in 23 mL of water. After stirring for 4 h, the solvent was removed in vacuo. The residue was dissolved in ethyl acetate and washed with water and brine, dried (MgSO4), and reconcentrated. Recrystallization from ethyl acetate/hexane provided 960 mg (54%) of 1-[2-(4-fluorophenyl)cyclopenten-1-yl]-4-(methylsulfonyl)benzene (41 in Synthetic Scheme X when R5 =SO2CH3, R10 =F, and R1, R2, R3, R4, R6, R7, R8, R9, R11, and R12 =H) as a colorless solid: mp 138°-139° C.; NMR (CDCl3) d 2.09 (m, J=7 Hz, 2H), 2.91 (t, J=7 Hz, 4H), 3.04 (s, 3H), 6.88-6.96 (m, 2H), 7.06-7.14 (m, 2H), 7.32 (d, J=8 Hz, 2H), 7.76 (d, J=8 Hz, 2H). MS (EI) m/e (rel intensity) 316 (100), 237 (41), 161 (13); HRMS. Calc'd for C18H17FO2S: 316.0933. Found: 316.0943. Anal. Calc'd for C18H17FO2S: C, 68.33; H, 5.42; F, 6.00; S, 10.13. Found: C, 68.08; H, 5.45; F, 6.42; S, 9.98.

CS(=O)(=O)c1ccc(C2=C(c3ccc(F)cc3)CCC2)cc1

null

O=S([O-])OO

CSc1ccc(C2=C(c3ccc(F)cc3)CCC2)cc1

CO

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][CH2:11][CH2:10][C:9]=2[C:13]2[CH:18]=[CH:17][C:16](SC)=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.O[O:22][S:23]([O-:25])=O.[K+].OS([O-])(=O)=O.[K+].[CH3:33]O>O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH2:12][CH2:11][CH2:10][C:9]=2[C:13]2[CH:14]=[CH:15][C:16]([S:23]([CH3:33])(=[O:25])=[O:22])=[CH:17][CH:18]=2)=[CH:6][CH:7]=1

4

O

null

54

746,562

1,038,375

null

ord_dataset-3af92aec23dc4810b92eb0d8c60023ee

2011-01-01T00:03:00

true

The title compound was synthesized in two steps. First, methyl 4-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate was reacted with (4-fluoro-2-methylbenzyl)magnesium bromide) according to General Procedure 3. The resulting product was then converted to the title compound by hydrogenation according to General Procedure 6.

COC(=O)c1cc2c([nH]1)CCC2Cc1ccc(F)cc1C

null

COC(=O)c1cc2c([nH]1)CCC2=O

Cc1cc(F)ccc1C[Mg]Br

null

O=[C:2]1[C:9]2[CH:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[NH:6][C:5]=2[CH2:4][CH2:3]1.[F:14][C:15]1[CH:23]=[CH:22][C:18]([CH2:19][Mg]Br)=[C:17]([CH3:24])[CH:16]=1>>[F:14][C:15]1[CH:23]=[CH:22][C:18]([CH2:19][CH:2]2[C:9]3[CH:8]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[NH:6][C:5]=3[CH2:4][CH2:3]2)=[C:17]([CH3:24])[CH:16]=1

null

91,633

1,183,466

CC(C)(C)[O-]

O=C(O)CC(O)(CC(=O)O)C(=O)O

[K+]

null

ord_dataset-9cd817a75dfc4fe7ad19d4232772d5ff

2012-01-01T00:07:00

true

N-BOC-4-hydroxy-L-proline (A; 281 mg; 1.21 mmol) was dissolved in dimethylsulfoxide (3 mL) at room temperature then potassium t-butoxide (270 mg; 2.4 mmol) was added. The resulting solution was stirred at room temperature for 2 hours, then cooled to 0° C. A solution of 1-chloro-6-methoxy-3-methylisoquinoline in dimethylsulfoxide (3 mL) was then added dropwise to the cold solution, followed by t-BuOK, and the mixture was allowed to warn to room temperature. The solution was stirred for 16 hours. The reaction mixture was acidified to pH=4 with 5% aq. citric acid. The solution was extracted with ethyl acetate and the organic phase washed with water followed by brine. The organic phase was concentrated under reduced pressure to give (2S,4R)-1-(tert-butoxycarbonyl)-4-(6-methoxy-3-methylisoquinolin-1-yloxy)pyrrolidine-2-carboxylic acid.

COc1ccc2c(O[C@@H]3C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)C3)nc(C)cc2c1

null

CC(C)(C)OC(=O)N1CC(O)C[C@H]1C(=O)O

COc1ccc2c(Cl)nc(C)cc2c1

null

[C:1]([N:8]1[CH2:15][CH:14]([OH:16])[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC(C)([O-])C.[K+].Cl[C:24]1[C:33]2[C:28](=[CH:29][C:30]([O:34][CH3:35])=[CH:31][CH:32]=2)[CH:27]=[C:26]([CH3:36])[N:25]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O>[C:4]([O:3][C:1]([N:8]1[CH2:15][C@H:14]([O:16][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:34][CH3:35])=[CH:31][CH:32]=3)[CH:27]=[C:26]([CH3:36])[N:25]=2)[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])=[O:2])([CH3:7])([CH3:6])[CH3:5]

2

CS(C)=O

null

25

null

512,201

637,984

c1ccc(P(c2ccccc2)c2ccccc2)cc1

null

ord_dataset-a192df1b44174b5886ef2005f759d553

2004-01-01T00:05:00

true

44 g (167 mmol) of triphenylphosphine were added to a solution of 24 g (152 mmol) of 5-hydroxymethyl-3-methylthiophene-2-carbonitrile in 180 ml of tetrahydrofuran. Then, a solution of 55 g (167 mmol) of tetrabromomethane in 100 ml of tetrahydrofuran was added. The mixture was stirred for 90 minutes at room temperature. The reaction mixture was concentrated on a rotary evaporator under a water pump vacuum, and the residue was purified by column chromatography (eluant hexane:ethyl acetate 8:2). This gave 34 g of the title compound which still contained a small amount of solvent. 1H NMR (270 MHz, DMSO-d6): δ=2.4 (s, 3H), 5.0 (s, 2H), 7.3 (s, 1H).

Cc1cc(CBr)sc1C#N

null

Cc1cc(CO)sc1C#N

BrC(Br)(Br)Br

null

C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:21][C:22]1[S:26][C:25]([C:27]#[N:28])=[C:24]([CH3:29])[CH:23]=1.[Br:30]C(Br)(Br)Br>O1CCCC1>[Br:30][CH2:21][C:22]1[S:26][C:25]([C:27]#[N:28])=[C:24]([CH3:29])[CH:23]=1

1.5

C1CCOC1

null

25

null

353,778

19,200

[Cu]

null

ord_dataset-8ca24382d55b4303bc34393399f4110e

1977-01-01T00:01:00

true

4-Iodophenyl acetate (7.86 g, 0.030 mole), 1,17-diiodoperfluoro-3,6,9,15-tetraoxaheptadecane (9.68 g, 0.010 mole), and copper bronze (5.08 g, 0.080 g atom) were stirred together under nitrogen at 113°-117° C for 48 hours. The cooled reaction mixture was added to 200 ml of ether. The cuprous salts and excess copper were filtered off and washed on the frit with ether. The ethereal solution was washed several times with water to remove the reaction solvent, dried over anhydrous magnesium sulfate, and reduced in volume under reduced pressure to yield a brown oil. The oil was refluxed with 10 ml of acetic anhydride for 20 minutes and the excess acetic anhydride then distilled off under reduced pressure. Distillation of the residue yielded 4.53 g of 1,17-bis (4-acetoxyphenyl)perfluoro-3,6,9,15-tetraoxaheptadecane, b.p. 184°-189° C/0.10 mm.

CC(=O)Oc1ccc(C(F)(F)C(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)OC(F)(F)C(F)(F)c2ccc(OC(C)=O)cc2)cc1

null

CC(=O)Oc1ccc(I)cc1

FC(F)(I)C(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)OC(F)(F)C(F)(F)I

CC(=O)OC(C)=O

[C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].I[C:13]([F:56])([F:55])[C:14]([F:54])([F:53])[O:15][C:16]([F:52])([F:51])[C:17]([F:50])([F:49])[O:18][C:19]([F:48])([F:47])[C:20]([F:46])([F:45])[O:21][C:22]([F:44])([F:43])[C:23]([F:42])([F:41])[C:24]([F:40])([F:39])[C:25]([F:38])([F:37])[C:26]([F:36])([F:35])[O:27][C:28]([F:34])([F:33])[C:29]([F:32])([F:31])I.[C:57]([O:60][C:61](=O)[CH3:62])(=[O:59])[CH3:58]>[Cu].CCOCC>[C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:13]([F:56])([F:55])[C:14]([F:54])([F:53])[O:15][C:16]([F:52])([F:51])[C:17]([F:50])([F:49])[O:18][C:19]([F:48])([F:47])[C:20]([F:46])([F:45])[O:21][C:22]([F:44])([F:43])[C:23]([F:42])([F:41])[C:24]([F:40])([F:39])[C:25]([F:38])([F:37])[C:26]([F:36])([F:35])[O:27][C:28]([F:34])([F:33])[C:29]([F:32])([F:31])[C:5]2[CH:10]=[CH:62][C:61]([O:60][C:57](=[O:59])[CH3:58])=[CH:7][CH:6]=2)=[CH:7][CH:6]=1)(=[O:3])[CH3:2]

null

CCOCC

null

902,464

1,154,343

Cl

O=C(n1ccnc1)n1ccnc1

null

ord_dataset-b195433d5c354ddfb6cde0d53c41910f

2012-01-01T00:04:00

true

Treat a solution of 3′-chloro-4′-[2-oxo-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-3-ylmethyl]-biphenyl-4-carboxylic acid (0.2 g, 0.34 mmol) in CH2Cl2 (15 mL) with 1,1′-carbonyldiimidazole (0.11 g, 0.68 mmol) and stir for 1 hour at room temperature. Treat the reaction with 4,4-difluoropiperidine hydrochloride (0.08 g, 0.51 mmol) and diisopropylethylamine (0.07 g, 0.51 mmol) and stir for 12 hours at room temperature. Load the mixture on silica gel column, flash with 0% to 50% ethyl acetate in hexanes to afford 0.15 g (64%) of the title compound. MS (m/z): 688 (M+).

CC(C)[Si](OC1CCN(N2CC[C@@H](Cc3ccc(-c4ccc(C(=O)N5CCC(F)(F)CC5)cc4)cc3Cl)C2=O)CC1)(C(C)C)C(C)C

null

FC1(F)CCNCC1

CC(C)[Si](OC1CCN(N2CCC(Cc3ccc(-c4ccc(C(=O)O)cc4)cc3Cl)C2=O)CC1)(C(C)C)C(C)C

null

[Cl:1][C:2]1[CH:3]=[C:4]([C:32]2[CH:37]=[CH:36][C:35]([C:38](O)=[O:39])=[CH:34][CH:33]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][CH:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][CH:17]([O:20][Si:21]([CH:28]([CH3:30])[CH3:29])([CH:25]([CH3:27])[CH3:26])[CH:22]([CH3:24])[CH3:23])[CH2:16][CH2:15]2)[C:10]1=[O:31].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[F:54][C:55]1([F:61])[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:32]2[CH:37]=[CH:36][C:35]([C:38]([N:58]3[CH2:59][CH2:60][C:55]([F:61])([F:54])[CH2:56][CH2:57]3)=[O:39])=[CH:34][CH:33]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:15][CH2:16][CH:17]([O:20][Si:21]([CH:25]([CH3:27])[CH3:26])([CH:28]([CH3:29])[CH3:30])[CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:19]2)[C:10]1=[O:31]

1

ClCCl

CCN(C(C)C)C(C)C

CCOC(C)=O

25

64.1

null

916,829

820,137

Cl

null

ord_dataset-ec58fad8331a42c5a67ad75aac6713b4

2008-01-01T00:05:00

true

To a solution of 2-ethyl-4-{(E)-2-[3-(methoxymethoxy)-1-phenyl-1H-pyrazol-4-yl]ethenyl}-1,3-oxazole (2.57 g) in methanol (30 mL) was added concentrated hydrochloric acid (1.33 mL) at room temperature, and the mixture was stirred at 50° C. for 1 hr. The reaction mixture was evaporated under reduced pressure, and the residue was washed with diethyl ether to give 4-[(E)-2-(2-ethyl-1,3-oxazol-4-yl)ethenyl]-1-phenyl-1H-pyrazol-3-ol.hydrochloride (2.00 g, yield 90%) as orange crystals. melting point: 157-159° C.

CCc1nc(/C=C/c2cn(-c3ccccc3)nc2O)co1

null

CCc1nc(/C=C/c2cn(-c3ccccc3)nc2OCOC)co1

null

[CH2:1]([C:3]1[O:4][CH:5]=[C:6](/[CH:8]=[CH:9]/[C:10]2[C:11]([O:21]COC)=[N:12][N:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:14]=2)[N:7]=1)[CH3:2].[ClH:25]>CO>[ClH:25].[CH2:1]([C:3]1[O:4][CH:5]=[C:6](/[CH:8]=[CH:9]/[C:10]2[C:11]([OH:21])=[N:12][N:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:14]=2)[N:7]=1)[CH3:2]

1

CO

null

50

90

null

457,009

969,809

C[Al](C)C

Cl

null

ord_dataset-03ba810b7f464a06b5d8787af2e8b64e

2010-01-01T00:06:00

true

Morpholine (269 μl, 3.08 mmol) was dissolved in dichloromethane (3 ml), and under nitrogen atmosphere at room temperature, trimethylaluminium (1.03 M hexane solution, 2.99 ml, 3.08 mmol) was added. After stirring at the same temperature for 15 minutes, a solution of ethyl 4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carboxylate (I-111) (500 mg, 1.54 mmol) dissolved in dichloromethane (7 ml) was added at the same temperature. After stirring at the same temperature for 30 hours, an aqueous 1 M hydrochloric acid solution was gradually added at 0° C. The solution was extracted three times with dichloromethane. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away under reduced pressure, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=3:2) to obtain the entitled compound (460 mg, 82%) as a white solid.

Cc1c(-c2ccccc2)c(F)c2oc(C(=O)N3CCOCC3)nc2c1C#N

null

C1COCCN1

CCOC(=O)c1nc2c(C#N)c(C)c(-c3ccccc3)c(F)c2o1

null

[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C[Al](C)C.[C:11]([C:13]1[C:18]2[N:19]=[C:20]([C:22](OCC)=[O:23])[O:21][C:17]=2[C:16]([F:27])=[C:15]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:14]=1[CH3:34])#[N:12].Cl>ClCCl>[F:27][C:16]1[C:15]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[C:14]([CH3:34])[C:13]([C:11]#[N:12])=[C:18]2[C:17]=1[O:21][C:20]([C:22]([N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)=[O:23])=[N:19]2

0.25

ClCCl

null

81.8

432,970

336,425

null

ord_dataset-65c44df6676d4ce3a1874db5d7958ca9

1996-01-01T00:08:00

true

Indole-2-carboxylic acid was coupled to the resultant compound of Example 173 using the carbodiimide coupling procedure of Example 55 to provide the desired compound.

CC(C)[C@H](NC(=O)c1cc2ccccc2[nH]1)C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)[C@H](O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)c1cc2ccccc2[nH]1)C(C)C

null

N=C=N

CC(C)[C@H](N)C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)[C@H](O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N)C(C)C

O=C(O)c1cc2ccccc2[nH]1

[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([OH:12])=O.[NH2:13][C@H:14]([C:18]([NH:20][C@H:21]([C@@H:29]([OH:48])[C@H:30]([OH:47])[C@@H:31]([NH:39][C:40](=[O:46])[C@H:41]([CH:43]([CH3:45])[CH3:44])[NH2:42])[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:19])[CH:15]([CH3:17])[CH3:16].N=[C:50]=[NH:51]>>[NH:51]1[C:50]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([NH:13][C@H:14]([C:18]([NH:20][C@H:21]([C@@H:29]([OH:48])[C@H:30]([OH:47])[C@@H:31]([NH:39][C:40](=[O:46])[C@H:41]([CH:43]([CH3:44])[CH3:45])[NH:42][C:10]([C:2]1[NH:1][C:9]2[C:4]([CH:3]=1)=[CH:5][CH:6]=[CH:7][CH:8]=2)=[O:12])[CH2:32][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:19])[CH:15]([CH3:17])[CH3:16])=[O:12]

null

694,883

178,224

null

ord_dataset-4d84abdf99524e0fb6c42ab2a3300790

1988-01-01T00:10:00

true

Prepared by the method described in Example 1 from N,N'-bis(4-methoxyphenyl)thiourea (11.5 g, 40 mmoles) and acetylenedicarboxylic acid (4.6 g, 40 mmoles). Recrystallization from methanol gave the product (10.1 g), mp 184°-187° C.

COc1ccc(N=C2SC(=CC(=O)O)C(=O)N2c2ccc(OC)cc2)cc1

null

O=C(O)C#CC(=O)O

COc1ccc(NC(=S)Nc2ccc(OC)cc2)cc1

null

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[S:11])=[CH:5][CH:4]=1.[C:21]([C:26](O)=[O:27])#[C:22][C:23]([OH:25])=[O:24]>>[O:27]=[C:26]1[C:21](=[CH:22][C:23]([OH:25])=[O:24])[S:11][C:10](=[N:9][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[N:12]1[C:13]1[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=1

null

65.7

161,570

1,081,215

C[O-]

Cl

[Na+]

null

ord_dataset-afd812677c134591a99f46ce28de2524

2011-01-01T00:08:00

true

A mixture of ethyl 4,4-difluoro-3-oxobutanoate (5.0 g), butanimidamide hydrochloride (4.1 g) and sodium methoxide (28% methanol solution, 15 mL) in methanol (50 mL) was stirred overnight. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid, dried over sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale yellow oil (5.6 g, 100%).

CCCc1nc(C(F)F)cc(=O)[nH]1

null

CCOC(=O)CC(=O)C(F)F

CCCC(=N)N

null

[F:1][CH:2]([F:11])[C:3](=O)[CH2:4][C:5]([O:7]CC)=O.Cl.[C:13](=[NH:18])([NH2:17])[CH2:14][CH2:15][CH3:16].C[O-].[Na+]>CO.C(OCC)(=O)C>[F:11][CH:2]([F:1])[C:3]1[N:17]=[C:13]([CH2:14][CH2:15][CH3:16])[NH:18][C:5](=[O:7])[CH:4]=1

8

CCOC(C)=O

CO

null

98.9

3,418

1,743,480

null

ord_dataset-60a3e71da3174666a50a61dcfa611a9f

2016-01-01T00:07:00

true

To a mixture of N-(3-(1H-pyrazol-4-yl)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (50 mg, 0.081 mmol) in DCM (10 mL) was added TFA (1 mL, 12.98 mmol). The mixture was stirred at 25° C. for 2 h. The mixture was concentrated and NH4OH (0.5 mL) was added. Then the reaction residue was concentrated and purified by preparative HPLC (Column: ASB C18 150*25 mm; Mobile phase A: Water+0.1% HCl; Mobile phaseB: MeCN; Flowrate: 25 mL/min; Gradient Profile Description: 40-70 (B %)) to yield an off-white solid of N-(3-(1H-pyrazol-4-yl)-5-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)acetamide hydrochloride (6.95 mg, 0.013 mmol, 15.9% yield): 1H NMR (400 MHz, CD3OD) δ 8.16 (s, 2H), 8.06 (s, 1H), 7.82 (s, 1H), 7.62 (s, 1H), 7.48-7.42 (m, 1H), 7.41-7.34 (m, 3H), 7.33 (s, 1H), 4.15 (q, J=7.2 Hz, 2H), 3.84 (s, 2H), 1.46 (t, J=7.2 Hz, 3H). ES-LCMS m/z 501.2 (M+H). TLC (DCM/MeOH=10:1, Rf=0.2)

CCOc1cc(-c2ccc(CC(=O)Nc3cc(-c4cn[nH]c4)cc(C(F)(F)F)c3)c(F)c2)c[nH]c1=O

Cl

ClCCl

CCOc1cc(-c2ccc(CC(=O)Nc3cc(-c4cn[nH]c4)cc(C(F)(F)F)c3)c(F)c2)cnc1OCc1ccc(OC)cc1

null

[NH:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[C:8]([NH:16][C:17](=[O:45])[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:26]=[N:27][C:28]([O:34]CC5C=CC(OC)=CC=5)=[C:29]([O:31][CH2:32][CH3:33])[CH:30]=4)=[CH:21][C:20]=3[F:44])[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=2)[CH:3]=[N:2]1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:54]>>[ClH:54].[NH:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[C:8]([NH:16][C:17](=[O:45])[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:30]=[C:29]([O:31][CH2:32][CH3:33])[C:28](=[O:34])[NH:27][CH:26]=4)=[CH:21][C:20]=3[F:44])[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=2)[CH:3]=[N:2]1

2

O=C(O)C(F)(F)F

null

25

15.9

null

416,362

1,607,329

null

ord_dataset-9cecb3a8d3b9494191b28dcefea66af2

2015-01-01T00:07:00

true

The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 3-bromo-2-(isopropylthio)pyridine. MS (ESI): mass calcd. for C18H17FN4S, 340.12; m/z found, 341.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.62-8.57 (m, 1H), 8.49-8.43 (m, 1H), 8.12 (d, J=1.5, 1H), 8.04-7.93 (m, 1H), 7.45-7.39 (m, 1H), 7.34-7.30 (m, 1H), 7.29-7.22 (m, 1H), 7.11-7.03 (m, 1H), 4.69 (s, 2H), 4.17-4.00 (m, 1H), 1.37 (d, J=6.8, 6H).

CC(C)Sc1ncccc1-c1ccc(-c2cnc(N)cn2)c(F)c1

null

CC(C)Sc1ncccc1Br

CC1(C)OB(c2ccc(-c3cnc(N)cn3)c(F)c2)OC1(C)C

null

[F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[CH:19][C:20]([NH2:23])=[N:21][CH:22]=1.Br[C:25]1[C:26]([S:31][CH:32]([CH3:34])[CH3:33])=[N:27][CH:28]=[CH:29][CH:30]=1>>[F:1][C:2]1[CH:7]=[C:6]([C:25]2[C:26]([S:31][CH:32]([CH3:34])[CH3:33])=[N:27][CH:28]=[CH:29][CH:30]=2)[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[CH:19][C:20]([NH2:23])=[N:21][CH:22]=1

null

350,079

83,960

O=C([O-])O

[Na+]

null

ord_dataset-7bed824f566d4af0b51d74d386b14bd6

1981-01-01T00:07:00

true

For example, p-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate is reacted with phenylacetyl chloride in cold aqueous acetone containing sodium bicarbonate to provide p-nitrobenzyl 7-phenylacetamido-3-chloro-3-cephem-4-carboxylate.

O=C(Cc1ccccc1)NC1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(Cl)CS[C@H]12

null

O=C(Cl)Cc1ccccc1

NC1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(Cl)CS[C@H]12

null

[NH2:1][CH:2]1[C:23](=[O:24])[N:4]2[C:5]([C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=3)=[O:11])=[C:6]([Cl:9])[CH2:7][S:8][C@H:3]12.[C:25]1([CH2:31][C:32](Cl)=[O:33])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(=O)(O)[O-].[Na+]>CC(C)=O>[C:25]1([CH2:31][C:32]([NH:1][CH:2]2[C:23](=[O:24])[N:4]3[C:5]([C:10]([O:12][CH2:13][C:14]4[CH:15]=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=4)=[O:11])=[C:6]([Cl:9])[CH2:7][S:8][C@H:3]23)=[O:33])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

null

CC(C)=O

null

902,244

313,407

null

ord_dataset-abe42048f0b84fa88446cee56a31e967

1995-01-01T00:07:00

true

Dissolve ethyl-4-[4-(phenylmethyl)-1-piperazinyl]-benzo[b]thiophene-2-carboxylate (2.00 g, 5.26 mmol, prepared in example 1) in 1,2-dichloroethane (40 mL) under an atmosphere of nitrogen and cool the solution with an ice bath. Add 1-chloroethyl chloroformate (1.40 mL, 13.1 mmol) and warm the reaction to room temperature (20° C.). Stir for 30 minutes and then heat the reaction to reflux for 4.5 hours. After cooling, concentrate under vacuum, add ethanol (40 mL) to the residue, reflux for 1.5 hours under nitrogen and then stir at room temperature for 15 hours. Concentrate under vacuum and recrystallize the residue from warm ethanol (50 mL). Collect the product by suction filtration and wash with ether to provide the title compound (1.14 g) as a white solid, mp 238°-240° C.; 1H NMR (DMSO-d6) δ 9.43 (2H, bs), 8.13 (1H, s), 7.75 (1H, d, J=8.2 Hz), 7.49 (1H, t, J=7.9 Hz), 7.06 (1H, d, J=7.5 Hz), 4.37 (2H, q, J=7.1 Hz), 3.34 (8H, bs), 1.35 (3H, t, J=7.1 Hz); 13C NMR (DMSO-d6) δ 161.90, 148.81, 142.84, 132.69, 131.91, 128.35, 128.01, 117.91, 113.64, 61.50, 48.88, 43.01, 14.17; IR (KBr) 1711, 1281, 1246, 756 cm-1 ; EI/MS (70eV) 290(55%), 248(100%). IC50 =89 nM (5HT1ABinding Affinity) IC50 =47 nM (5HT1DBinding Affinity)

CCOC(=O)c1cc2c(N3CCNCC3)cccc2s1

Cl

CCOC(=O)c1cc2c(N3CCN(Cc4ccccc4)CC3)cccc2s1

CC(Cl)OC(=O)Cl

null

[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]2[CH:11]=[CH:12][CH:13]=[C:14]([N:15]3[CH2:20][CH2:19][N:18](CC4C=CC=CC=4)[CH2:17][CH2:16]3)[C:8]=2[CH:7]=1)=[O:5])[CH3:2].[Cl:28]C(OC(Cl)C)=O>ClCCCl>[ClH:28].[N:15]1([C:14]2[C:8]3[CH:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[S:10][C:9]=3[CH:11]=[CH:12][CH:13]=2)[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1

0.5

ClCCCl

null

66.3

741,529

151,850

[Na+]

null

ord_dataset-5944a40bb4504bbe8185cfdf2a811d03

1987-01-01T00:01:00

true

195.5 g of 1 was added, drop-by-drop over 45 minutes, to a stirred mixture of 164 g of anhydrous sodium acetate and 1.8 liters of dimethylformamide, at 130° C. The mixture was held at 130° C. for an additional 2.25 hours, then most of the solvent was evaporated under reduced pressure and the cooled residue and treated with sufficient of an ice/water mixture to dissolve the salts therein. The resulting mixture was extracted with ether, the extract was washed with water, and the solvent was evaporated to give 2, as a pale yellow oil, b.p.: 94° C., 0.1 Torr.

CC(=O)OCC1CN(Cc2ccccc2)C1

null

ClCC1CN(Cc2ccccc2)C1

CC(=O)[O-]

null

[CH2:1]([N:8]1[CH2:11][CH:10]([CH2:12]Cl)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:14]([O-:17])(=[O:16])[CH3:15].[Na+]>CN(C)C=O>[CH2:1]([N:8]1[CH2:11][CH:10]([CH2:12][O:17][C:14](=[O:16])[CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

2.25

CN(C)C=O

null

79,236

949,302

Cl[Sn]Cl

null

ord_dataset-3feb2a95f66e4706a4a50c977ccd9bf8

2010-01-01T00:04:00

true

Reduction of 4,6-dichloro-N-cyclopropyl-3-hydroxy-2-nitrobenzamide with tin (II) chloride hydrate using the conditions as described in Step B yielded 2-amino-4,6-dichloro-N-cyclopropyl-3-hydroxybenzamide (93%).—1H NMR (CD3OD): δ 6.67 (s, 1H), 2.86 (m, 1H), 0.79 (m, 2H), 0.62 (m, 2H).

Nc1c(O)c(Cl)cc(Cl)c1C(=O)NC1CC1

null

O=C(NC1CC1)c1c(Cl)cc(Cl)c(O)c1[N+](=O)[O-]

null

[Cl:1][C:2]1[CH:13]=[C:12]([Cl:14])[C:5]([C:6]([NH:8][CH:9]2[CH2:11][CH2:10]2)=[O:7])=[C:4]([N+:15]([O-])=O)[C:3]=1[OH:18].O.[Sn](Cl)Cl>>[NH2:15][C:4]1[C:3]([OH:18])=[C:2]([Cl:1])[CH:13]=[C:12]([Cl:14])[C:5]=1[C:6]([NH:8][CH:9]1[CH2:11][CH2:10]1)=[O:7]

null

O

null

93

null

262,533

979,884

C[O-]

[Na+]

null

ord_dataset-f886e51ba1484c76a94bce1482f1eab9

2010-01-01T00:07:00

true

A solution of sodium methoxide in MeOH (30 wt %, 202.2 g) was added to absolute EtOH (360 mL) followed by 1,3-dimethyluracil (75 g) and 2-cyano-N-phenyl-thioacetamide (Adhikari et al, Australian J. Chem., 1999, 52, 63-67) (90 g). The resulting mixture was heated at reflux for 8 h and then allowed to cool to ambient temperature overnight. The reaction mixture was then cooled to +5° and maintained at this temperature for at least an hour when the product was recovered by filtration. The filter cake was washed with cold (+5°) absolute ethanol (450 mL) and then dried to constant weight under vacuum at 45° to give the title compound as a pale pink solid (130.0 g). The product thus obtained contains residual EtOH and MeOH, estimated at 12.2 wt % by 1H nmr, corresponding to a corrected yield of 114.1 g. δH (DMSO-d6) 7.32 (2H, m), 7.27-7.18 (1H, m), 7.16 (1H, d, J 9.1 Hz), 6.92 (2H, m), 5.63 (1H, d, J 9.1 Hz). LCMS (Conditions B) (ES+) RT 2.43 minutes, 229 (M+H)+.

N#Cc1ccc(=O)n(-c2ccccc2)c1[S-]

null

N#CCC(=S)Nc1ccccc1

Cn1ccc(=O)n(C)c1=O

null

C[O-].[Na+:3].CCO.CN1[CH:15]=[CH:14][C:12](=[O:13])N(C)C1=O.[C:17]([CH2:19][C:20]([NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[S:21])#[N:18]>CO>[C:17]([C:19]1[CH:15]=[CH:14][C:12](=[O:13])[N:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:20]=1[S-:21])#[N:18].[Na+:3]

null

CCO

CO

null

25

null

731,176

264,922

null

ord_dataset-a7bd0db0684c464bb02ff6a36065fee3

1993-01-01T00:03:00

true

A mixture of 2-[(ethoxycarbonyl)amino]benzoic acid ethyl ester (65.75 g, 0.277 mol) and 2-aminoethanol (16.9 g, 0.277 mol) was refluxed for 2.5 days in 350 mL of xylenes. The reaction was cooled to room temperature and xylene was removed. Chloroform was added to the residue and a brown solid crystallized. The brown solid was filtered from the solution. The chloroform layer was extracted with water, dried (Na2SO4), filtered and the solvent was removed. The residue was placed in the freezer in isopropyl alcohol. The brown solid was triturated with isopropyl alcohol. Both produced a crystalline white solid which was dried in vacuo overnight at 80° C. This gave a total of 40.70 g (71.3% yield) of white crystalline solid, mp 250°-252° C.

O=c1[nH]c2ccccc2c(=O)n1CCO

null

NCCO

CCOC(=O)Nc1ccccc1C(=O)OCC

null

C(O[C:4](=[O:17])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12]([O:14]CC)=O)C.[NH2:18][CH2:19][CH2:20][OH:21]>>[OH:21][CH2:20][CH2:19][N:18]1[C:4](=[O:17])[C:5]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:11][C:12]1=[O:14]

null

25

null

71.3

291,874

470,644

null

ord_dataset-f1b9e9741a6a4cc68e7070df811f86bb

2000-01-01T00:07:00

true

3-Iodoaniline (8.50 mL) and diethyl ethoxymethylenemalonate (14.30 mL) are heated at 130° C. for 1 hour. The reaction is cooled to room temperature and 70 mL diphenyl ether is added. The solution is heated at 250° C. for 1.5 hours with removal of ethanol by a Dean-Stark trap. The reaction is cooled to room temperature and the resulting solid filtered, washed with hexanes, and dried. The solid is triturated in ethyl acetate to give 12.82 g of ethyl 4-hydroxy-7-iodoquinoline-3-carboxylate. A mixture of this ester (0.35 g) and 4-chlorobenzylamine (3.0 mL) are heated at 180° C. for 1 hour. The reaction is cooled to 70° C. and poured into 50 mL diethyl ether. A tan solid which crystallizes slowly out of diethyl ether is obtained. The solid is recrystallized from ethyl acetate/hexanes to give the desired product (0.22 g).

O=C(NCc1ccc(Cl)cc1)c1cnc2cc(I)ccc2c1O

null

NCc1ccc(Cl)cc1

CCOC(=O)c1cnc2cc(I)ccc2c1O

null

[OH:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([I:12])=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[C:13]([O:15]CC)=O.[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH2:24])=[CH:21][CH:20]=1>C(OCC)C>[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][NH:24][C:13]([C:3]2[CH:4]=[N:5][C:6]3[C:11]([C:2]=2[OH:1])=[CH:10][CH:9]=[C:8]([I:12])[CH:7]=3)=[O:15])=[CH:21][CH:20]=1

null

CCOCC

null

180

null

760,379

1,368,319

Oc1cc(C2CCC3(CC2)OCCO3)nc2ccnn12

null

ord_dataset-d932d1d683704a8bad3d064bcb197acc

2013-01-01T00:11:00

true

tert-Butyl 4-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate was synthesized in a manner similar to the synthesis of 7-chloro-5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazolo[1,5-a]pyrimidine, but with tert-butyl 4-(7-hydroxypyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate substituted for 5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazolo[1,5-a]pyrimidin-7-ol.

CC(C)(C)OC(=O)N1CCC(c2cc(Cl)n3nccc3n2)CC1

null

CC(C)(C)OC(=O)N1CCC(c2cc(O)n3nccc3n2)CC1

Clc1cc(C2CCC3(CC2)OCCO3)nc2ccnn12

null

[Cl:1][C:2]1[N:7]2[N:8]=[CH:9][CH:10]=[C:6]2[N:5]=[C:4]([CH:11]2[CH2:20][CH2:19]C3(OCCO3)[CH2:13][CH2:12]2)[CH:3]=1.OC1N2N=CC=C2N=C(C2CC[N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])CC2)C=1.O1C2(CCC(C3C=C(O)N4N=CC=C4N=3)CC2)OCC1>>[Cl:1][C:2]1[N:7]2[N:8]=[CH:9][CH:10]=[C:6]2[N:5]=[C:4]([CH:11]2[CH2:12][CH2:13][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:19][CH2:20]2)[CH:3]=1

null

752,773

574,695

C[C@H](N)C(=O)O

Cl

Clc1nc2ccccc2s1

null

ord_dataset-f4512fe8cd804ac79da66cbc0c2b9d42

2002-01-01T00:12:00

true

Following General Procedure B and using 2-chlorobenzothiazole (Aldrich) and L-alanine (Aldrich), N-(benzothiazol-2-yl)-L-alanine was prepared. This compound was then coupled to L-norleucine methyl ester hydrochloride (Sigma) using General Procedure D (without the 1N HCl wash) to provide for the title compound as a solid (mp=99-120° C.). The latter reaction was monitored by tlc (Rf=0.42 in 1:1 EtOAc:Hexanes) and the product was purified by preparative plate chromatography using 1:1 EtOAc:Hexanes and 5:95 MeOH:dichloromethane as the eluent.

CCCC[C@H](NC(=O)[C@H](C)Nc1nc2ccccc2s1)C(=O)OC

null

CCCC[C@H](N)C(=O)OC

C[C@H](Nc1nc2ccccc2s1)C(=O)O

null

ClC1SC2C=CC=CC=2N=1.N[C@H](C(O)=O)C.[S:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[N:19]=[C:18]1[NH:26][C@H:27]([C:29]([OH:31])=O)[CH3:28].Cl.[CH3:33][O:34][C:35](=[O:42])[C@H:36]([CH2:38][CH2:39][CH2:40][CH3:41])[NH2:37].Cl>>[CH3:33][O:34][C:35](=[O:42])[C@@H:36]([NH:37][C:29](=[O:31])[C@H:27]([CH3:28])[NH:26][C:18]1[S:17][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[N:19]=1)[CH2:38][CH2:39][CH2:40][CH3:41]

null

267,354

278,044

[BH4-]

[Na+]

null

ord_dataset-ad17798fcea64e26ba91604fca520090

1993-01-01T00:10:00

true

To a cooled (0° C.) mixture of NaBH4 (2.15 g, 0.057 mol) and isopropanol (70 mL) was added N-acetyl-4-piperidone (8.00 g, 0.057 mol). The mixture was allowed to warm to room temperature and stirred for 16 hours. CO2 was bubbled into the reaction mixture, EtOAc (120 mL) was added, and the precipitate was removed by filtration. The filtrate was concentrated to give 8.0 g (100%) of N-acetyl-4-hydroxypiperidine as a colorless oil.

CC(=O)N1CCC(O)CC1

null

CC(=O)N1CCC(=O)CC1

null

[BH4-].[Na+].[C:3]([N:6]1[CH2:11][CH2:10][C:9](=[O:12])[CH2:8][CH2:7]1)(=[O:5])[CH3:4]>C(O)(C)C>[C:3]([N:6]1[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]1)(=[O:5])[CH3:4]

16

CC(C)O

null

25

98

null

531,618

160,816

[Na+]

[OH-]

null

ord_dataset-e402405fd21e4770a14f157cb62ca439

1987-01-01T00:07:00

true

The compound of Example 28 (37.5 g, 0.10 mole) was suspended in 1,000 ml of ethanol and treated with 1N NaOH (100 ml, 0.10 mole). The mixture was warmed and stirred until clear; the ethanol and water were evaporated at reduced pressure to give 39.6 g of the white solid sodium 2-(2'-fluoro-1,1'-biphenyl-4-yl)-6-fluoro-3-methylquinoline-4-carboxylate, m.p. >360°.

Cc1c(-c2ccc(-c3ccccc3F)cc2)nc2ccc(F)cc2c1C(=O)[O-]

null

Cc1c(-c2ccc(-c3ccccc3F)cc2)nc2ccc(F)cc2c1C(=O)O

null

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:23]([CH3:24])=[C:22]([C:25]([OH:27])=[O:26])[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([F:28])[CH:20]=3)[N:15]=2)=[CH:10][CH:9]=1.[OH-].[Na+:30]>C(O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:23]([CH3:24])=[C:22]([C:25]([O-:27])=[O:26])[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([F:28])[CH:20]=3)[N:15]=2)=[CH:10][CH:9]=1.[Na+:30]

null

CCO

null

99.7

549,758

289,958

null

ord_dataset-5fb693db3950403e9ce1a516570153bf

1994-01-01T00:05:00

true

After 1 g (2.7 mmols) of 5'-O-acetyl-3'-deoxy-3'-bromoadenosine was added to 10 ml of pyridine, 418 mg (1.1 eq.) of benzoyl chloride was added to the mixture. The mixture was stirred at room temperature for 2 hours and pyridine was distilled off under reduced pressure. The residue was added to 30 ml of water followed by extraction twice with 30 ml of chloroform. After the organic solvent was washed with water and then dried over magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography to give 1.18 g (yield, 92%) of 2'-O-benzoyl-5'-O-acetyl-3'-deoxy-3'-bromoadenosine.

CC(=O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](OC(=O)c2ccccc2)[C@@H]1Br

null

O=C(Cl)c1ccccc1

CC(=O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1Br

null

[C:1]([O:4][CH2:5][C@H:6]1[O:10][C@@H:9]([N:11]2[C:20]3[N:19]=[CH:18][N:17]=[C:15]([NH2:16])[C:14]=3[N:13]=[CH:12]2)[C@H:8]([OH:21])[C@@H:7]1[Br:22])(=[O:3])[CH3:2].[C:23](Cl)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>N1C=CC=CC=1>[C:23]([O:21][C@@H:8]1[C@H:7]([Br:22])[C@@H:6]([CH2:5][O:4][C:1](=[O:3])[CH3:2])[O:10][C@H:9]1[N:11]1[C:20]2[N:19]=[CH:18][N:17]=[C:15]([NH2:16])[C:14]=2[N:13]=[CH:12]1)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

2

c1ccncc1

null

25

null

91.8

851,990

118,324

C[O-]

[Na+]

[Na]

null

ord_dataset-7a32ed4947a84db9890d8863ca9e55fb

1984-01-01T00:06:00

true

Slices of metal sodium (17.4 g, 0.755 mol) were added in small portions to methyl alcohol (250 ml) agitated at room temperature, to prepare sodium methoxide. After metal sodium pieces disappeared, a solution obtained by dissolving compound (C) (200.0 g, 0.581 mol) previously obtained, in dry toluene (600 ml) was gradually added through a dropping funnel so that the inner temperature was kept in the range of 50°~60° C. After the dropwise addition, the mixture was refluxed for 4 hours and then cooled, followed by adding water (20 ml), transfering the mixture into a separating funnel, washing separated toluene layer with water till the aqueous layer became neutral, distilling off toluene under reduced pressure, distilling the residuce under reduced pressure, and collecting a fraction having a boiling point of 105°~108° C./1.5 mmHg to obtain trans-4-methyloxymethyl-1-phenylcyclohexane (D) (100.0 g).

COC[C@H]1CC[C@H](c2ccccc2)CC1

null

Cc1ccccc1

CO

null

[Na].[CH3:2][OH:3].C[O-].[Na+].O.[C:8]1([CH3:14])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>>[CH3:2][O:3][CH2:14][C@H:8]1[CH2:13][CH2:12][C@H:11]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:10][CH2:9]1

null

O

null

25

null

87,996

553,483

C[O-]

O=C([O-])O

[Na+]

null

ord_dataset-ec9decb576c4424c9685993f6262bd9c

2002-01-01T00:07:00

true

(S)-2,3-Dihydroxy-1-propylcarbamate benzyl ester (2.11 g, 0.01 mol) in 100 ml flask was dissolved in CHCl3 (30 ml). 1-Chlorocarbonyl-1-methylethylacetate (1.8 ml, 0.013 mol) was added and stirred for 3 hours at ambient temperature. Sat. aqueous solution of NaHCO3 (20 ml) was added and extracted three times with ethyl acetate (50 ml). The organic layer was evaporated and dissolved in THF (50 ml). Sodium methoxide (0.53 g, 0.01 mol) was added and stirred for 6 hours. Sat. aqueous solution of NaHCO3 (50 ml) was added and extracted with ethyl acetate (50 ml). The organic layer was dried over anhydrous MgSO4 and evaporated to dryness. The crude product was purified by column chromatography on silica gel to give (S)-2,3-epoxy-1-propylcarbamate benzyl ester (90%, optical purity>99%ee).

O=C(NC[C@H]1CO1)OCc1ccccc1

null

O=C(NC[C@H](O)CO)OCc1ccccc1

null

[CH2:1]([O:8][C:9](=[O:16])[NH:10][CH2:11][C@H:12]([OH:15])[CH2:13]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+].C[O-].[Na+]>C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9](=[O:16])[NH:10][CH2:11][C@@H:12]1[O:15][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

3

ClC(Cl)Cl

null

25

90

null

367,426

611,395

O=C([O-])[O-]

[K+]

null

ord_dataset-5c4ee54447b84205a10f9c0473172972

2003-01-01T00:10:00

true

A mixture of 4-chloro-7-methoxy-N-(3-morpholinopropyl)quinoline-6-carboxamide (0.154 g), 4-phenoxyphenol (0.11 g), potassium carbonate (0.207 g) and DMF (4 ml) was stirred and heated to 100° C. for 16 hours. The mixture was evaporated and the residue was partitioned between ethyl acetate and water. The aqueous phase was further extracted with ethyl acetate and the combined organic extracts were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and methanol as eluent. There was thus obtained the title compound (0.13 g); NMR Spectrum: (CDCl3) 1.86 (m, 2H), 2.47 (m, 6H), 3.6 (m, 2H), 3.7 (m, 4H), 4.11 (s, 3H), 6.48 (d, 1H), 7.04-7.18 (m, 7H), 7.37 (m, 2H), 7.51 (s, 1H), 8.02 (t, 1H), 8.65 (d, 1H), 9.19 (s, 1H); Mass Spectrum M+H+ 514.

COc1cc2nccc(Oc3ccc(Oc4ccccc4)cc3)c2cc1C(=O)NCCCN1CCOCC1

null

Oc1ccc(Oc2ccccc2)cc1

COc1cc2nccc(Cl)c2cc1C(=O)NCCCN1CCOCC1

null

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:24][CH3:25])=[C:9]([C:12]([NH:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[O:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[O:26]([C:33]1[CH:38]=[CH:37][C:36]([OH:39])=[CH:35][CH:34]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:25][O:24][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([O:39][C:36]3[CH:35]=[CH:34][C:33]([O:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[CH:38][CH:37]=3)=[CH:3][CH:4]=[N:5]2)=[CH:10][C:9]=1[C:12]([NH:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)=[O:13]

null

CN(C)C=O

null

100

null

59.8

249,342

1,169,797

null

ord_dataset-d24cc23b3db94284bb83a2ccdd9eb880

2012-01-01T00:05:00

true

The title compound was prepared from 2-(4-bromo-imidazol-1-yl)-4-difluoromethyl-6-(4-trifluoromethyl-phenyl)-pyrimidine (example E.7) (0.21 g, 0.5 mmol) and commercially available 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.14 g, 0.64 mmol) according to the general procedure VI. Obtained as a yellow solid (0.031 g, 7%). MS (ISP) 433.3 [(M+H)+]; mp 253.5° C.

Nc1ccc(-c2cn(-c3nc(-c4ccc(C(F)(F)F)cc4)cc(C(F)F)n3)cn2)cn1

null

FC(F)c1cc(-c2ccc(C(F)(F)F)cc2)nc(-n2cnc(Br)c2)n1

CC1(C)OB(c2ccc(N)nc2)OC1(C)C

null

Br[C:2]1[N:3]=[CH:4][N:5]([C:7]2[N:12]=[C:11]([CH:13]([F:15])[F:14])[CH:10]=[C:9]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[N:8]=2)[CH:6]=1.[NH2:26][C:27]1[CH:32]=[CH:31][C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][N:28]=1>>[F:14][CH:13]([F:15])[C:11]1[CH:10]=[C:9]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)[N:8]=[C:7]([N:5]2[CH:6]=[C:2]([C:30]3[CH:31]=[CH:32][C:27]([NH2:26])=[N:28][CH:29]=3)[N:3]=[CH:4]2)[N:12]=1

null

272,373

1,624,021

null

ord_dataset-35c51552812941cda45194a013d34bb9

2015-01-01T00:08:00

true

Methanesulphonyl chloride (6.29 g) was added dropwise to a solution of 6-(4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenyl)-1-methyl-1H-[1,2,3]triazolo[4,5-c]-pyridine-4-carbonitrile (10.34 g) and diisopropylethylamine (22.7 ml) in DCM (300 ml) at 0° C. The mixture was stirred at room temperature for 2 hours. The DCM was removed under reduced pressure, MeOH and water were added to the residue and the solid was collected by filtration to give the expected product (11.56 g). 1H NMR (DMSO) δ: 8.96 (s, 1H), 8.49 (d, 1H), 8.46 (s, 1H), 7.51 (d, 1H), 4.46 (s, 3H), 4.39 (t, 2H), 4.34 (t, 2H), 3.18 (s, 3H), 2.21 (quin, 2H).

Cn1nnc2c(C#N)cc(-c3ccc(OCCCOS(C)(=O)=O)c(C(F)(F)F)c3)cc21

null

CS(=O)(=O)Cl

Cn1nnc2c(C#N)nc(-c3ccc(OCCCO)c(C(F)(F)F)c3)cc21

CCN(C(C)C)C(C)C

[CH3:1][S:2](Cl)(=[O:4])=[O:3].[OH:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2N=[C:21]([C:23]#[N:24])[C:20]3[N:25]=[N:26][N:27]([CH3:28])[C:19]=3[CH:18]=2)=[CH:13][C:12]=1[C:29]([F:32])([F:31])[F:30].[CH:33](N(C(C)C)CC)(C)C>C(Cl)Cl>[CH3:1][S:2]([O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:33]=[C:21]([C:23]#[N:24])[C:20]3[N:25]=[N:26][N:27]([CH3:28])[C:19]=3[CH:18]=2)=[CH:13][C:12]=1[C:29]([F:30])([F:32])[F:31])(=[O:4])=[O:3]

2

ClCCl

null

25

null

169,601

1,279,155

null

ord_dataset-d5c54236ecd94d61aaa071461bcfc426

2013-01-01T00:04:00

true

Following a procedure analogous to the procedure described in example 300 using N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]-2-fluorophenyl}-3-furansulfonamide (110 mg, 0.211 mmol), isobutylamine (77 mg, 1.056 mmol) in 1,4-dioxane (2 mL), the title compound was obtained as a yellow foam (28 mg, 0.048 mmol, 22.59%). 1H NMR (400 MHz, DMSO-d6) ppm 0.87 (d, J=6.57 Hz, 7H), 1.76 (td, J=12.00, 3.79 Hz, 3H), 1.94-2.06 (m, 2H), 3.25-3.34 (m, 2H), 3.41-3.50 (m, 2H), 3.93 (dt, J=9.66, 2.12 Hz, 2H), 5.79-6.04 (m, 1H), 6.66 (d, J=1.26 Hz, 1H), 7.20-7.41 (m, 3H), 7.41-7.56 (m, 1H), 7.81 (t, J=1.77 Hz, 1H), 8.08 (d, J=5.30 Hz, 1H), 8.28 (s, 1H), 10.31 (s, 1H); MS (ESI): 558.0 [M+H]+.

CC(C)CNc1nccc(-c2sc(C3CCOCC3)nc2-c2cccc(NS(=O)(=O)c3ccoc3)c2F)n1

null

CC(C)CN

O=S(=O)(Nc1cccc(-c2nc(C3CCOCC3)sc2-c2ccnc(Cl)n2)c1F)c1ccoc1

null

Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:34])=[C:21]([NH:25][S:26]([C:29]3[CH:33]=[CH:32][O:31][CH:30]=3)(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1.[CH2:35]([NH2:39])[CH:36]([CH3:38])[CH3:37]>O1CCOCC1>[F:34][C:20]1[C:19]([C:9]2[N:10]=[C:11]([CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[S:12][C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:39][CH2:35][CH:36]([CH3:38])[CH3:37])[N:7]=2)=[CH:24][CH:23]=[CH:22][C:21]=1[NH:25][S:26]([C:29]1[CH:33]=[CH:32][O:31][CH:30]=1)(=[O:28])=[O:27]

null

C1COCCO1

null

117,959

987,261

null

ord_dataset-35b56288528641309a040cc2b6710b61

2010-01-01T00:08:00

true

N-(1-Methylpiperidin-4-yl)-2-phenylbenzoxazole-7-carboxamide was prepared from 2-phenylbenzoxazole-7-carboxylic acid and 4-amino-1-methylpiperidine using the method outlined in Step C of Example 7. This compound was obtained in 58% yield and obtained as a white solid: mp 209-210° C.; 1H NMR (300 MHz, CDCl3) δ 8.22 (m, 1H), 8.21 (dd, J=5.7, 1.8 Hz, 1H), 8.10 (dd, J=8.1, 0.9 Hz, 1H), 7.91 (dd, J=9.9, 1.2 Hz, 1H), 7.64-7.54 (m, 3H), 7.48 (t, J=7.8, 1H), 4.26-4.17 (m, 1H), 2.93 (d, J=11.4 Hz, 2H), 2.46 (s, 3H), 2.30 (t, J=11.1 Hz, 2H), 2.22-2.17 (m, 2H), 1.85-1.73 (m, 2H); MS (ESI) m/z 336 [M+H]+

CN1CCC(NC(=O)c2cccc3nc(-c4ccccc4)oc23)CC1

null

O=C(O)c1cccc2nc(-c3ccccc3)oc12

CN1CCC(N)CC1

null

[C:1]1([C:7]2[O:8][C:9]3[C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=[CH:12][C:10]=3[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:19][CH:20]1[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]1>>[CH3:26][N:23]1[CH2:24][CH2:25][CH:20]([NH:19][C:16]([C:15]2[C:9]3[O:8][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[N:11][C:10]=3[CH:12]=[CH:13][CH:14]=2)=[O:18])[CH2:21][CH2:22]1

null

58

null

580,380

1,445,449

null

ord_dataset-a86112d52cd54525a5e36d41f18aced2

2014-01-01T00:07:00

true

The title compound (40 mg, 67%) was synthesized as an orange solid according to the method described for Example A67 (oil temp 75° C., reflux 30 min) using 5-chloro-1H-pyrrolo[3,2-b]pyridin-2(3H)-one (33.7 mg, 0.2 mmol) and 1H-indazole-6-carbaldehyde (29.2 mg, 0.2 mmol). 1H NMR (400 MHz, DMSO-d6) δ 13.56 (s, 1H), 10.90 (s, 1H), 8.93 (s, 1H), 8.37 (d, J=8.4 Hz, 1H), 8.17 (s, 1H), 7.93 (s, 1H), 7.89 (d, J=8.4 Hz, 1H), 7.39 (d, J=8.4 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H); MS ESI 297.0 [M+H]+, calcd for [C15H9ClN4O+H]+ 297.1.

O=C1Nc2ccc(Cl)nc2/C1=C\c1ccc2cn[nH]c2c1

null

O=Cc1ccc2cn[nH]c2c1

O=C1Cc2nc(Cl)ccc2N1

null

[Cl:1][C:2]1[N:7]=[C:6]2[CH2:8][C:9](=[O:11])[NH:10][C:5]2=[CH:4][CH:3]=1.[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH:21]=O)[CH:19]=2)[CH:14]=[N:13]1>>[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18](/[CH:21]=[C:8]3/[C:9](=[O:11])[NH:10][C:5]4[C:6]/3=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[CH:19]=2)[CH:14]=[N:13]1

null

67.4

null

710,981

1,021,671

[Pd]

null

ord_dataset-136cfada6ce247b4919085a57363459e

2011-01-01T00:01:00

true

100 mg (18% by mass) of 10% palladium-on-charcoal are added to a solution of 560 mg (1.88 mmol, 1 eq) of methyl (E)-3-(2-methoxy-3′-methylaminobiphenyl-4-yl)acrylate in 10 ml of methanol. The reaction mixture is stirred at room temperature under a hydrogen atmosphere for 4 hours. The reaction medium is filtered through Celite and then evaporated to dryness. 495 mg of methyl 3-(2-methoxy-3′-methylaminobiphenyl-4-yl)propanoate are obtained in oil form. Yield=88%

CNc1cccc(-c2ccc(CCC(=O)OC)cc2OC)c1

null

CNc1cccc(-c2ccc(/C=C/C(=O)OC)cc2OC)c1

null

[CH3:1][O:2][C:3]1[CH:8]=[C:7](/[CH:9]=[CH:10]/[C:11]([O:13][CH3:14])=[O:12])[CH:6]=[CH:5][C:4]=1[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH3:22])[CH:16]=1>CO.[Pd]>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH:6]=[CH:5][C:4]=1[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH3:22])[CH:16]=1

4

CO

null

25

88

null

379,247

1,412,219

O=C([O-])[O-]

[K+]

null

ord_dataset-f8e6e6a2d2bf4135b9e346456c81700f

2014-01-01T00:04:00

true

To a solution of 3-chloro-4-(trifluoromethyl)phenol (Preparation 16, 100 mg, 0.470 mmol) in DMSO (1 mL) was added potassium carbonate (0.84 mg, 0.611 mmol) and the mixture stirred for 5 minutes. 4-methylphenyl-5-chloro-2,4-difluorobenzoate (Preparation 10, 0.133 mg, 0.470 mmol) was then added and the reaction stirred under nitrogen for 3 hours. The reaction was quenched by the addition of water (2 mL) and ethyl acetate (3 ml). The organic layer was separated, dried over magnesium sulfate and concentrated in vacuo to afford a white solid that was purified using silica gel column chromatography eluting with ethyl acetate:heptane 3:97 to furnish the title compound (100 mg, 47%).

Cc1ccc(OC(=O)c2cc(Cl)c(Oc3ccc(C(F)(F)F)c(Cl)c3)cc2F)cc1

null

Oc1ccc(C(F)(F)F)c(Cl)c1

Cc1ccc(-c2c(F)c(Cl)cc(C(=O)[O-])c2F)cc1

null

[Cl:1][C:2]1[CH:3]=[C:4]([OH:12])[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].C(=O)([O-])[O-].[K+].[K+].CC1C=CC([C:26]2[C:27]([F:37])=[C:28]([CH:32]=[C:33]([Cl:36])[C:34]=2F)[C:29]([O-:31])=[O:30])=CC=1>CS(C)=O>[Cl:36][C:33]1[C:34]([O:12][C:4]2[CH:5]=[CH:6][C:7]([C:8]([F:10])([F:11])[F:9])=[C:2]([Cl:1])[CH:3]=2)=[CH:26][C:27]([F:37])=[C:28]([CH:32]=1)[C:29]([O:31][C:4]1[CH:5]=[CH:6][C:7]([CH3:8])=[CH:2][CH:3]=1)=[O:30]

0.08

CS(C)=O

null

92.7

479,171

563,580

O=C([O-])[O-]

[Na+]

null

ord_dataset-7c28974b7fcf4c9c86d5f2a42ba328a2

2002-01-01T00:09:00

true

An ethanolic solution of 2-bromo-5-chloro-6-methylthio-1-(2,3,4-tri-O-acetyl-beta-D-ribopyranosyl)-1H-benzimidazole (0.047 g, 0.09 mmol) was deprotected in a modification of General Procedure VI with 0.036 g (0.34 mmol) of sodium carbonate in 0.5 ml of water. After stirring 1 h at ambient temperature, the mixture was treated as described in General Procedure VI. The product was dried overnight in vacuo to give 2-bromo-5-chloro-6-methylthio-1-beta-D-ribopyranosyl-1H-benzimidazole (0.035 g, 0.09 mmol, 98% yield). 1H NMR (DMSO-d6) δ7.73 (s, 1H), 7.37 (s, 1H), 5.63-5.60 (d, 1H), 5.16-5.14 (m, 2H), 4.91-4.89 (d, 1H), 4.00-3.99 (m, 2H), 3.86 (m, 1H), 3.71-3.68 (m, 2H), 2.52 (s, 3H).

CSc1cc2c(cc1Cl)nc(Br)n2[C@@H]1OC[C@@H](O)[C@@H](O)[C@H]1O

null

CSc1cc2c(cc1Cl)nc(Br)n2[C@@H]1OC[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@H]1OC(C)=O

null

[Br:1][C:2]1[N:6]([C@@H:7]2[O:24][CH2:23][C@@H:18]([O:19]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]([S:30][CH3:31])[C:27]([Cl:29])=[CH:28][C:4]=2[N:3]=1.C(=O)([O-])[O-].[Na+].[Na+]>O>[Br:1][C:2]1[N:6]([C@@H:7]2[O:24][CH2:23][C@@H:18]([OH:19])[C@@H:13]([OH:14])[C@H:8]2[OH:9])[C:5]2[CH:25]=[C:26]([S:30][CH3:31])[C:27]([Cl:29])=[CH:28][C:4]=2[N:3]=1

1

O

null

25

100

null

821,498

1,516,313

[Na+]

null

ord_dataset-8c74302143c04eb9983e4b3a7ead2d72

2014-01-01T00:12:00

true

To a solution of 10-chloro-1-(2,4-dichlorophenyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazol-7-amine (29 mg, 0.075 mmol) in methanol (5.0 mL) and acetic acid (1.0 mL) was added acetaldehyde (0.05 mL, 0.84 mmol) at 0° C. The resultant mixture was stirred at 0° C. for 30 min. To the reaction mixture was added sodium triacetoxyborohydride (173 mg, 0.84 mmol) at 0° C. After stirring at room temperature for 5 h, the mixture was con concentrated in vacuo, diluted with water, and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on a silica gel eluting with a 10-50% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound (8 mg, 0.018 mmol, 24%) as a white amorphous.

CCc1c(CC)c(N)c2c(nc3n2CCCCN3c2ccc(Cl)cc2Cl)c1Cl

null

CC(=O)O[BH-](OC(C)=O)OC(C)=O

CC=O

Nc1ccc(Cl)c2nc3n(c12)CCCCN3c1ccc(Cl)cc1Cl

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH2:24])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=3[Cl:23])[CH2:12][CH2:13][CH2:14][CH2:15][N:7]21.[CH:25](=O)[CH3:26].[C:28](O[BH-](OC(=O)C)OC(=O)C)(=O)[CH3:29].[Na+]>CO.C(O)(=O)C>[Cl:1][C:2]1[C:3]([CH2:25][CH3:26])=[C:4]([CH2:28][CH3:29])[C:5]([NH2:24])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=3[Cl:23])[CH2:12][CH2:13][CH2:14][CH2:15][N:7]21

5

CC(=O)O

CO

null

25

24

null

172,715

829,409

null

ord_dataset-47bd90bf5ec74fcd99ce250a56e18c8f

2008-01-01T00:07:00

true

tert-Butyl {[6-(4-oxo-4H-1,3-benzothiazin-2-yl)-2-pyridyl]sulfonyl}acetate (0.10 g, 0.24 mmol) was dissolved in trifluoroacetic acid (5 ml), and the mixture was stirred f or 0.5 hr. Diisopropyl ether was added to the mixture. The obtained precipitates were recrystallized from ethanol to give the titled compound (0.048 g, 55%) as pale yellow crystals.

O=C(O)CS(=O)(=O)c1cccc(-c2nc(=O)c3ccccc3s2)n1

null

CC(C)(C)OC(=O)CS(=O)(=O)c1cccc(-c2nc(=O)c3ccccc3s2)n1

null

[O:1]=[C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[S:5][C:4]([C:12]2[N:17]=[C:16]([S:18]([CH2:21][C:22]([O:24]C(C)(C)C)=[O:23])(=[O:20])=[O:19])[CH:15]=[CH:14][CH:13]=2)=[N:3]1.C(OC(C)C)(C)C>FC(F)(F)C(O)=O>[O:1]=[C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[S:5][C:4]([C:12]2[N:17]=[C:16]([S:18]([CH2:21][C:22]([OH:24])=[O:23])(=[O:20])=[O:19])[CH:15]=[CH:14][CH:13]=2)=[N:3]1

0.5

CC(C)OC(C)C

O=C(O)C(F)(F)F

null

55.2

293,709

1,391,926

N

null

ord_dataset-12dc3bd21bcf44d09e5b4249afe15161

2014-01-01T00:02:00

true

30% Aqueous NH3 solution (250 μL) and 35% aqueous H2O2 solution (83 μl) are added at 0° C. to a solution of 2-((S)-6-((R)-4-(4-cyano-2,6-dimethylphenyl)-7-fluoro-2,3-dihydro-1H-inden-1-yloxy)-2,3-dihydrobenzofuran-3-yl)acetic acid (19 mg) in ethanol (2 mL). The mixture is stirred at room temperature for 12 hours, while warming to room temperature. The mixture is concentrated, diluted with water and neutralized with 4 M aqueous HCl solution. The resulting mixture is extracted with dichloromethane. The organic phase is dried (MgSO4). The solvent is evaporated to give the title compound. Yield: 19 mg; LC (method 20): tR=5.33 min; Mass spectrum (ESI+): m/z=476 [M+H]+.

Cc1cc(C(N)=O)cc(C)c1-c1ccc(F)c2c1CC[C@H]2Oc1ccc2c(c1)OC[C@H]2CC(=O)O

null

Cc1cc(C#N)cc(C)c1-c1ccc(F)c2c1CC[C@H]2Oc1ccc2c(c1)OC[C@H]2CC(=O)O

OO

null

N.[OH:2]O.[C:4]([C:6]1[CH:11]=[C:10]([CH3:12])[C:9]([C:13]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]3[C:14]=2[CH2:15][CH2:16][C@H:17]3[O:23][C:24]2[CH:36]=[CH:35][C:27]3[C@H:28]([CH2:31][C:32]([OH:34])=[O:33])[CH2:29][O:30][C:26]=3[CH:25]=2)=[C:8]([CH3:37])[CH:7]=1)#[N:5]>C(O)C>[C:4]([C:6]1[CH:11]=[C:10]([CH3:12])[C:9]([C:13]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]3[C:14]=2[CH2:15][CH2:16][C@H:17]3[O:23][C:24]2[CH:36]=[CH:35][C:27]3[C@H:28]([CH2:31][C:32]([OH:34])=[O:33])[CH2:29][O:30][C:26]=3[CH:25]=2)=[C:8]([CH3:37])[CH:7]=1)(=[O:2])[NH2:5]

12

CCO

null

25

null

201,976

1,647,584

CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1

null

ord_dataset-bcc0b01d4f58457a8733b10a099f43ba

2015-01-01T00:10:00

true

See FIG. 16(b). 1-((6-methoxy-5-methylpyrimidin-4-yl)methyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid (200 mg, 0.67 mmol) was taken in DCM (10 mL). Added 1-Propanephosphonic acid cyclic anhydride (427 mg, 1.34 mmol) followed by the addition of Triethyl amine (339 mg, 3.35 mmol) and cyclopropylmethanamine (95 mg, 1.34 mmol). The reaction mass was stirred at RT for overnight. After the completion of the reaction added water and extracted with DCM. The organic layer was washed with water and brine solution. The organic layer was separated, dried over sodium sulphate. Evaporated the organic layer to get the residue, which was purified by column chromatography to get the pure compound. Yield-74%. ES+MS m/z: 352.38 (M+1). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.02 (q, J=4.58 Hz, 2 H ) 0.18-0.31 (m, 2 H ) 0.83 (t, J=6.88 Hz, 1 H ) 2.00 (s, 3 H ) 2.98-3.11 (m, 3 H ) 3.69 (s, 3 H ) 5.43 (s, 2 H ) 7.00 (dd, J=8.29, 4.71 Hz, 1 H ) 7.68 (dd, J=8.29, 1.13 Hz, 1 H ) 7.98 (s, 1 H ) 8.17 (s, 1 H) 8.24 (dd, J=4.71, 1.13 Hz, 1 H ) 8.55 (t, J=5.75 Hz, 1 H ).

COc1ncnc(Cn2cc(C(=O)NCC3CC3)c3ncccc32)c1C

null

NCC1CC1

COc1ncnc(Cn2cc(C(=O)O)c3ncccc32)c1C

null

[CH3:1][O:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]([CH2:9][N:10]2[C:18]3[C:13](=[N:14][CH:15]=[CH:16][CH:17]=3)[C:12]([C:19]([OH:21])=O)=[CH:11]2)[C:4]=1[CH3:22].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.C(N(CC)CC)C.[CH:48]1([CH2:51][NH2:52])[CH2:50][CH2:49]1>C(Cl)Cl.O>[CH:48]1([CH2:51][NH:52][C:19]([C:12]2[C:13]3=[N:14][CH:15]=[CH:16][CH:17]=[C:18]3[N:10]([CH2:9][C:5]3[C:4]([CH3:22])=[C:3]([O:2][CH3:1])[N:8]=[CH:7][N:6]=3)[CH:11]=2)=[O:21])[CH2:50][CH2:49]1

8

ClCCl

O

CCN(CC)CC

25

null

74