Dimethyl Sulfoxide → 6-[(4-tert-Butylphenyl)sulfonyl]-8-(1-methyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine

HRID 1691467Notes

Reaction equation

HRID 1691467 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:6]=2[CH:33]=1.[CH3:34][N:35]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[N:36]1.C(=O)([O-])[O-].[K+].[K+].CS(C)=O>O.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:29]([C:26]1[CH:25]=[CH:24][C:23]([S:20]([N:7]2[C:6]3[CH:33]=[C:2]([C:38]4[CH:37]=[N:36][N:35]([CH3:34])[CH:39]=4)[CH:3]=[CH:4][C:5]=3[NH:11][C:10]3[N:12]=[C:13]([C:16]([F:19])([F:17])[F:18])[CH:14]=[CH:15][C:9]=3[CH2:8]2)(=[O:22])=[O:21])=[CH:28][CH:27]=1)([CH3:30])([CH3:32])[CH3:31]

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 596186368-bromo-6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine2×

Product 1

HCID 596186396-[(4-tert-Butylphenyl)sulfonyl]-8-(1-methyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 8-bromo-6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (intermediate 53, 50 mg, 0.0925 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (38.5 mg, 0.185 mmol), Pd(dppf)Cl2 (22.7 mg, 0.0278 mmol), potassium carbonate (38.4 mg, 0.2775 mmol), DMSO (0.3 mL), and 3 drops of water was heated in a microwave reactor at 100° C. for 30 min. After cooling to room temperature, the reaction mixture was diluted with EtOAc, and the organic layer was separated, washed with water, brine, dried over MgSO4 and concentrated. The residue was purified via reverse phase HPLC to provide the title compound. LC/MS: m/e 542.0 (M+H)+. 1H NMR (500 MHz, CD3OD): δ 7.93 (1H, s), 7.78 (1H, s), 7.60 (2H, m), 7.40 (1H, d), 7.16 (2H, d), 7.05 (1H, d), 6.95 (1H, d), 6.90 (2H, d), 4.60-5.00 (2H, br s), 3.90 (3H, s), 1.26 (9H, s).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe organic layer was separated
  3. washwashed with water, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-05bd18ce9cf544169f218ba24a2f81e5
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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