Acetone → 2-[2-(Trifluoromethyl)-6-({4-[1-(trifluoromethyl)cyclopropyl]phenyl}sulfonyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]propan-2-ol

HRID 1691464Notes

Reaction equation

HRID 1691464 reaction equation
IC1[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]4([C:32]([F:35])([F:34])[F:33])[CH2:31][CH2:30]4)=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:6]=2[CH:36]=1.[CH:37]([Mg]Br)(C)C.[CH3:42][C:43]([CH3:45])=[O:44]>C1COCC1.CCOCC>[F:18][C:16]([F:17])([F:19])[C:13]1[CH:14]=[CH:15][C:9]2[CH2:8][N:7]([S:20]([C:23]3[CH:24]=[CH:25][C:26]([C:29]4([C:32]([F:35])([F:34])[F:33])[CH2:31][CH2:30]4)=[CH:27][CH:28]=3)(=[O:21])=[O:22])[C:6]3[CH:36]=[C:42]([C:43]([OH:44])([CH3:37])[CH3:45])[CH:3]=[CH:4][C:5]=3[NH:11][C:10]=2[N:12]=1

Participants

6

Reactant 3

HCID 180AcetoneHCID 866490398-Iodo-2-(trifluoromethyl)-6-({4-[1-(trifluoromethyl)cyclopropyl]phenyl}sulfonyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine2×HCID 178418365HCID 178418365, compound

Product 1

HCID 596187832-[2-(Trifluoromethyl)-6-({4-[1-(trifluoromethyl)cyclopropyl]phenyl}sulfonyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]propan-2-ol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 8-iodo-2-(trifluoromethyl)-6-({4-[1-(trifluoromethyl)-cyclopropyl]phenyl}sulfonyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (intermediate 59, 150 mg, 0.235 mmol) in THF (1.5 mL) at 0° C. was added isopropylmagnesium bromide (1.89 mmol of a 2M solution in ether). After stirred at 0° C. for 40 min, acetone (204 mg, 3.52 mmol) was added dropwise and the reaction mixture was gradually brought to rt. The reaction was quenched with saturated aqueous NH4Cl and diluted with EtOAc. The organic layer was separated and the aqueous phase was extracted with EtOAc. The combined extracts were washed with water, brine, dried over MgSO4 and concentrated. Purification of the residue via SiO2 column chromatography provided the title compound. LC/MS: m/e 572.0 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 7.65 (1H, d, J=2.1 Hz), 7.56 (1H, d, J=7.5 Hz), 7.44 (1H, dd, J=8.5, 1.6 Hz), 7.21 (2H, d, J=8.3 Hz), 7.05 (1H, d, J=7.3 Hz), 7.02 (2H, d, J=8.5 Hz), 6.77 (1H, s), 6.74 (1H, J=8.2 Hz), 4.70-4.90 (2H, s, br), 1.64 (6H, s), 1.35-1.42 (4H, m), 1.26-1.30 (4H, m).

Workup

  1. customwas gradually brought to rt
  2. customThe reaction was quenched with saturated aqueous NH4Cl
  3. additiondiluted with EtOAc
  4. customThe organic layer was separated
  5. extractionthe aqueous phase was extracted with EtOAc
  6. washThe combined extracts were washed with water, brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customPurification of the residue via SiO2 column chromatography

Sources & evidence

ORD record
ord-ad1f970cf627463082f9225133935bdf
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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