Dichloromethane → HCID 66730694, compound

HRID 1028013Notes

Reaction equation

HRID 1028013 reaction equation
C([N:4]([C@@H:34]([CH3:39])[C:35]([F:38])([F:37])[F:36])[S:5]([C:8]1[CH:9]=[N:10][C:11]([C:14]2[N:15]([C:28]3[N:33]=[CH:32][CH:31]=[CH:30][N:29]=3)[C:16]3[C:21]([C:22]=2[C:23]#[N:24])=[CH:20][CH:19]=[C:18]([CH:25]2[CH2:27][CH2:26]2)[CH:17]=3)=[CH:12][CH:13]=1)(=[O:7])=[O:6])C=C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(Cl)Cl>C1COCC1.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:23]([C:22]1[C:21]2[C:16](=[CH:17][C:18]([CH:25]3[CH2:26][CH2:27]3)=[CH:19][CH:20]=2)[N:15]([C:28]2[N:29]=[CH:30][CH:31]=[CH:32][N:33]=2)[C:14]=1[C:11]1[N:10]=[CH:9][C:8]([S:5]([NH:4][C@@H:34]([CH3:39])[C:35]([F:38])([F:37])[F:36])(=[O:7])=[O:6])=[CH:13][CH:12]=1)#[N:24]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydrideHCID 66730797HCID 66730797, compound

Product 1

HCID 66730694HCID 66730694, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-N-allyl-6-(3-cyano-6-cyclopropyl-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (70 mg, 0.13 mmol) and PdCl2(dppf) (10 mg, 0.013 mmol) in THF (1 mL) was added NaBH(AcO)3 (40 mg, 0.19 mmol). The mixture was stirred at room temperature for 16 hrs and CH2Cl2 (20 mL) was added. The mixture was washed with sat. aq. NH4C1 (20 mL), concentrated and purified on silica gel eluting with 0 to 10% ethyl acetate in CH2Cl2 to provide (S)-6-(3-cyano-6-cyclopropyl-1-(pyrimidin-2-yl)-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (54 mg, 83%). Melting point: 181-184° C.; MS m/z 513.2 M+H+; 1H NMR (500 MHz, CDCl3): δ8.28 (1H, s), 8.72 (1H, d, J=2.0 Hz), 8.60 (2H, d, J=9.0 Hz), 8.19 (1H, d, J=2.5 Hz), 8.18 (1H, d, J=2.0 Hz), 8.02 (1H, d, J=9.0 Hz), 7.76 (1H, s), 7.65 (1H, d, J=8.0 Hz), 7.21-7.20 (1H, m), 7.05 (1H, d, J=9.0 Hz), 5.50 (1H, s), 4.02-3.98 (1H, m), 2.02-1.96 (1H, m), 1.31 (3H, d, J=6.0 Hz), 0.98-0.96 (2H, m), 0.75-0.72 (2H, m).

Workup

  1. washThe mixture was washed with sat. aq. NH4C1 (20 mL)
  2. concentrationconcentrated
  3. custompurified on silica gel eluting with 0 to 10% ethyl acetate in CH2Cl2

Sources & evidence

ORD record
ord-e2afc495e22b4a619dc2d1beeab86e03
Source dataset
uspto-grants-2014_05
Patent number
US08735414B2

Reaction notes

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