Potassium Carbonate → (S)-tert-butyl 6-cyclopropyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-1-carboxylate

HRID 1028009Notes

Reaction equation

HRID 1028009 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH:17]3[CH2:19][CH2:18]3)[CH:15]=2)[CH:10]=[C:9]1B(O)O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:24]1[N:29]=[CH:28][C:27]([S:30]([NH:33][C@@H:34]([CH3:39])[C:35]([F:38])([F:37])[F:36])(=[O:32])=[O:31])=[CH:26][CH:25]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C.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]>[CH:17]1([C:14]2[CH:15]=[C:16]3[C:11]([CH:10]=[C:9]([C:24]4[CH:25]=[CH:26][C:27]([S:30](=[O:32])(=[O:31])[NH:33][C@@H:34]([CH3:39])[C:35]([F:37])([F:36])[F:38])=[CH:28][N:29]=4)[N:8]3[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[CH:12][CH:13]=2)[CH2:19][CH2:18]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 667309321-(tert-butoxycarbonyl)-6-cyclopropyl-1H-indol-2-ylboronic acidHCID 86665920(S)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide

Product 1

HCID 66730765(S)-tert-butyl 6-cyclopropyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-1-carboxylateYield 81.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 1-(tert-butoxycarbonyl)-6-cyclopropyl-1H-indol-2-ylboronic acid (1.10 g, 3.64 mmol), (S)-6-chloro-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (1.05 g, 3.64 mmol), PdCl2(dppf) (178 mg, 0.22 mmol), aq. K2CO3 (2 M, 5.46 mL, 10.9 mmol) in acetonitrile (8 mL) was stirred at 50° C. overnight. The solvent was then evaporated and the residue purified on silica gel eluting with 0 to 10% ethyl acetate in CH2Cl2 to provide (S)-tert-butyl 6-cyclopropyl-2-(5-(N-(1,1,1-trifluoropropan-2-yl)sulfamoyl)pyridin-2-yl)-1H-indole-1-carboxylate (1.51 g, 81% yield). MS m/z 510.3 M+H+; 1H NMR (500 MHz, CDCl3): δ 9.65 (1H, s), 8.50 (1H, m), 8.01 (1H, d, J=8.2 Hz), 7.85 (1H, s), 7.52-7.49 (2H, m), 6.98 (1H, d, J=8.2 Hz), 4.98 (1H, d, J=8.4 Hz), 4.02 (1H, m), 2.02-1.98 (1H, m), 1.34 (3H, d, J=7.5 Hz), 0.98-0.96 (2H, m), 0.76-0.72 (2H, m).

Workup

  1. customThe solvent was then evaporated
  2. customthe residue purified on silica gel eluting with 0 to 10% ethyl acetate in CH2Cl2

Sources & evidence

ORD record
ord-8e1ff1b516c545f0b5dce1fbaf5ecb84
Source dataset
uspto-grants-2014_05
Patent number
US08735414B2

Reaction notes

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