Potassium Phosphate, Tribasic → HCID 66730797, compound

HRID 1028012Notes

Reaction equation

HRID 1028012 reaction equation
[CH2:1]([N:4]([C@@H:28]([CH3:33])[C:29]([F:32])([F:31])[F:30])[S:5]([C:8]1[CH:9]=[N:10][C:11]([C:14]2[NH:15][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])[CH:2]=[CH2:3].Br[C:35]1[N:40]=[CH:39][CH:38]=[CH:37][N:36]=1.CN[C@@H]1CCCC[C@H]1NC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[CH2:1]([N:4]([C@@H:28]([CH3:33])[C:29]([F:31])([F:30])[F:32])[S:5]([C:8]1[CH:9]=[N:10][C:11]([C:14]2[N:15]([C:35]3[N:40]=[CH:39][CH:38]=[CH:37][N:36]=3)[C:16]3[C:21]([C:22]=2[C:23]#[N:24])=[CH:20][CH:19]=[C:18]([CH:25]2[CH2:26][CH2:27]2)[CH:17]=3)=[CH:12][CH:13]=1)(=[O:6])=[O:7])[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 783452-BromopyrimidineHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 66731038HCID 66731038, compound

Product 1

HCID 66730797HCID 66730797, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-N-allyl-6-(3-cyano-6-cyclopropyl-1H-indol-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-sulfonamide (140 mg, 0.30 mmol), 2-bromo-pyrimidine (98 mg, 0.59 mmol), copper (I) iodide (11 mg, 0.06 mmol), (1R,2R)-N1,N2-dimethylcyclohexane-1,2-diamine (0.02 mL, 0.12 mmol), and K3PO4 (134 mg, 0.60 mmol) in toluene was stirred at 100° C. for 16 hrs. The mixture was then filtered through celite and the solvent evaporated. The residue was purified on silica gel eluting with 0 to 10% ethyl acetate in CH2Cl2 to provide (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 (140 mg, 86%). MS m/z 553.3 M+H+; 1H NMR (500 MHz, CDCl3): δ 8.65 (1H, d, J=3.0 Hz), 8.62 (2H, d, J=4.0 Hz), 8.14 (1H, dd, J=4.0, 8.0 Hz), 8.01 (1H, d, J=9.0 Hz), 7.75 (1H, s), 7.64 (1H, d, J=7.5 Hz), 7.21-7.19 (1H, m), 7.04 (1H, d, J=9.0 Hz), 5.60 (1H, m), 5.28-5.25 (2H, m), 4.50 (1H, m), 3.86 (1H, d, J=6.5 Hz), 2.02-1.96 (1H, m), 1.32 (3H, d, J=8.5 Hz), 0.98-0.96 (2H, m), 0.75-0.72 (2H, m).

Workup

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

Sources & evidence

ORD record
ord-6eae5af1ff35448eae24ad070fb8160a
Source dataset
uspto-grants-2014_05
Patent number
US08735414B2

Reaction notes

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