Sodium bis(trimethylsilyl)amide → 2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (5-methanesulfonyl-indol-1-yl)-amide

HRID 2382003Notes

Reaction equation

C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[F:11][C:12]1[CH:13]=[C:14]([C:18]2[N:23]=[C:22]([CH3:24])[C:21]([C:25](Cl)=[O:26])=[CH:20][N:19]=2)[CH:15]=[CH:16][CH:17]=1.[CH3:28][S:29]([C:32]1[CH:33]=[C:34]2[C:38](=[CH:39][CH:40]=1)[N:37]([NH2:41])[CH:36]=[CH:35]2)(=[O:31])=[O:30]>C1COCC1.N1C=CC=CC=1>[CH3:28][S:29]([C:32]1[CH:33]=[C:34]2[C:38](=[CH:39][CH:40]=1)[N:37]([NH:41][C:25]([C:21]1[C:22]([CH3:24])=[N:23][C:18]([C:14]3[CH:15]=[CH:16][CH:17]=[C:12]([F:11])[CH:13]=3)=[N:19][CH:20]=1)=[O:26])[CH:36]=[CH:35]2)(=[O:31])=[O:30]

Participants

Conditions

Temperature: 90 °C

Procedure

2.0 M of NaHMDS (sodium bis(trimethylsilyl)amide) in THF is added to a stirred solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid chloride (0.72 mmol) and 5-methanesulfonyl-indol-1-ylamine (0.72 mmol) and in anhydrous pyridine (10 mL) at rt. The reaction mixture is stirred at 90° C. overnight and then concentrated in vacuo. The residue is purified ny silica gel chromatography eluting with 1.5% MeOH in DCM to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (5-methanesulfonyl-indol-1-yl)-amide (50 mg, 8%) as a solid. MS: 425 (M+H); 1H NMR (300 MHz, CDCl3): δ 2.86 (s, 3H), 3.02 (s, 3H), 6.55 (s, H) 6.92 (d, H), 7.17-7.38 (m, 3H), 7.53 (m, H), 7.78 (s, H), 8.27 (d, H), 8.38 (d, H), 9.16 (s, H).

Workup

concentrationconcentrated in vacuo
customThe residue is purified ny silica gel chromatography
washeluting with 1.5% MeOH in DCM

Sources & evidence

ORD record: ord-c165caed26644a2e90b476843f8ef8dc
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08258130B2

Reaction notes

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