Chlorosuccinimide → 2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylicacid(3 chloro-5-fluoro-indol-1-yl)-amide

HRID 2382033Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([NH:11][C:12]([C:14]1[C:15]([CH3:27])=[N:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)=[N:18][CH:19]=1)=[O:13])[CH:6]=[CH:5]2.C1C(=O)N([Cl:35])C(=O)C1>CC#N>[Cl:35][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=2)[N:7]([NH:11][C:12]([C:14]2[C:15]([CH3:27])=[N:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)=[N:18][CH:19]=2)=[O:13])[CH:6]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (5-fluoro-indol-1-yl)-amide (300 mg, 0.824 mmol) in MeCN (20 mL) is treated with NCS (185 mg, 1.42 mmol) and the mixture is stirred at 60° C. in a sealed flask for 2 h. The mixture is then concentrated, diluted with 10% aqueous Na2S2O8 (20 mL), and extracted with EtOAc (3×20 mL). The combined organic layer is separated, dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10%-20% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylicacid(3 chloro-5-fluoro-indol-1-yl)-amide (160 mg, 49%). MS: 399 (M+H); 1H NMR (300 MHz, CDCl3): δ 8.79 (s, 1H), 8.04 (d, 1H), 7.92 (d, 1H), 7.18 (m, 1H), 7.04 (s, 1H), 7.00 (m, 3), 6.76 (m, 1), 2.52 (s, 3H).

Workup

concentrationThe mixture is then concentrated
additiondiluted with 10% aqueous Na2S2O8 (20 mL)
extractionextracted with EtOAc (3×20 mL)
customThe combined organic layer is separated
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue is purified by silica gel chromatography
washeluting with 10%-20% EtOAc in heptane

Sources & evidence

ORD record: ord-fecef73169f24c889409fa114c77e383
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08258130B2

Reaction notes

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