Sodium Carbonate → N-(3,4-Difluorobenzyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-6-(pyrimidin-5-yl)-1H-indole-3-carboxamide

HRID 40156

Reaction equation

FC(F)(F)S(O[C:7]1[CH:15]=[C:14]2[C:10]([C:11]([C:26](=[O:37])[NH:27][CH2:28][C:29]3[CH:34]=[CH:33][C:32]([F:35])=[C:31]([F:36])[CH:30]=3)=[C:12]([CH:23]([CH3:25])[CH3:24])[N:13]2[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:9][CH:8]=1)(=O)=O.[Li+].[Cl-].C([O-])([O-])=O.[Na+].[Na+].[N:48]1[CH:53]=[C:52](B(O)O)[CH:51]=[N:50][CH:49]=1>C1(C)C=CC=CC=1.CO.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:36][C:31]1[CH:30]=[C:29]([CH:34]=[CH:33][C:32]=1[F:35])[CH2:28][NH:27][C:26]([C:11]1[C:10]2[C:14](=[CH:15][C:7]([C:52]3[CH:53]=[N:48][CH:49]=[N:50][CH:51]=3)=[CH:8][CH:9]=2)[N:13]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[C:12]=1[CH:23]([CH3:24])[CH3:25])=[O:37]

Participants

Conditions

Temperature: 80 °C

Procedure

General Procedure BB. To a solution of 3-(3,4-difluorobenzylcarbamoyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indol-6-yl trifluoromethanesulfonate (Compound 202, 33 mg, 0.06 mmol) in toluene (8 ml) and MeOH (1 ml) at 25° C., bubbled with argon then added LiCl (8 mg, 0.18 mmol), Na2CO3 (aqueous) (2M, 0.1 ml), Pd(PPh3)4 (3.4 mg, 0.003 mmol), and 5-pyrimidine boronic acid (11 mg, 0.09 mmol). The reaction was stirred for 12 h at 80° C., diluted with EtOAc, the organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes) to yield the title compound as a white solid.

Workup

washthe organic layer was washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customThe residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes)

Sources & evidence

ORD record: ord-01f38e98f9bf44d4985ed98fa96bc0b8
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524917B2

Linked notes

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