(+)-2-methyl-5,6-difluoro-2,3-dihydro-1H-indole → 2-[2-((-)-5,6-difluoro-2-methyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-5-fluoro-6-morpholin-4-yl-3H-pyrimidin-4-one

HRID 2278491Notes

Reaction equation

HRID 2278491 reaction equation
[F:1][C:2]1[C:7](=[O:8])[NH:6][C:5]([CH2:9][C:10]([O-:12])=O)=[N:4][C:3]=1[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.[Na+].[CH3:20][CH:21]1[CH2:29][C:28]2[C:23](=[CH:24][C:25]([F:31])=[C:26]([F:30])[CH:27]=2)[NH:22]1>>[F:30][C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][C:25]=1[F:31])[N:22]([C:10](=[O:12])[CH2:9][C:5]1[NH:6][C:7](=[O:8])[C:2]([F:1])=[C:3]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[N:4]=1)[CH:21]([CH3:20])[CH2:29]2

Participants

3

Reactant 2

HCID 57388227(+)-2-methyl-5,6-difluoro-2,3-dihydro-1H-indoleHCID 136069585Sodium (5-fluoro-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate

Product 1

HCID 1363786652-[2-((-)-5,6-difluoro-2-methyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-5-fluoro-6-morpholin-4-yl-3H-pyrimidin-4-oneYield 33.4%

Procedure

The product is prepared by following the procedure described in example 1a (step 5a) using 131 mg of sodium (5-fluoro-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate obtained in step 2a of example 6a and 93 mg of (+)-2-methyl-5,6-difluoro-2,3-dihydro-1H-indole (reference example 3a). After silica column purification: eluent 98/02 dichloromethane/methanol, 64 mg of 2-[2-((−)-5,6-difluoro-2-methyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-5-fluoro-6-morpholin-4-yl-3H-pyrimidin-4-one are obtained in the form of a solid, the characteristics of which are the following:

Workup

  1. customThe product is prepared
  2. customAfter silica column purification

Sources & evidence

ORD record
ord-6603ef6a7f0d462cac0a4994e62f7864
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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