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

HRID 2278493Notes

Reaction equation

HRID 2278493 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][CH:25]=[C:26]([F:31])[C:27]=2[F:30])[NH:22]1>>[F:30][C:27]1[C:26]([F:31])=[CH:25][CH:24]=[C:23]2[C:28]=1[CH2:29][CH:21]([CH3:20])[N:22]2[C:10](=[O:12])[CH2:9][C:5]1[NH:6][C:7](=[O:8])[C:2]([F:1])=[C:3]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[N:4]=1

Participants

3

Reactant 2

HCID 13146144(+)-2-methyl-4,5-difluoro-2,3-dihydro-1H-indoleHCID 136069585Sodium (5-fluoro-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate

Product 1

HCID 1363786672-[2-((+)-4,5-difluoro-2-methyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-5-fluoro-6-morpholin-4-yl-3H-pyrimidin-4-oneYield 57.1%

Procedure

The product is prepared by following the procedure described in example 1a (step 5a) using 140 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-4,5-difluoro-2,3-dihydro-1H-indole (reference example 2a). After silica column purification: eluent 98/02 dichloromethane/methanol, 117 mg of 2-[2-((+)-4,5-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-c3adbd8419094092bb565dab20b77cf4
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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