MTBE methanol → 4-{(4S)-6-methyl-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-2,3,4,5,6,7-hexahydro-1H-pyrrolo[3,4-d]pyrimidin-4-yl}-3-(methylsulfonyl)benzonitrile

HRID 707580Notes

Reaction equation

HRID 707580 reaction equation
CC(OC)(C)C.[CH3:7][OH:8].[C:9]([C:11]1[CH:16]=[CH:15][C:14]([C@@H:17]2[C:22](C#N)=[C:21]([CH3:25])[N:20]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=3)C(=O)[N:18]2S(C2CC2)(=O)=O)=[C:13]([S:43]([CH3:46])(=[O:45])=[O:44])[CH:12]=1)#[N:10].[CH3:47][OH:48].[C:49](#[N:51])C.CC(OC)(C)C>>[CH3:49][N:51]1[C:7](=[O:8])[C:22]2[C@@H:17]([C:14]3[CH:15]=[CH:16][C:11]([C:9]#[N:10])=[CH:12][C:13]=3[S:43]([CH3:46])(=[O:45])=[O:44])[NH:18][C:47](=[O:48])[N:20]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=3)[C:21]=2[CH2:25]1

Participants

4

Reactant 3

HCID 22277986MTBE methanol2×HCID 44133411(4S)-4-[4-Cyano-2-(methylsulfonyl)phenyl]-6-methyl-3-(cyclopropylsulfonyl)-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrileHCID 131729987methanol acetonitrile MTBE

Product 1

HCID 581336784-{(4S)-6-methyl-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-2,3,4,5,6,7-hexahydro-1H-pyrrolo[3,4-d]pyrimidin-4-yl}-3-(methylsulfonyl)benzonitrile

Procedure

(rac)-4-{6-Methyl-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-2,3,4,5,6,7-hexahydro-1H-pyrrolo[3,4-d]pyrimidin-4-yl}-3-(methylsulfonyl)benzonitrile (Example 34, 190 mg) was separated into the enantiomers by preparative HPLC chromatography on a chiral phase [column: Daicel Chiralpak IC, 5 μm, 250 mm×20 mm; sample preparation: the sample was dissolved in 70 ml of methanol/acetonitrile/MTBE 25:10:35; injection volume: 1 ml; mobile phase: MTBE/methanol 75:25 (0-7 min); flow rate: 15 ml/min; temperature: 30° C.; detection: 220 nm]. This gave 97 mg (100% of theory, >99.0% ee) of the 4S enantiomer. The enantiomeric excess (ee value) was determined chromatographically [column: Daicel Chiralpak IC, 5 μm, 250 mm×4.6 mm; mobile phase: MTBE/methanol 75:25; flow rate: 1 ml/min; temperature: 25° C.; detection: 220 nm; Rt=6.62 min].

Workup

  1. custom(rac)-4-{6-Methyl-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-2,3,4,5,6,7-hexahydro-1H-pyrrolo[3,4-d]pyrimidin-4-yl}-3-(methylsulfonyl)benzonitrile (Example 34, 190 mg) was separated into the enantiomers by preparative HPLC chromatography on a chiral phase [column
  2. customsample preparation
  3. custom30° C.

Sources & evidence

ORD record
ord-7d171973b22444308727f752547d4ddf
Source dataset
uspto-grants-2015_11
Patent number
US09174997B2

Reaction notes

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