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tert-Butyl [(3R)-1-{[(6S)-5-cyano-6-[4-cyano-2-(methylsulfonyl)phenyl]-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]carbonyl}piperidin-3-yl]carbamate → (4S)-3-[(3R)-3-Aminopiperidin-1-yl]carbonyl-4-[4-cyano-2-(methylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

HRID 707590
Notes
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Reaction equation

HRID 707590 reaction equation
[C:1]([C:3]1[C@@H:8]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=2[S:17]([CH3:20])(=[O:19])=[O:18])[N:7]([C:21]([N:23]2[CH2:28][CH2:27][CH2:26][C@@H:25]([NH:29]C(=O)OC(C)(C)C)[CH2:24]2)=[O:22])[C:6](=[O:37])[N:5]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:47])([F:46])[F:45])[CH:39]=2)[C:4]=1[CH3:48])#[N:2]>Cl.O1CCOCC1>[NH2:29][C@@H:25]1[CH2:26][CH2:27][CH2:28][N:23]([C:21]([N:7]2[C@H:8]([C:9]3[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=3[S:17]([CH3:20])(=[O:19])=[O:18])[C:3]([C:1]#[N:2])=[C:4]([CH3:48])[N:5]([C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:46])([F:47])[F:45])[CH:39]=3)[C:6]2=[O:37])=[O:22])[CH2:24]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 1

HCID 70255537tert-Butyl [(3R)-1-{[(6S)-5-cyano-6-[4-cyano-2-(methylsulfonyl)phenyl]-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]carbonyl}piperidin-3-yl]carbamate

Product 1

HCID 66647340(4S)-3-[(3R)-3-Aminopiperidin-1-yl]carbonyl-4-[4-cyano-2-(methylsulfonyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent
HCID 31275
1,4-Dioxane
Solvent

Procedure

tert-Butyl [(3R)-1-{[(6S)-5-cyano-6-[4-cyano-2-(methylsulfonyl)phenyl]-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidin-1(2H)-yl]carbonyl}piperidin-3-yl]carbamate (Example 12A; 56.0 mg, 0.082 mmol) was dissolved in a 4 N solution of hydrogen chloride in dioxane (2.15 ml) and stirred at RT for 60 min. The contents of the flask was then concentrated under reduced pressure, and the residue was taken up in dichloromethane (15 ml) and 2 N aqueous sodium hydroxide solution (15 ml). After extraction, the organic phase was separated off, dried over sodium sulfate and concentrated under reduced pressure. This gave 47 mg (96% of theory) of the title compound.

Workup

  1. concentrationThe contents of the flask was then concentrated under reduced pressure
  2. extractionAfter extraction
  3. customthe organic phase was separated off
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5358caf8475b4ab3b4a1ad46f99bfdbd
Source dataset
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09174997B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes