Propanenitrile, 3-amino-, (2E)-2-butenedioate (1:1) → 3-(2-Chloro-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-ylamino)propanenitrile

HRID 59094Notes

Reaction equation

HRID 59094 reaction equation
C(O)(=O)/C=C/C(O)=O.[NH2:9][CH2:10][CH2:11][C:12]#[N:13].C[O-].[Na+].[Cl:17][C:18]1[N:23]=[C:22](Cl)[CH:21]=[C:20]([CH2:25][O:26][CH2:27][C:28]([F:31])([F:30])[F:29])[N:19]=1>CO.C(#N)C>[Cl:17][C:18]1[N:23]=[C:22]([NH:13][CH2:12][CH2:11][C:10]#[N:9])[CH:21]=[C:20]([CH2:25][O:26][CH2:27][C:28]([F:31])([F:30])[F:29])[N:19]=1

Participants

6

Reactant 3

HCID 6433176Propanenitrile, 3-amino-, (2E)-2-butenedioate (1:1)HCID 10942334Sodium MethoxideHCID 1178209122,4-Dichloro-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine

Product 1

HCID 1178212213-(2-Chloro-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-4-ylamino)propanenitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 3-aminopropanenitrile fumarate (147 mg, 0.74 mmol) and sodium methoxide (1.1 mL, 0.54 mmol) in MeOH (2 mL) was added dropwise to an ice-cold solution of 2,4-dichloro-6-((2,2,2-trifluoroethoxy)methyl)pyrimidine (64 mg, 0.25 mmol) in acetonitrile (2 mL). The mixture stirred at rt over night. The mixture was heated to 50° C. for 20 h. The reaction mixture was concentrated in vacuo and the crude was partitioned between EtOAc and 1M NaOH. The organic layer was concentrated in vacuo and the residue was purified by preparative HPLC to give the title compound, 29 mg (40%).

Workup

  1. temperatureThe mixture was heated to 50° C. for 20 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe crude was partitioned between EtOAc and 1M NaOH
  4. concentrationThe organic layer was concentrated in vacuo
  5. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-631dbd8f23ed43718b3faa6ccc0ba6b0
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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