2-Chloropyrimidine → N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-3-phenyl-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide

HRID 535952Notes

Reaction equation

HRID 535952 reaction equation
[CH3:1][C:2]([CH3:27])([CH3:26])[C@H:3]([NH:8][C:9]([C:11]1[N:12]=[C:13]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:14]2[CH2:19][CH2:18][NH:17][CH2:16][C:15]=12)=[O:10])[C:4]([NH:6][CH3:7])=[O:5].CCN(C(C)C)C(C)C.Cl[C:38]1[N:43]=[CH:42][CH:41]=[CH:40][N:39]=1>CN(C=O)C>[CH3:1][C:2]([CH3:27])([CH3:26])[CH:3]([NH:8][C:9]([C:11]1[N:12]=[C:13]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:14]2[CH2:19][CH2:18][N:17]([C:38]3[N:43]=[CH:42][CH:41]=[CH:40][N:39]=3)[CH2:16][C:15]=12)=[O:10])[C:4]([NH:6][CH3:7])=[O:5]

Participants

5

Reactant 3

HCID 744042-ChloropyrimidineHCID 81531DiisopropylethylamineHCID 25132789(S)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-3-phenyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide

Product 1

HCID 66931700N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-3-phenyl-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

Compound 2 (15 mg, 35 umol) was dissolved in DMF (3 mL). DIPEA was added followed by the 2-chloropyrimidine. The reaction was subjected to microwave irradiation and heated at 160° C. for 15 minutes and then for a further 5 minutes under the same conditions to drive to completion. The reaction was quenched by the addition of 2 mL of saturated aqueous NaHCO3 and extracted of DCM (2×1 mL). The combined organic layers were dried with anhydrous Na2SO4, filtered and evaporated. The residue was purified by preparative LC/MS using a 10 minute gradient from 70% water/acetonitrile to 10% water/acetonitrile with 0.1% formic acid as a modifier. The desired product, Compound 298, was isolated as a clear oil (11 mg, 68% yield). LCMS (+ESI) m/z 448.2 [M+H]+.

Workup

  1. customirradiation
  2. customThe reaction was quenched by the addition of 2 mL of saturated aqueous NaHCO3
  3. extractionextracted of DCM (2×1 mL)
  4. dry with materialThe combined organic layers were dried with anhydrous Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by preparative LC/MS
  8. waitusing a 10 minute

Sources & evidence

ORD record
ord-1f74ddd9da1b4893a9ae1f1e3779c869
Source dataset
uspto-grants-2014_10
Patent number
US08859538B2

Reaction notes

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