Water → (1S)-5-(1-Methyl-6-oxo-1,6-dihydro-[4,4']bipyrimidinyl-2-yl)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 271309Notes

Reaction equation

HRID 271309 reaction equation
C(N(CC)CC)C.Cl[C:9]1[N:10]([CH3:22])[C:11](=[O:21])[CH:12]=[C:13]([C:15]2[CH:20]=[CH:19][N:18]=[CH:17][N:16]=2)[N:14]=1.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH:34]2[CH2:36][C@H:31]1[CH2:32][NH:33]2)=[O:29])([CH3:26])([CH3:25])[CH3:24].O>O1CCCC1>[C:23]([O:27][C:28]([N:30]1[CH2:35][CH:34]2[CH2:36][C@H:31]1[CH2:32][N:33]2[C:9]1[N:10]([CH3:22])[C:11](=[O:21])[CH:12]=[C:13]([C:15]2[CH:20]=[CH:19][N:18]=[CH:17][N:16]=2)[N:14]=1)=[O:29])([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 179544602-Chloro-3-methyl-6-(pyrimidin-4-YL)pyrimidin-4-oneHCID 66592084(1S,4S)-(-)-2-Boc-2,5-diazabicyclo[2.2.1]heptane

Product 1

HCID 66915669(1S)-5-(1-Methyl-6-oxo-1,6-dihydro-[4,4']bipyrimidinyl-2-yl)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl esterYield 99.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture containing 1.95 ml (14 mmol) of triethylamine, 2.45 g (11 mmol) of 2-chloro-1-methyl-1H-[4,4′]bipyrimidinyl-6-one, 2.58 g (13 mmol) of (1S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester in 100 ml of anhydrous tetrahydrofuran was stirred at room temperature for 2 h. Water was added to the cooled mixture and the resulting solution extracted with ethyl acetate. The combined extracts were washed with saturated aqueous ammonium chloride and evaporated. The crude product was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 100/0 to 98/2 to afford 4.2 g of pure product as a white solid.

Workup

  1. extractionthe resulting solution extracted with ethyl acetate
  2. washThe combined extracts were washed with saturated aqueous ammonium chloride
  3. customevaporated
  4. customThe crude product was purified by chromatography on silica gel eluting with a mixture of dichloromethane/methanol in the proportions 100/0 to 98/2

Sources & evidence

ORD record
ord-c7c9edeb2ca4450ba0800d17cb2b1925
Source dataset
uspto-grants-2008_11
Patent number
US07452897B2

Reaction notes

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