Phosgene → 2-amino-6-chloro-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one

HRID 600399Notes

Reaction equation

HRID 600399 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([NH:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[C:3]=1[NH2:16].[C:17](Cl)(Cl)=[O:18]>C1COCC1.C1(C)C=CC=CC=1>[NH2:8][C:6]1[N:5]=[C:4]2[C:3]([NH:16][C:17](=[O:18])[N:9]2[CH:10]2[CH2:11][CH2:12][O:13][CH2:14][CH2:15]2)=[C:2]([Cl:1])[N:7]=1

Participants

5

Reactant 2

HCID 6371Phosgene2×HCID 576126486-chloro-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4,5-triamine

Product 1

HCID 576126442-amino-6-chloro-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-oneYield 97%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 6-chloro-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4,5-triamine (1 g, 4.1 mmol) in 900 mL of anhydrous THF at −78° C. under Ar was added dropwise, over 40 min, a solution of phosgene in THF (3.8 mL of a 20% solution of phosgene in toluene, 7 mmol, 1.7 equiv., diluted with 26 mL of anhydrous THF). The reaction mixture was left to gradually warm up to room temperature over 16 h. It was purged with air for 30 min, then the solvent was removed in vacuo to give 1.2 g (97% yield) of the desired product (HCl salt) as a white solid. 1H NMR (300 MHz, d6-DMSO) δ, ppm: 11.40 (s, 1H), 7.00 (br s, 2H), 4.50-4.37 (m, 1H), 4.12-4.04 (m, 2H), 3.50 (app t, 2H), 2.68-2.55 (m, 2H), 1.78-1.71 (m, 2H); MS (EI) m/z 270.3 (MH)+.

Workup

  1. waitThe reaction mixture was left
  2. customIt was purged with air for 30 min
  3. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-93c41bfb29e9442ca8d3f18a0f3ef13c
Source dataset
uspto-grants-2011_03
Patent number
US07902187B2

Reaction notes

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