Dimethylacetamide → 6-chloro-8-methyl-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amine

HRID 600413Notes

Reaction equation

HRID 600413 reaction equation
CN(C)[C:3](=O)[CH3:4].[Cl:7][C:8]1[N:13]=[C:12]([NH2:14])[N:11]=[C:10]([NH:15][CH:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:9]=1[NH2:22].C(C(CC)(CC)C([O-])([O-])[O-])C.C(=O)(O)[O-].[Na+]>O.C(O)(=O)C>[Cl:7][C:8]1[N:13]=[C:12]([NH2:14])[N:11]=[C:10]2[C:9]=1[N:22]=[C:3]([CH3:4])[N:15]2[CH:16]1[CH2:17][CH2:18][O:19][CH2:20][CH2:21]1

Participants

7

Reactant 4

HCID 31374DimethylacetamideHCID 516892Sodium BicarbonateHCID 21875354TriethylorthoaceateHCID 576126486-chloro-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4,5-triamine

Product 1

HCID 576126526-chloro-8-methyl-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amineYield 75%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

N,N-Dimethylacetamide (8 mL) containing 0.2% (v) glacial acetic acid was added to 6-chloro-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4,5-triamine (preparation Route A) (400 mg, 1.64 mmol), followed by triethylorthoacetate (0.8 mL, 5.32 mmol, 3.2 equiv.), and the reaction mixture was heated at 160° C. in a closed vial for two days. The mixture was then poured into water, and the pH was brought to basic using a saturated solution of sodium bicarbonate. Multiple extractions with methylene chloride, washing of the combined organic layers with water, and evaporation of the solvent in vacuo gave a dark brown residue, which was purified by column chromatography (silica gel, gradual elution with 2% methanol in 4/2/1 hexanes/methylene chloride/ethyl acetate to 3% methanol in 4/2/1 hexanes/methylene chloride/ethyl acetate) to give 330 mg (75% yield) of desired product as a pale yellow solid. 1H NMR (300 MHz, CD3OD) δ, ppm: 4.67-4.57 (m, 1H), 4.11 (dd, J=11.5, 4.6 Hz, 2H), 3.61 (td, J=12.0, 1.5 Hz, 2H), 2.91-2.76 (m, 2H), 2.72 (s, 3H), 1.86 (br dd, J=12.5, 2.4 Hz, 2H); MS (EI) m/z 268.1 (MH)+.

Workup

  1. custompreparation Route A) (400 mg, 1.64 mmol)
  2. extractionextractions with methylene chloride
  3. washwashing of the combined organic layers with water, and evaporation of the solvent in vacuo
  4. customgave a dark brown residue, which
  5. customwas purified by column chromatography (silica gel, gradual elution with 2% methanol in 4/2/1 hexanes/methylene chloride/ethyl acetate to 3% methanol in 4/2/1 hexanes/methylene chloride/ethyl acetate)

Sources & evidence

ORD record
ord-282f6e9662bf45b7afee18e10ea49a68
Source dataset
uspto-grants-2011_03
Patent number
US07902187B2

Reaction notes

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