Water → HCID 68157162, compound

HRID 243160Notes

Reaction equation

HRID 243160 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][C@@H:10]([CH3:28])[C:11]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=1[NH:21][C:22]1[CH:27]=[N:26][CH:25]=[CH:24][N:23]=1)=[O:12].Cl[C:30]1[N:38]=[CH:37][N:36]=[C:35]2[C:31]=1[N:32]=[CH:33][N:34]2[CH:39]1[CH2:44][CH2:43][CH2:42][CH2:41][O:40]1.O>CC(O)C>[F:20][C:17]1[CH:18]=[CH:19][C:14]([NH:13][C:11](=[O:12])[C@@H:10]([NH:9][C:30]2[N:38]=[CH:37][N:36]=[C:35]3[C:31]=2[N:32]=[CH:33][N:34]3[CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][O:40]2)[CH3:28])=[C:15]([NH:21][C:22]2[CH:27]=[N:26][CH:25]=[CH:24][N:23]=2)[CH:16]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157066HCID 68157066, compound

Product 1

HCID 68157162HCID 68157162, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

Triethylamine (211 μl, 1.52 mol) was added to (S)-2-amino-N-[4-fluoro-2-(pyrazin-2-ylamino)phenyl]propionamide hydrochloride (118 mg, 0.38 mmol) and 6-chloro-9-(tetrahydro-2-pyranyl)purine (109 mg, 0.45 mol) in IPA (5.0 ml) and heated at 80° C. overnight. The reaction was poured into water and the aqueous layer extracted into EtOAc (×3). The combined organic fractions were washed with brine, dried (Na2SO4) and concentrated in vacuo. The product was purified by chromatography (SiO2, 0-10% 2M ammonia methanol/DCM) to yield the title compound as a 1:1 mixture of diastereomers (100 mg, 0.21 mmol, 55%). LCMS (Method C): RT 2.55 min [M+H]+ 478.2. 1H NMR (MeOD, 400 MHz): δ 8.26 (2H, m), 7.84 (2H, m), 7.58 (2H, m), 7.32 (1H, ddd, J 11.9, 10.1, 2.8 Hz), 6.92 (1H, ddd, J 8.9, 8.1, 2.9 Hz), 5.70 (1H, m), 4.16 (1H, m), 4.80 (1H, m), 3.80 (1H, m), 2.18 (3H, m), 1.80 (2H, m), 1.61 (4H, m).

Workup

  1. extractionthe aqueous layer extracted into EtOAc (×3)
  2. washThe combined organic fractions were washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe product was purified by chromatography (SiO2, 0-10% 2M ammonia methanol/DCM)

Sources & evidence

ORD record
ord-20c34535beb34beabfa0eb88099140e7
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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