HCID 58222542, compound → HCID 52916786, compound

HRID 2063379Notes

Reaction equation

HRID 2063379 reaction equation
C([O:8][C:9]1[N:14]=[C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[N:30]=[C:29]4[C:25]([N:26]=[C:27]([CH:33]5[CH2:35][CH2:34]5)[N:28]4[CH2:31][CH3:32])=[C:24]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][C@@H:37]4[CH3:42])[N:23]=3)=[CH:18][CH:17]=2)[CH:12]=[CH:11][CH:10]=1)C1C=CC=CC=1>CO.CCOC(C)=O.[OH-].[OH-].[Pd+2]>[CH:33]1([C:27]2[N:28]([CH2:31][CH3:32])[C:29]3[C:25]([N:26]=2)=[C:24]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][C@@H:37]2[CH3:42])[N:23]=[C:22]([C:19]2[CH:18]=[CH:17][C:16]([NH:15][C:13]4[NH:14][C:9](=[O:8])[CH:10]=[CH:11][CH:12]=4)=[CH:21][CH:20]=2)[N:30]=3)[CH2:34][CH2:35]1

Participants

5

Reactant 1

HCID 58222542HCID 58222542, compound

Product 1

HCID 52916786HCID 52916786, compoundYield 10.2%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-6-(benzyloxy)-N-(4-(8-cyclopropyl-9-ethyl-6-(3-methylmorpholino)-9H-purin-2-yl)phenyl)pyridin-2-amine (100 mg, 1.78 mmol) in anhydrous MeOH (4 mL) and EtOAc (4 mL) was added 20 wt % Pd(OH)2 on carbon (10.0 mg). The reaction mixture was evacuated with vacuum and purged with H2 (3×), then stirred under an atmosphere of H2 for 2 hours. The reaction mixture was then filtered through a pad of Celite®. The filtrate was concentrated in vacuo and the crude was purified by column chromotagraphy (Si-PPC, gradient 0 to 30% methanol in dichloromethane). Crystallization from ether-heptane afforded the title compound (x-1) (8.6 mg, 10.2%) as a solid. 1H NMR (DMSO-d6, 500 MHz) δ ppm 10.16 (broad s, 1H), 9.05 (broad s, 1H), 8.27 (d, J=8.7 Hz, 2H), 7.76 (broad s, 2H), 7.41 (t, J=7.9 Hz, 1H), 6.29 (broad s, 1H), 5.98 (d, J=6.3 Hz, 1H), 5.36 (broad s, 1H), 5.06 (broad s, 1H), 4.36 (q, J=7.2 Hz, 2H), 3.98 (d, J=8.5 Hz, 1H), 3.78 (d, J=11.2 Hz, 1H), 3.69 (d, J=8.7 Hz, 1H), 3.54 (t, J=10.6 Hz, 1H), 3.44 to 3.33 (m, 1H), 2.30 to 2.19 (m, 1H), 1.40 (t, J=7.1 Hz, 3H), 1.29 (d, J=6.7 Hz, 3H), 1.12 to 0.93 (m, 4H); LC-MS m/z (method C)=472.2 [M+H]+, RT=4.93 min.

Workup

  1. customThe reaction mixture was evacuated with vacuum
  2. custompurged with H2 (3×)
  3. filtrationThe reaction mixture was then filtered through a pad of Celite®
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe crude was purified by column chromotagraphy (Si-PPC, gradient 0 to 30% methanol in dichloromethane)
  6. customCrystallization from ether-heptane

Sources & evidence

ORD record
ord-ed85fd7c090540a59f9b2e5034c9cf1f
Source dataset
uspto-grants-2012_10
Patent number
US08288381B2

Reaction notes

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