Methanol → HCID 59239180, compound

HRID 1698027Notes

Reaction equation

HRID 1698027 reaction equation
C([O:8][C:9]1[CH:14]=CN=[C:11]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[N:23]=[C:24]([N:35]4[CH2:40][CH2:39][O:38][CH2:37][C@@H:36]4[CH3:41])[C:25]4[CH2:31][CH2:30][N:29]([CH:32]([CH3:34])[CH3:33])[CH2:28][C:26]=4[N:27]=3)=[CH:18][CH:17]=2)[N:10]=1)C1C=CC=CC=1.CO.O1CC[CH2:46][CH2:45]1>[OH-].[OH-].[Pd+2]>[CH:32]([N:29]1[CH2:30][CH2:31][C:25]2[C:24]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][C@@H:36]3[CH3:41])=[N:23][C:22]([C:19]3[CH:18]=[CH:17][C:16]([NH:15][C:11]4[NH:10][C:9](=[O:8])[CH:14]=[CH:46][CH:45]=4)=[CH:21][CH:20]=3)=[N:27][C:26]=2[CH2:28]1)([CH3:34])[CH3:33]

Participants

5

Reactant 3

HCID 887MethanolHCID 8028TetrahydrofuranHCID 67177027HCID 67177027, compound

Product 1

HCID 59239180HCID 59239180, compound

Reagents, catalysts & solvents 1

HCID 9942167Palladium hydroxideCatalyst

Conditions

Temperature
40 °C

Procedure

Step 2—Synthesis of compound xa: (S)-4-(benzyloxy)-N-(4-(7-isopropyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)pyrimidin-2-amine (0.186 g, 0.337 mmol) was purged under nitrogen then added 20% Palladium hydroxide on carbon (2:8, Palladium hydroxide:carbon black, 0.14 g) followed by dry Methanol (4.85 mL, 1.20E2 mmol) Acetic acid (0.46 mL, 8.1 mmol) and dry Tetrahydrofuran (4.85 mL, 59.8 mmol) purged with hydrogen, heated at 40° C. and stirred overnight under an atmosphere of hydrogen. The reaction mixture was purged with nitrogen, added celite, filtered through celite, concentrated, chromatographed through silica gel (12 g, 0-10% MeOH in dichloromethane), and purified by HPLC. 1H NMR (400 MHz, DMSO) δ 9.24 (s, 1H), 8.24 (d, J=8.7, 2H), 8.16 (s, 1H), 7.80 (s, 1H), 7.73 (d, J=8.5, 2H), 5.86 (d, J=5.7, 1H), 4.14 (d, J=6.4, 1H), 3.87 (d, J=11.3, 1H), 3.75-3.56 (m, 7H), 3.47-3.39 (m, 2H), 2.88 (dt, J=13.0, 6.5, 1H), 2.74-2.63 (m, 3H), 2.61-2.55 (m, 2H), 2.51 (m, 1H), 1.24 (d, J=6.6, 3H), 1.08 (d, J=6.5, 6H). LC/MS-m/z+462.2 (M+H)+.

Workup

  1. custompurged with hydrogen
  2. customThe reaction mixture was purged with nitrogen
  3. additionadded celite
  4. filtrationfiltered through celite,
  5. concentrationconcentrated
  6. customchromatographed through silica gel (12 g, 0-10% MeOH in dichloromethane)
  7. custompurified by HPLC

Sources & evidence

ORD record
ord-b622f9a88eb948babbf8756df1e6ad72
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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