Acetic Acid → HCID 59239633, compound

HRID 1698028Notes

Reaction equation

HRID 1698028 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[N:23]=[C:24]([N:34]4[CH2:39][CH2:38][O:37][CH2:36][C@@H:35]4[CH3:40])[C:25]4[CH2:31][CH2:30][N:29]([CH2:32][CH3:33])[CH2:28][C:26]=4[N:27]=3)=[CH:18][CH:17]=2)[N:10]=1)C1C=CC=CC=1.CO.C(O)(=O)C.O1CCCC1>[OH-].[OH-].[Pd+2]>[CH2:32]([N:29]1[CH2:30][CH2:31][C:25]2[C:24]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][C@@H:35]3[CH3:40])=[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:13][N:12]=4)=[CH:21][CH:20]=3)=[N:27][C:26]=2[CH2:28]1)[CH3:33]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 887MethanolHCID 8028TetrahydrofuranHCID 67176764HCID 67176764, compound

Product 1

HCID 59239633HCID 59239633, compound

Reagents, catalysts & solvents 1

HCID 9942167Palladium hydroxideCatalyst

Conditions

Temperature
40 °C

Procedure

Step 3—Synthesis of compound xb: (S)-4-(benzyloxy)-N-(4-(7-ethyl-4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)pyrimidin-2-amine (0.066 g, 0.12 mmol) was purged under nitrogen then added 20% Palladium hydroxide on carbon (2:8, Palladium hydroxide:carbon black, 0.101 g) followed by dry Methanol (3.6 mL, 89 mmol), Acetic acid (0.18 mL, 3.2 mmol) and dry Tetrahydrofuran (3.6 mL, 44 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 8.23 (d, J=8.7, 2H), 7.77 (t, J=9.4, 3H), 5.85 (d, J=5.9, 1H), 4.15 (d, J=6.5, 1H), 3.87 (d, J=10.8, 1H), 3.75-3.68 (m, 1H), 3.62 (dd, J=16.9, 7.9, 4H), 3.55-3.35 (m, 2H), 2.68 (s, 3H), 2.58-2.52 (m, 3H), 1.25 (d, J=6.6, 3H), 1.11 (t, J=7.1, 3H). LC/MS-m/z+448.2 (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-fa17df36000d4840a750d6aaf1a93963
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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