Acetic Acid → tert-butyl ((S)-2-amino-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)-D-alaninate

HRID 1775852Notes

Reaction equation

HRID 1775852 reaction equation
C(OC([NH:11][C@@H:12]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[N:37]=[CH:36][C:35]([C:38]3[CH:43]=[CH:42][C:41]([O:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH3:51])=[CH:40][CH:39]=3)=[CH:34][N:33]=2)=[CH:28][CH:27]=1)[C:13]([NH:15][C@@H:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH3:17])=[O:14])=O)C1C=CC=CC=1.C(O)(=O)C>C1COCC1.[Pd].CCO>[NH2:11][C@@H:12]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[N:37]=[CH:36][C:35]([C:38]3[CH:43]=[CH:42][C:41]([O:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH3:51])=[CH:40][CH:39]=3)=[CH:34][N:33]=2)=[CH:28][CH:27]=1)[C:13]([NH:15][C@@H:16]([C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[CH3:17])=[O:14]

Participants

6

Reactant 2

HCID 176Acetic AcidHCID 117748655tert-butyl ((S)-2-(((benzyloxy)carbonyl)amino)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)-D-alaninate

Product 1

HCID 117748653tert-butyl ((S)-2-amino-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)-D-alaninateYield 81.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Prepared using General Procedure 18: To a stirred solution of tert-butyl ((S)-2-(((benzyloxy)carbonyl)amino)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)-D-alaninate (860 mg, 1.238 mmol) in THF (30 mL) was added palladium on carbon (10 wt %) as a slurry in EtOH (4 mL). To this mixture was added acetic acid (1 mL) and the reaction mixture was hydrogenated at 4 bar pressure at room temperature. The reaction mixture was diluted with THF (50 mL) and filtered through Celite. The crude product was loaded onto a column in 5% AcOH in MeOH/THF. The column was washed with MeOH/THF/DCM and then the product was eluted with 0.7 M ammonia in MeOH/THF/DCM. The resultant mixture was concentrated in vacuo to afford 565 mg (77%) of tert-butyl ((S)-2-amino-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)-D-alaninate INT-24 as a yellow solid. LCMS-ESI (m/z) calculated for C33H44N4O4: 560.3; no m/z observed, tR=2.61 min (Method 11).

Workup

  1. customPrepared
  2. customwas hydrogenated at 4 bar pressure at room temperature
  3. filtrationfiltered through Celite
  4. washThe column was washed with MeOH/THF/DCM
  5. washthe product was eluted with 0.7 M ammonia in MeOH/THF/DCM
  6. concentrationThe resultant mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-fb5204baa5f84e7fb33899a5a966b1bc
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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