Methanol → HCID 69216015, compound

HRID 279261Notes

Reaction equation

HRID 279261 reaction equation
C(OC([NH:8][C:9]1[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][C@@H:18]1[CH2:22][CH2:21][NH:20][CH2:19]1)=[O:16])=[O:12])=O)(C)(C)C.[OH:32][C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][C:40]=1[O:41][CH3:42])[CH:36]=O.[BH3-]C#N.[Na+].CO>C(O)(=O)C>[NH2:8][C:9]1[CH:26]=[CH:25][C:24]([O:27][C:28]([F:29])([F:30])[F:31])=[CH:23][C:10]=1[C:11]([NH:13][CH2:14][C:15]([NH:17][C@@H:18]1[CH2:22][CH2:21][N:20]([CH2:36][C:35]2[CH:38]=[CH:39][C:40]([O:41][CH3:42])=[C:33]([OH:32])[CH:34]=2)[CH2:19]1)=[O:16])=[O:12]

Participants

6

Reactant 4

HCID 887MethanolHCID 12127IsovanillinHCID 5003444Sodium cyanoborohydrideHCID 69211789HCID 69211789, compound

Product 1

HCID 69216015HCID 69216015, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of (R)-3-[N-{2-(tert-butoxycarbonylamino)-5-(trifluoromethoxy)benzoyl}glycyl]aminopyrrolidine (0.050 mmol), 3-hydroxy-4-methoxybenzaldehyde (0.060 mmol), NaBH3CN (0.15 mmol), and methanol (1.3 mL) was added acetic acid (0.050 mL). The reaction mixture was stirred at 60° C. for 8 h. The mixture was cooled to room temperature, loaded onto Varian™ SCX column, and washed with CH3OH (10 mL). Product was eluted off using 2 N NH3 in CH3OH (5 mL) and concentrated. To the resulting material was added 4 N HCl in 1,4-dioxane and the solution was stirred overnight at room temperature. Concentration and preparative TLC gave (R)-3-[{N-(2-amino-5-trifluoromethoxybenzoyl)glycyl}amino]-1-(3-hydroxy-4-methoxybenzyl)pyrrolidine (Compound No. 1896) (9.1 mg, 38%): The purity was determined by RPLC/MS (93%); ESI/MS m/e 483 (M++H, C22H25F3N4O5).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with CH3OH (10 mL)
  3. washProduct was eluted off
  4. concentrationconcentrated
  5. additionTo the resulting material was added 4 N HCl in 1,4-dioxane
  6. stirringthe solution was stirred overnight at room temperature
  7. concentrationConcentration and preparative TLC

Sources & evidence

ORD record
ord-53112897e1c04947954b9eca497ab035
Source dataset
uspto-grants-2002_03
Patent number
US06362177B1

Reaction notes

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