Water → HCID 178455255, compound

HRID 2169351Notes

Reaction equation

HRID 2169351 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:28](O)=[O:29])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:31]([O:38][CH2:39][CH2:40][NH:41][CH2:42][C:43]1[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=1)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32].CCCP(=O)=O.O>CN(C)C=O>[Si:31]([O:38][CH2:39][CH2:40][N:41]([CH2:42][C:43]1[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=1)[C:28]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:14]([OH:15])[N:13]=[C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]=1)=[O:29])([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]

Participants

6

Reactant 4

HCID 962WaterHCID 16167369Propylphosphoric anhydrideHCID 59688027[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-(4-fluoro-benzyl)-amineHCID 178524866HCID 178524866, compound

Product 1

HCID 178455255HCID 178455255, compoundYield 23.18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution mixture of 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid (283) (250 mg, 0.62 mmol) and [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-(4-fluoro-benzyl)-amine (8k) (210 mg, 0.74 mmol) in dimethylformamide (5 mL) was added propylphosphonic anhydride (50 wt % in ethyl acetate) (1.3 g, 1.85 mmol) at 0° C. After stirring at room temperature for 20 h, water (20 mL) was added and the mixture was extracted with ethyl acetate (3×20 mL). The combined organic part was washed with water (3×50 mL) and brine (2×30 mL) and dried and concentrated. The crude product was purified by Combi-Flash column (eluted at 20-30% ethyl acetate in hexane) to yield 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-(4-fluoro-benzyl)-amide (312) (96 mg, 23.18%) as a colourless sticky solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×20 mL)
  2. washThe combined organic part was washed with water (3×50 mL) and brine (2×30 mL)
  3. customdried
  4. concentrationconcentrated
  5. customThe crude product was purified by Combi-Flash column (eluted at 20-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-763f0ff4a6d541ca9a0beee6f07f4381
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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