Ammonia → (S)-6-((1-amino-1-oxopropan-2-yl)oxy)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide

HRID 1752426Notes

Reaction equation

HRID 1752426 reaction equation
[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)[N:7]=[C:6]([O:24][C@@H:25]([CH3:31])[C:26]([O:28]CC)=O)[CH:5]=1)(=[O:3])[NH2:2].CO.[NH3:34]>>[NH2:34][C:26](=[O:28])[C@@H:25]([O:24][C:6]1[N:7]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)=[CH:12][CH:11]=2)[N:9]=[C:4]([C:1]([NH2:2])=[O:3])[CH:5]=1)[CH3:31]

Participants

4

Reactant 3

HCID 222AmmoniaHCID 887MethanolHCID 71290103(S)-ethyl 2-((6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)oxy)propanoate

Product 1

HCID 71283598(S)-6-((1-amino-1-oxopropan-2-yl)oxy)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamideYield 31%

Procedure

A solution of (S)-ethyl 2-((6-carbamoyl-2-(4-(4-fluorophenoxy)phenyl)pyrimidin-4-yl)oxy)propanoate (0.762 g, 1.79 mmol) in 7M ammonia in methanol (10 mL, 70 mmol) was heated in a sealed tube overnight at 50° C. After cooling, the reaction mixture was evaporated in vacuo and the residue chromatographed over silica gel with 25-100% acetone in hexanes. The product fractions were evaporated in vacuo and the residue triturated with 5 mL MeOH. The solid was filtered and rinsed again with 2 mL MeOH. The MeOH filtrate and washings were evaporated in vacuo and triturated with 2 mL MeOH, filtered, and rinsed again with 1 mL MeOH. The first and second batches of solid were combined and dried under vacuum at 40° C. to give (S)-6-((1-amino-1-oxopropan-2-yl)oxy)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide as a white powder (0.220 g, 0.555 mmol, 31% yield). 1H NMR (400 MHz, DMSO-d6): 8.59 (2H, d, J=8.8 Hz), 8.50 (1H, s), 7.96 (1H, s), 7.69 (1H, s), 7.33-7.25 (2H, m), 7.24 (1H, s), 7.23-7.15 (3H, m), 7.06 (2H, d, J=8.8 Hz), 5.36 (1H, q, J=6.8 Hz), 1.52 (3H, d, J=7.0 Hz). LC/MS: m/z=397.0 [M+H]+.

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was evaporated in vacuo
  3. customthe residue chromatographed over silica gel with 25-100% acetone in hexanes
  4. customThe product fractions were evaporated in vacuo
  5. customthe residue triturated with 5 mL MeOH
  6. filtrationThe solid was filtered
  7. washrinsed again with 2 mL MeOH
  8. customThe MeOH filtrate and washings were evaporated in vacuo
  9. customtriturated with 2 mL MeOH
  10. filtrationfiltered
  11. washrinsed again with 1 mL MeOH
  12. customdried under vacuum at 40° C.

Sources & evidence

ORD record
ord-5ef70aab43704fc2bf8cd6f180fbe4c5
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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