Ammonia → HCID 71283218, compound

HRID 1752422Notes

Reaction equation

HRID 1752422 reaction equation
[C:1]([C:4]1[CH: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]([NH:24][C@@H:25]([CH3:30])[C:26]([O:28]C)=O)[N:5]=1)(=[O:3])[NH2:2].CO.[NH3:33]>>[NH2:33][C:26](=[O:28])[C@@H:25]([NH:24][C:6]1[N:5]=[C:4]([C:1]([NH2:2])=[O:3])[CH:9]=[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:7]=1)[CH3:30]

Participants

4

Reactant 3

HCID 222AmmoniaHCID 887MethanolHCID 71283430HCID 71283430, compound

Product 1

HCID 71283218HCID 71283218, compoundYield 81%

Procedure

A solution of (S)-methyl 2-((4-carbamoyl-6-(4-(4-fluorophenoxy)phenyl)pyrimidin-2-yl)amino)propanoate (0.911 g, 2.22 mmol) in 7M ammonia in methanol (20 mL, 140 mmol) was heated in a sealed tube for 4 days at 50° C. After cooling, the reaction mixture was evaporated in vacuo and the residue chromatographed over silica gel with 50-100% acetone in hexanes. The product fractions were evaporated in vacuo and the resulting solid triturated with 10 mL 1:1 acetone/hexanes. The solid was filtered, rinsed once with 5 mL 1:1 acetone/hexanes, and dried under vacuum at 40° C. to give (S)-2-((1-amino-1-oxopropan-2-yl)amino)-6-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide as a white powder (0.713 g, 1.80 mmol, 81% yield). 1H NMR (400 MHz, CD3OD): 8.20 (2H, d, J=8.8 Hz), 7.76 (1H, s), 7.21-7.08 (4H, m), 7.06 (2H, d, J=8.8 Hz), 4.47 (1H, br s), 1.54 (3H, d, J=7.2 Hz). LC/MS: m/z=396.1 [M+H]+.

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was evaporated in vacuo
  3. customthe residue chromatographed over silica gel with 50-100% acetone in hexanes
  4. customThe product fractions were evaporated in vacuo
  5. customthe resulting solid triturated with 10 mL 1:1 acetone/hexanes
  6. filtrationThe solid was filtered
  7. washrinsed once with 5 mL 1:1 acetone/hexanes
  8. customdried under vacuum at 40° C.

Sources & evidence

ORD record
ord-d78760e9a72a49a7a53bb16628dceeaf
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

Loading…