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

HRID 2276819노트

반응식

HRID 2276819 반응식
[OH:1][C@@H:2]([C:5]1[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[N:8]=[C:7]([C:25]([NH:27][C@@H:28]([CH3:33])[C:29]([O:31]C)=O)=[O:26])[CH:6]=1)[CH2:3][OH:4].[NH3:34]>CO>[NH2:34][C:29](=[O:31])[C@@H:28]([NH:27][C:25]([C:7]1[CH:6]=[C:5]([C@H:2]([OH:1])[CH2:3][OH:4])[N:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)=[CH:13][CH:12]=2)[N:8]=1)=[O:26])[CH3:33]

참가 물질

4

반응물 2

HCID 222AmmoniaHCID 71572320(S)-methyl 2-(6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl) pyrimidine-4-carboxamido)propanoate

생성물 1

HCID 71572210N-((S)-1-amino-1-oxopropan-2-yl)-6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide수율 87%

시약·촉매·용매 1

HCID 887Methanol용매2회

실험 절차

To (S)-methyl 2-(6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl) pyrimidine-4-carboxamido)propanoate (0.120 g, 0.263 mmol) was added MeOH (2.5 mL) and 7M NH3 in MeOH (2.5 mL, 17.5 mmol). The reaction was sealed, stirred overnight then evaporated in vacuo. MeOH was added and the reaction mixture evaporated again in vacuo. The resulting solid was triturated with 4 mL 20% EtOAc/hexanes, filtered, and rinsed once with 2 mL 20% EtOAc/hexanes. The material was dried under vacuum to give N-((S)-1-amino-1-oxopropan-2-yl)-6-((S)-1,2-dihydroxyethyl)-2-(4-(4-fluorophenoxy)phenyl)pyrimidine-4-carboxamide (Compound Example No. 16) as a pale peach-colored powder (0.099 g, 0.23 mmol. 87% yield). 1H NMR (400 MHz, DMSO-d6): 8.99 (1 H, d, J=7.7 Hz), 8.55 (2 H, d, J=9.0 Hz), 8.01 (1 H, s), 7.60 (1 H, s), 7.33-7.25 (2 H, m), 7.24-7.17 (3 H, m), 7.14 (2 H, d, J=8.8 Hz), 5.83 (1 H, d, J=5.3 Hz), 4.83 (1 H, t, J=5.9 Hz), 4.70 (1 H, q, J=3.9 Hz), 4.50 (1 H, p, J=7.2 Hz), 3.84-3.77 (1 H, m), 3.71-3.63 (1 H, m), 1.41 (3 H, d, J=7.0 Hz); LC/MS: m/z=441.2 [M+H]+.

후처리

  1. customThe reaction was sealed
  2. customthen evaporated in vacuo
  3. additionMeOH was added
  4. customthe reaction mixture evaporated again in vacuo
  5. customThe resulting solid was triturated with 4 mL 20% EtOAc/hexanes
  6. filtrationfiltered
  7. washrinsed once with 2 mL 20% EtOAc/hexanes
  8. customThe material was dried under vacuum

출처 및 근거

ORD 기록
ord-3af9332b890c4277a4dc8817e005473f
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133131B2

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