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

HRID 2276819ノート

反応式

HRID 2276819 の反応式
[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]

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-3af9332b890c4277a4dc8817e005473f
出典データセット
uspto-grants-2015_09
特許番号
US09133131B2

反応ノート

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