Hydrochloric Acid → 2-((1R,2R)-1-amino-2-hydroxypropyl)-5-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid

HRID 1056231노트

반응식

HRID 1056231 반응식
[CH:1]1([NH:4][C:5]2[C:6]([CH3:28])=[N:7][C:8]3[C:13]([N:14]=2)=[C:12]([C:15]2[NH:19][C:18]4[C@H:20]([C@H:24]([OH:26])[CH3:25])[NH:21][C:22](=[O:23])[C:17]=4[CH:16]=2)[C:11]([F:27])=[CH:10][CH:9]=3)[CH2:3][CH2:2]1.[Li+].[OH-:30].Cl>O1CCOCC1.O>[NH2:21][C@H:20]([C:18]1[NH:19][C:15]([C:12]2[C:11]([F:27])=[CH:10][CH:9]=[C:8]3[C:13]=2[N:14]=[C:5]([NH:4][CH:1]2[CH2:2][CH2:3]2)[C:6]([CH3:28])=[N:7]3)=[CH:16][C:17]=1[C:22]([OH:23])=[O:30])[C@H:24]([OH:26])[CH3:25]

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 89783316(6R)-2-(3-(cyclopropylamino)-6-fluoro-2-methyl-5-quinoxalinyl)-6-((1R)-1-hydroxyethyl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one

생성물 1

HCID 897937832-((1R,2R)-1-amino-2-hydroxypropyl)-5-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid

시약·촉매·용매 2

HCID 962Water촉매HCID 312751,4-Dioxane용매3회

반응 조건

온도
100 °C

실험 절차

The yellow foam (352b) (184.5 mg) in 1,4-dioxane (6.0 mL) was treated with 1.0 M aq. LiOH (3.0 mL, 3.0 mmol). The mixture was heated at 100° C. for 16 h. The mixture was lyophilized to give a yellow solid containing m/z (ESI, +ve) 614.1 (M+H). The yellow solid was dissolved in 1 mL of dioxane and treated with a solution of 4 M HCl in 1,4-dioxane (5 mL) with a few drops of water added to aid solubility. The mixture was stirred at RT for 4 h, after which time bis-deprotection was observed by LC-MS. The mixture was lyophilized to give 2-((1R,2R)-1-amino-2-hydroxypropyl)-5-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid (352c) as a brown solid. A solution of the 2-((1R,2R)-1-amino-2-hydroxypropyl)-5-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylic acid (352c) in DMF (3.0 mL) was treated with TEA (0.20 mL, 1.44 mmol) followed by PyBOP (NovaBiochem) (300 mg, 0.57 mmol). The mixture was stirred at RT for 16 h. The mixture was concentrated, dissolved in DMSO (5.0 mL), and purified by preparative HPLC (Gradient: 10-100% MeCN in H2O, modified with 0.1% TFA) to give (R)-2-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-6-((R)-1-hydroxyethyl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one bis(2,2,2-trifluoroacetate) (352) (54 mg, 0.089 mmol) as a red gum. LC-MS m/z 382.1, [M+H]+; 19F NMR (DMSO-d6; 376 MHz): δ −108.08 (s, 1F), −74.95 (s, 6F).

후처리

  1. customto give a yellow solid
  2. additioncontaining m/z (ESI, +ve) 614.1 (M+H)
  3. additionadded

출처 및 근거

ORD 기록
ord-45dcb8a5c7fe4b2480929524a76cce48
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394297B2

반응 노트

불러오는 중…