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Hydrochloric Acid → N-[3-[(4aR,7aS)-2-Amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-fluoro-pyridine-2-carboxamide hydrochloride

HRID 876745
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HRID 876745 반응식
[NH2:1][C:2]1[S:3][CH2:4][CH:5]2[CH2:10][N:9]([C:11]3[N:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=3)[CH2:8][C:6]2([C:18]2[CH:19]=[C:20]([NH:25][C:26]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][N:29]=3)=[O:27])[CH:21]=[CH:22][C:23]=2[F:24])[N:7]=1.CO.[ClH:37].C(OCC)C>C(=O)=O.ClCCl>[ClH:37].[NH2:1][C:2]1[S:3][CH2:4][C@@H:5]2[CH2:10][N:9]([C:11]3[N:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=3)[CH2:8][C@:6]2([C:18]2[CH:19]=[C:20]([NH:25][C:26]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][N:29]=3)=[O:27])[CH:21]=[CH:22][C:23]=2[F:24])[N:7]=1
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참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 887Methanol3회HCID 3283Diethyl EtherHCID 86762779N-[3-[2-Amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-fluoro-pyridine-2-carboxamide

생성물 1

HCID 90402016N-[3-[(4aR,7aS)-2-Amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-fluoro-pyridine-2-carboxamide hydrochloride
수율 38%

시약·촉매·용매 2

HCID 280Carbon Dioxide용매2회HCID 6344Dichloromethane용매

실험 절차

Racemic N-[3-[2-amino-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-fluoro-pyridine-2-carboxamide (451 mg, 929 μmol) is chirally purified by SFC (Column: Chiralcel OD-H (5 um), 2.1×25 cm; eluent: 40% methanol (0.2% isopropylamine) in CO2; flow 70 mL/min at UV 225 nm). Chiral analysis of the first eluting isomer: Column: Chiralcel OD-H (5 μm), 4.6×150 mm; eluent: 40% methanol (0.2% isopropylamine) in CO2; flow 5 mL/min at UV 225 nm confirms the enantiomerically enriched (>99% ee) enantiomer with Rt=1.01 minutes (175 mg, 360 μmoles). This material (free base, isomer 1) is dissolved in dichloromethane (1 mL) and methanol (0.5 mL) and 1 M hydrogen chloride in diethyl ether (0.36 mL, 360 μmoles) is added. The solvent is removed in vacuo to give the title compound (183 mg, 38%). ES/MS (m/e): 486 (M+H).

후처리

  1. customThe solvent is removed in vacuo

출처 및 근거

ORD 기록
ord-d3f680d668244c66972031f6a89fcf95
출처 데이터셋
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08987254B2

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