Sodium Hydroxide → N-[3-[(4aR,7aS)-2-Benzamido-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-cyano-pyridine-2-carboxamide

HRID 77590

반응식

HRID 77590 반응식
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:33])=[C:6]([C@:8]23[CH2:16][N:15]([C:17]4[N:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=4)[CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:24][C:25](=[O:32])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:9]3)[CH:7]=1.[C:34]([C:36]1[CH:37]=[CH:38][C:39]([C:42](O)=[O:43])=[N:40][CH:41]=1)#[N:35].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[OH-].[Na+]>ClCCl.CN(C=O)C.O.C(OCC)(=O)C>[C:25]([NH:24][C:10]1[S:11][CH2:12][C@@H:13]2[CH2:14][N:15]([C:17]3[N:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=3)[CH2:16][C@:8]2([C:6]2[CH:7]=[C:2]([NH:1][C:42]([C:39]3[CH:38]=[CH:37][C:36]([C:34]#[N:35])=[CH:41][N:40]=3)=[O:43])[CH:3]=[CH:4][C:5]=2[F:33])[N:9]=1)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

참가 물질

10

반응물 5

HCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 124007345-Cyanopyridine-2-carboxylic acidHCID 86762775N-[(4aR,7aS)-7a-(5-Amino-2-fluoro-phenyl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide

생성물 1

HCID 86762778N-[3-[(4aR,7aS)-2-Benzamido-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-7a-yl]-4-fluoro-phenyl]-5-cyano-pyridine-2-carboxamide수율 57.2%

시약·촉매·용매 4

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

N-[(4aR,7aS)-7a-(5-Amino-2-fluoro-phenyl)-6-(5-fluoropyrimidin-2-yl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (0.180 g, 0.39 mmol, isomer 1) is dissolved in a mixture of dichloromethane (2 mL) and DMF (0.25 mL). 5-Cyanopyridine-2-carboxylic acid (114 mg, 0.77 mmol), 1-hydroxybenzotriazole (106 mg, 0.77 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (150 mg, 0.77 mmol) are added and the reaction is stirred at room temperature overnight. The mixture is diluted with water (10 mL), ethyl acetate (10 mL) and added to a solution of 1 N NaOH (100 mL). The mixture is extracted with EtOAc (2×100 mL) and the organic layers are combined and washed with brine. The organic layer is dried over MgSO4, filtered and concentrated. The residue is purified over silica gel chromatography using a 0-100% ethyl acetate/hexanes gradient to give the title compound (133 mg, 57%). ES/MS (m/e): 597 (M+H).

후처리

  1. extractionThe mixture is extracted with EtOAc (2×100 mL)
  2. washwashed with brine
  3. dry with materialThe organic layer is dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified over silica gel chromatography

출처 및 근거

ORD 기록
ord-9784645d25d147ac9a61fef2f55ceaab
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841293B1

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