Sodium Hydroxide → N-[3-[2-Benzamido-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

HRID 77585

반응식

HRID 77585 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][CH: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.[F:34][C:35]1[CH:36]=[CH:37][C:38]([C:41](O)=[O:42])=[N:39][CH:40]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[OH-].[Na+]>ClCCl.CN(C)C=O.O>[C:25]([NH:24][C:10]1[S:11][CH2:12][CH: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:41]([C:38]3[CH:37]=[CH:36][C:35]([F:34])=[CH:40][N:39]=3)=[O:42])[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

9

반응물 5

HCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27628765-fluoropyridine-2-carboxylic AcidHCID 86762771N-[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 86762773N-[3-[2-Benzamido-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

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

N-[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 (302 mg, 647 μmol) and 5-fluoropyridine-2-carboxylic acid (110 mg, 777 μmol) are combined in dichloromethane (3 mL) and dimethylformamide (0.5 mL). 1-Hydroxybenzotriazole (116 mg, 842 μmol) and then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (164 mg, 842 μmol) are added and the mixture is stirred overnight at room temperature under nitrogen. The reaction mixture is diluted with water and the pH adjusted with 1 N NaOH to ˜12 and then extracted with ethyl acetate (3×). The organic layers are combined and filtered to collect the insoluble material. The solids are washed with water and ethyl acetate and dried under vacuum to give the title compound. The organic layer from the filtrate is dried over sodium sulfate, filtered and the solvent removed in vacuo. The residue is purified over silica gel with a 20 minute 5% to 100% ethyl acetate in hexanes gradient to give additional title compound with a combined yield (275 mg, 72%). ES/MS (m/e): 590 (M+H).

후처리

  1. extractionextracted with ethyl acetate (3×)
  2. filtrationfiltered
  3. customto collect the insoluble material
  4. washThe solids are washed with water and ethyl acetate
  5. customdried under vacuum

출처 및 근거

ORD 기록
ord-258d603614084f209c8cfc42264afd78
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841293B1

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