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Sodium Bicarbonate → (S)-tert-butyl (1-((3-(6-((3-fluorophenyl)amino)-4-(propylamino)nicotinamido)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

HRID 2284812
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HRID 2284812 반응식
[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:17]=[C:16]([NH:18][CH2:19][CH2:20][CH3:21])[C:12]([C:13]([OH:15])=O)=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:22][C:23]1[CH:24]=[C:25]([NH:29][C:30](=[O:42])[C@@H:31]([N:33]([CH3:41])[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH3:32])[CH:26]=[CH:27][CH:28]=1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>CN(C)C=O.C(N(CC)C(C)C)(C)C>[F:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:17]=[C:16]([NH:18][CH2:19][CH2:20][CH3:21])[C:12]([C:13]([NH:22][C:23]3[CH:24]=[C:25]([NH:29][C:30](=[O:42])[C@@H:31]([N:33]([CH3:41])[C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:39])[CH3:38])[CH3:32])[CH:26]=[CH:27][CH:28]=3)=[O:15])=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1
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참가 물질

8

반응물 5

HCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 90051717(S)-tert-butyl (1-((3-aminophenyl)amino)-1-oxopropan-2-yl)(methyl)carbamateHCID 900521806-((3-Fluorophenyl)amino)-4-(propylamino)nicotinic acid

생성물 1

HCID 90052372
(S)-tert-butyl (1-((3-(6-((3-fluorophenyl)amino)-4-(propylamino)nicotinamido)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate
수율 72.4%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 81531Diisopropylethylamine용매

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온도
40 °C

실험 절차

To a solution of 6-((3-fluorophenyl)amino)-4-(propylamino)nicotinic acid (S16, 87 mg), (S)-tert-butyl (1-((3-aminophenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (B9, 115 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (115 mg) and 1-hydroxybenzotriazole monohydrate (81 mg) in N,N-dimethylformamide (2 mL), N,N-diisopropylethylamine (157 μL) was added at room temperature, and the mixture was stirred at 40° C. for 15 hours. The reaction mixture was cooled to room temperature, and then saturated aqueous sodium hydrogencarbonate was added to the reaction mixture. The solid matter was taken by filtration, washed with water, and then purified by silica gel column chromatography (eluent, 75 to 35% hexane in ethyl acetate) to obtain (S)-tert-butyl (1-((3-(6-((3-fluorophenyl)amino)-4-(propylamino)nicotinamido)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (S17, 123 mg).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationThe solid matter was taken by filtration
  3. washwashed with water
  4. custompurified by silica gel column chromatography (eluent, 75 to 35% hexane in ethyl acetate)

출처 및 근거

ORD 기록
ord-abfd272ff19245419ccf6e286a1e439c
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09145415B2

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