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Dimethylamine → 4-(2-Fluoro-4-hydroxymethyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

HRID 1643574
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HRID 1643574 반응식
[CH3:1][NH:2][CH3:3].[BH3-]C#N.[Na+].[CH3:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[CH:27]=[C:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([CH:35]=[O:36])=[CH:31][C:30]=3[F:37])[C:20]3[CH2:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=3[CH:18]=2)=[O:16])=[N:10]1>CO>[CH3:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[CH:27]=[C:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([CH2:35][N:2]([CH3:3])[CH3:1])=[CH:31][C:30]=3[F:37])[C:20]3[CH2:21][C:22]([CH3:24])([CH3:25])[O:23][C:19]=3[CH:18]=2)=[O:16])=[N:10]1.[CH3:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[CH:27]=[C:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([CH2:35][OH:36])=[CH:31][C:30]=3[F:37])[C:20]3[CH2:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=3[CH:18]=2)=[O:16])=[N:10]1
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참가 물질

6

반응물 3

HCID 674Dimethylamine2회HCID 5003444Sodium cyanoborohydride2회HCID 595600834-(2-fluoro-4-formyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

생성물 2

HCID 595600364-(4-dimethylaminomethyl-2-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid(1-methyl-1H-pyrazol-3-yl)-amide수율 24%
HCID 59560258
4-(2-Fluoro-4-hydroxymethyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide
수율 25%

시약·촉매·용매 1

HCID 887Methanol용매

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온도
50 °C

실험 절차

To dimethylamine (0.6 mL, 2.0 M, 1.0 mmol) in MeOH (5 mL) was added NaCNBH3 (31 mg, 0.49 mmol). The mixture was heated to 50° C. for 1 hr, and then 4-(2-fluoro-4-formyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid(1-methyl-1H-pyrazol-3-yl)-amide (39a) (100 mg, 0.24 mmol) was added. The reaction mixture was heated to 50° C. for 1 hr. Additional NaCNBH3 (31 mg, 0.49 mmol) and dimethylamine (0.3 mL, 2.0 M, 0.5 mmol) were added to the reaction mixture. The mixture was heated at 50° C. for 1 hr, then concentrated and purified by reverse phase chromatograph to give 4-(4-dimethylaminomethyl-2-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid(1-methyl-1H-pyrazol-3-yl)-amide (26 mg, 24% yield) and 4-(2-Fluoro-4-hydroxymethyl-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid(1-methyl-1H-pyrazol-3-yl)-amide (25 mg, 25% yield) as white solid.

후처리

  1. temperatureThe reaction mixture was heated to 50° C. for 1 hr
  2. temperatureThe mixture was heated at 50° C. for 1 hr
  3. concentrationconcentrated
  4. custompurified by reverse phase chromatograph

출처 및 근거

ORD 기록
ord-5b14fbf1bfd2425fa21d664b437c67a3
출처 데이터셋
uspto-grants-2012_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08119624B2

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