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Trimethyl orthoformate → Methyl (3-amino-4-fluoro-5-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate

HRID 921749
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HRID 921749 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([N:15]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[C:16](=[O:19])[O:17][CH3:18])[CH:5]=[C:6]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[C:7]=1[F:8].[O:29]1[CH2:32][C:31](=O)[CH2:30]1.C(OC)(OC)OC.C([O-])(=O)C.[K+].C([BH3-])#N.[Na+]>CO.O1CCCC1>[NH2:1][C:2]1[CH:3]=[C:4]([N:15]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=2)[C:16](=[O:19])[O:17][CH3:18])[CH:5]=[C:6]([N:9]2[CH2:10][CH2:11][N:12]([CH:31]3[CH2:32][O:29][CH2:30]3)[CH2:13][CH2:14]2)[C:7]=1[F:8]
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참가 물질

8

반응물 5

HCID 9005Trimethyl orthoformateHCID 517044Potassium AcetateHCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 86708631Methyl (3-amino-4-fluoro-5-(piperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate

생성물 1

HCID 86708633Methyl (3-amino-4-fluoro-5-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate
수율 92.4%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

methyl (3-amino-4-fluoro-5-(piperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate (470 mg, 0.605 mmol) (crude product from above, contains DCE and TFA) was dissolved in methanol (5 ml)+Tetrahydrofuran (5 ml). oxetan-3-one (0.15 ml, 2.56 mmol), Trimethyl orthoformate (1 ml, 9.05 mmol) and potassium acetate (119 mg, 1.210 mmol) were added and the mixture stirred at room temperature for 15 minutes. pH was checked to be ˜4.5. Sodium cyanoborohydride (160 mg, 2.55 mmol) was added and stirring at room temperature continued for 20 hours. The reaction mixture was partitioned between EtOAc and dilutes aq. NaHCO3 solution. The organic layer was washed with brine, then dried over MgSO4 and evaporated to dryness to give crude methyl (3-amino-4-fluoro-5-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate (248.4 mg) which was used without further purification.

후처리

  1. stirringstirring at room temperature
  2. waitcontinued for 20 hours
  3. customThe reaction mixture was partitioned between EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. customevaporated to dryness

출처 및 근거

ORD 기록
ord-7e975669969240d7be4c99969357e044
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09273057B2

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