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1-Hydroxybenzotriazole → Tak-778

HRID 987402
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인쇄 미리보기

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HRID 987402 반응식
Cl.C(N=C=NCCCN(C)C)C.[CH3:13][C@@H:14]1[S:20][C@@H:19]([C:21]([OH:23])=O)[CH2:18][C:17]2[CH:24]=[C:25]3[O:30][CH2:29][O:28][C:26]3=[CH:27][C:16]=2[C:15]1=[O:31].[NH2:32][C:33]1[CH:47]=[CH:46][C:36]([CH2:37][P:38](=[O:45])([O:42][CH2:43][CH3:44])[O:39][CH2:40][CH3:41])=[CH:35][CH:34]=1.ON1C2C=CC=CC=2N=N1>ClCCl.CN(C)C=O.O>[CH2:43]([O:42][P:38]([CH2:37][C:36]1[CH:35]=[CH:34][C:33]([NH:32][C:21]([C@H:19]2[CH2:18][C:17]3[CH:24]=[C:25]4[O:30][CH2:29][O:28][C:26]4=[CH:27][C:16]=3[C:15](=[O:31])[C@H:14]([CH3:13])[S:20]2)=[O:23])=[CH:47][CH:46]=1)([O:39][CH2:40][CH3:41])=[O:45])[CH3:44]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 88358Diethyl p-aminobenzylphosphonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9845635(+/-)-trans-1,2,4,5-Tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid

생성물 1

HCID 9806177Tak-778수율 44%

시약·촉매·용매

3
HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
25 °C

실험 절차

A solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.39 g) in dichloromethane (7 ml) was added to a solution of (2R,4S)-(−)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid (0.47 g) and diethyl 4-aminobenzylphosphonate (0.41 g) in N,N-dimethylformamide (DMF) (7 ml) at 0° C., followed by the addition of 1-hydroxybenzo-triazole (HOBt) (0.28 g). This mixture was stirred at 0° C. for 1 hour and at room temperature (25° C.) for 15 hours, after which it was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried (using MgSO4), after which the solvent was distilled off; the residual crystals were collected by filtration, followed by recrystallization from ethyl acetate-hexane and then recrystalized from methanol-hexane to yield (2R,4S)-(−)-N-[4-(diethoxyphosphorylmethyl)phenyl]-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzo-thiepin-2-carboxamide (0.37 g, 44%). Colorless Prisms.

후처리

  1. extractionextracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with water
  3. dry with materialdried (using MgSO4)
  4. distillationafter which the solvent was distilled off
  5. filtrationthe residual crystals were collected by filtration
  6. customfollowed by recrystallization from ethyl acetate-hexane
  7. customrecrystalized from methanol-hexane

출처 및 근거

ORD 기록
ord-6788f39be1a34de8b3b1aa6fe9188b28
출처 데이터셋
uspto-grants-2003_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06632807B1

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