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Diisopropylethylamine → Isobutyl 3-(5-((1R,2S)-1-(4H-benzo[d][1,3]dioxin-7-yl)-2-(2,2-difluoropropanamido)propoxy)-1H-indazol-1-yl)benzoate

HRID 1510603
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HRID 1510603 반응식
[NH2:1][C@@H:2]([CH3:37])[C@@H:3]([C:27]1[CH:28]=[CH:29][C:30]2[CH2:35][O:34][CH2:33][O:32][C:31]=2[CH:36]=1)[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:15]=[C:16]([CH:24]=[CH:25][CH:26]=1)[C:17]([O:19][CH2:20][CH:21]([CH3:23])[CH3:22])=[O:18])[N:9]=[CH:8]2.[F:38][C:39]([F:44])([CH3:43])[C:40](O)=[O:41].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C>ClCCl.O>[O:32]1[C:31]2[CH:36]=[C:27]([C@@H:3]([O:4][C:5]3[CH:6]=[C:7]4[C:11](=[CH:12][CH:13]=3)[N:10]([C:14]3[CH:15]=[C:16]([CH:24]=[CH:25][CH:26]=3)[C:17]([O:19][CH2:20][CH:21]([CH3:22])[CH3:23])=[O:18])[N:9]=[CH:8]4)[C@@H:2]([NH:1][C:40](=[O:41])[C:39]([F:44])([F:38])[CH3:43])[CH3:37])[CH:28]=[CH:29][C:30]=2[CH2:35][O:34][CH2:33]1
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참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27828252,2-Difluoropropionic acidHCID 59272925HCID 59272925, 화합물

생성물 1

HCID 59272926Isobutyl 3-(5-((1R,2S)-1-(4H-benzo[d][1,3]dioxin-7-yl)-2-(2,2-difluoropropanamido)propoxy)-1H-indazol-1-yl)benzoate
수율 80.2%

시약·촉매·용매 2

HCID 962Water용매2회HCID 6344Dichloromethane용매2회

실험 절차

A mixture of isobutyl 3-(5-((1R,2S)-2-amino-1-(4H-benzo[d][1,3]dioxin-7-yl)propoxy)-1H-indazol-1-yl)benzoate (420 mg, 0.84 mmol) (I5b), 2,2-difluoropropanoic acid (213 mg, 1.94 mmol) and HBTU (420 mg, 1.11 mmol) were suspended in dichloromethane (10 mL). N-ethyl-N-isopropylpropan-2-amine (0.85 mL, 5.13 mmol) was added and the mixture was stirred at room temperature overnight. Water (ca 10 mL) was added to the solution. After stirring for some minutes the mixture was added to a phase separator. The water phase was stirred with dichloromethane (5 mL) and added to the phase separator. The combined organic phases were concentrated to a brown oil. Purification by flash chromatography on silica (dichloromethane/ethyl acetate 10/1) gave the title compound as a white foam (400 mg, 80%).

후처리

  1. stirringAfter stirring for some minutes the mixture
  2. additionwas added to a phase separator
  3. additionadded to the phase separator
  4. concentrationThe combined organic phases were concentrated to a brown oil
  5. customPurification by flash chromatography on silica (dichloromethane/ethyl acetate 10/1)

출처 및 근거

ORD 기록
ord-9eb39617a83249d3ac14d9382c9a8e17
출처 데이터셋
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08211930B2

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