Diisopropylethylamine → Methyl 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-methoxybenzo[d]thiazole-6-carboxylate

HRID 1748204노트

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HRID 1748204 반응식
Cl[C:2]1[S:3][C:4]2[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:8]=[C:7]([O:15][CH3:16])[C:5]=2[N:6]=1.[CH:17]12[NH:24][CH:21]([CH2:22][CH2:23]1)[CH2:20][CH:19]([O:25][CH2:26][C:27]1[C:28]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[O:41][C:42]([F:45])([F:44])[F:43])=[N:29][O:30][C:31]=1[CH:32]1[CH2:34][CH2:33]1)[CH2:18]2.C(N(C(C)C)CC)(C)C>CC(N(C)C)=O.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[CH:32]1([C:31]2[O:30][N:29]=[C:28]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[O:41][C:42]([F:43])([F:44])[F:45])[C:27]=2[CH2:26][O:25][CH:19]2[CH2:18][CH:17]3[N:24]([C:2]4[S:3][C:4]5[CH:10]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:8]=[C:7]([O:15][CH3:16])[C:5]=5[N:6]=4)[CH:21]([CH2:22][CH2:23]3)[CH2:20]2)[CH2:33][CH2:34]1

참가 물질

7

반응물 3

HCID 81531DiisopropylethylamineHCID 67981000Methyl 2-chloro-4-methoxybenzo[d]thiazole-6-carboxylateHCID 67983256HCID 67983256, 화합물

생성물 1

HCID 59053602Methyl 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)-4-methoxybenzo[d]thiazole-6-carboxylate수율 53.3%

시약·촉매·용매 3

HCID 8857Ethyl Acetate용매HCID 31374Dimethylacetamide용매HCID 516892Sodium Bicarbonate용매

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온도
120 °C

실험 절차

The ester, methyl 2-chloro-4-methoxybenzo[d]thiazole-6-carboxylate (124 mg, 0.48 mmol) and 4-((8-azabicyclo[3.2.1]octan-3-yloxy)methyl)-5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole (200 mg, 0.48 mmol) and diisopropylethylamine (0.1 mL, 0.7 mmol) were sequentially dissolved in dimethylacetamide (1 mL) and heated to 120° C. overnight. The reaction mixture was allowed to cool to room temperature and then diluted with ethyl acetate and aqueous saturated sodium bicarbonate solution. The organics were separated, the aqueous layer was subjected to a further wash with ethyl acetate, and the organics were combined and dried (MgSO4) then evaporated in vacuo. The product was purified by silica gel chromatography with a gradient of 0-100% ethyl acetate/hexanes to furnish 161 mg of a clear oil that was used directly in the following transformation without further manipulation.

후처리

  1. temperatureto cool to room temperature
  2. customThe organics were separated
  3. washa further wash with ethyl acetate
  4. dry with materialdried (MgSO4)
  5. customthen evaporated in vacuo
  6. customThe product was purified by silica gel chromatography with a gradient of 0-100% ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-73649a9275c34657b9e832229d2aaf32
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09150568B2

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