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 1748204ノート

反応式

HRID 1748204 の反応式
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

参加物

7

反応物 3

HCID 81531DiisopropylethylamineHCID 67981000Methyl 2-chloro-4-methoxybenzo[d]thiazole-6-carboxylateHCID 67983256HCID 67983256、化合物

生成物 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-carboxylate収率 53.3%

試薬・触媒・溶媒 3

HCID 8857Ethyl Acetate溶媒HCID 31374Dimethylacetamide溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
120 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-73649a9275c34657b9e832229d2aaf32
出典データセット
uspto-grants-2015_10
特許番号
US09150568B2

反応ノート

読み込み中…