Cesium carbonate → (3aR,7aR)-2,2-dimethyl-3-(6-((5-(2-morpholinoethoxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)octahydrobenzo[d]oxazole

HRID 1848210노트

반응식

HRID 1848210 반응식
[CH3:1][C:2]1([CH3:31])[N:6]([C:7]2[S:8][C:9]3[CH:15]=[C:14]([CH2:16][N:17]4[C:21]5[CH:22]=[CH:23][C:24]([OH:26])=[CH:25][C:20]=5[N:19]=[CH:18]4)[CH:13]=[CH:12][C:10]=3[N:11]=2)[C@@H:5]2[CH2:27][CH2:28][CH2:29][CH2:30][C@H:4]2[O:3]1.I[CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.C([O-])([O-])=O.[Cs+].[Cs+].CN1C(=O)CCC1>CCOC(C)=O>[CH3:1][C:2]1([CH3:31])[N:6]([C:7]2[S:8][C:9]3[CH:15]=[C:14]([CH2:16][N:17]4[C:21]5[CH:22]=[CH:23][C:24]([O:26][CH2:33][CH2:34][N:35]6[CH2:40][CH2:39][O:38][CH2:37][CH2:36]6)=[CH:25][C:20]=5[N:19]=[CH:18]4)[CH:13]=[CH:12][C:10]=3[N:11]=2)[C@@H:5]2[CH2:27][CH2:28][CH2:29][CH2:30][C@H:4]2[O:3]1

참가 물질

6

반응물 4

HCID 10796Cesium carbonateHCID 13387N-methyl-2-pyrrolidoneHCID 111491684-(2-iodoethyl)morpholineHCID 866811861-((2-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazol-6-yl)methyl)-1H-benzo[d]imidazol-5-ol

생성물 1

HCID 86681185(3aR,7aR)-2,2-dimethyl-3-(6-((5-(2-morpholinoethoxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)octahydrobenzo[d]oxazole수율 67%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 1-((2-((3aR,7aR)-2,2-dimethylhexahydrobenzo[d]oxazol-3(2H)-yl)benzo[d]thiazol-6-yl)methyl)-1H-benzo[d]imidazol-5-ol (100 mg, 0.23 mmol) from Step 1 of this Example, 4-(2-iodoethyl)morpholine (111 mg, 0.46 mmol) from Step 2 of this Example, Cs2CO3 (250 mg, 0.69 mmol), and NMP (2 mL) was stirred at rt for 3 h. The mixture was diluted with EtOAc and washed with brine. The organic layer was separated, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography, eluting with a gradient of 33% DCM in THF to 100% THF, to afford (3aR,7aR)-2,2-dimethyl-3-(6-((5-(2-morpholinoethoxy)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)octahydrobenzo[d]oxazole (84 mg, 67%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.90 (s, 1H), 7.58 (d, J=8.1 Hz, 1H), 7.40 (s, 1H), 7.29 (s, 1H), 7.14-7.19 (m, 2H), 6.90 (m, 1H), 5.35 (s, 2H), 4.11-4.17 (m, 2H), 3.70-3.75 (m, 4H), 3.65 (m, 1H), 3.08 (m, 1H), 2.76-2.84 (m, 3H), 2.57-2.60 (m, 4H), 2.17 (m, 1H), 1.82-1.92 (m, 2H), 1.78 (s, 3H), 1.46 (s, 3H), 1.33-1.39 (m, 4H); LCMS (ESI) m/z 548 (M+H)+.

후처리

  1. washwashed with brine
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel flash chromatography
  7. washeluting with a gradient of 33% DCM in THF to 100% THF

출처 및 근거

ORD 기록
ord-a40711cf668e45eaa9a41616b783cfd2
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08952058B2

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