Lithium Chloride → (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(5-methyl-6-(1-methyl-1H-indazol-5-yl)pyridin-2-yl)benzo[d]thiazol-6-yl)acetate

HRID 879561노트

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HRID 879561 반응식
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH3:17])[N:12]=[CH:11]3)[C:5]([CH3:18])=[CH:4][CH:3]=1.[Li+].[Cl-].Br[C:22]1[S:23][C:24]2[C:30]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=3)=[C:29]([C@H:38]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[C:39]([O:41][CH2:42][CH3:43])=[O:40])[C:28]([CH3:49])=[CH:27][C:25]=2[N:26]=1>O1CCOCC1.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:45]([O:44][C@@H:38]([C:29]1[C:28]([CH3:49])=[CH:27][C:25]2[N:26]=[C:22]([C:2]3[CH:3]=[CH:4][C:5]([CH3:18])=[C:6]([C:8]4[CH:9]=[C:10]5[C:14](=[CH:15][CH:16]=4)[N:13]([CH3:17])[N:12]=[CH:11]5)[N:7]=3)[S:23][C:24]=2[C:30]=1[C:31]1[CH:32]=[CH:33][C:34]([Cl:37])=[CH:35][CH:36]=1)[C:39]([O:41][CH2:42][CH3:43])=[O:40])([CH3:46])([CH3:47])[CH3:48]

참가 물질

8

반응물 3

HCID 433294Lithium ChlorideHCID 86700141(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetateHCID 867003845-(6-chloro-3-methylpyridin-2-yl)-1-methyl-1H-indazole

생성물 1

HCID 86700385(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(5-methyl-6-(1-methyl-1H-indazol-5-yl)pyridin-2-yl)benzo[d]thiazol-6-yl)acetate

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 178418476HCID 178418476, 화합물촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매2회

반응 조건

온도
90 °C

실험 절차

In a 10 mL reaction vial, 5-(6-chloro-3-methylpyridin-2-yl)-1-methyl-1H-indazole (100 mg, 0.389 mmol) was dissolved in dioxane (5 mL) at rt. The solution was bubbled with argon for 5 min. Then Sn2(n-Bu)6 (0.253 mL, 0.508 mmol), LiCl (100 mg, 2.38 mmol), Pd(PPh3)2Cl2 (27 mg, 0.039 mmol) and Pd(PPh3)4 (45 mg, 0.039 mmol) were added sequentially. The resulting reaction mixture was sealed and heated to 90° C. in oil bath. To this mixture, a solution of (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (289 mg, 0.583 mmol) in dioxane (5 mL) was added slowly through syringe pump over 1.5 h. The resulting reaction mixture was stirred at 100° C. in oil bath for 16 h. The reaction was then diluted with EtOAc (20 mL) and filtered to remove solid. The filtrate was concentrated and purified on silica gel column with 0-20% EtOAc/Hex to afford product as. LCMS-ESI+: calc'd for: C36H35ClN4O3S: 639.2, 640.2, 641.2 (M+H+); found: 639.1, 640.1, 641.1 (M+H+).

후처리

  1. customIn a 10 mL reaction vial
  2. customThe solution was bubbled with argon for 5 min
  3. customThe resulting reaction mixture
  4. customwas sealed
  5. customThe resulting reaction mixture
  6. filtrationfiltered
  7. customto remove solid
  8. concentrationThe filtrate was concentrated
  9. custompurified on silica gel column with 0-20% EtOAc/Hex
  10. customto afford product as

출처 및 근거

ORD 기록
ord-2023eaffc3b74d988eb1a387fd66f69f
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987250B2

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