Sodium Carbonate → (S)-tert-butyl 3-(6-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzo[d]thiazol-2-ylamino)piperidine-1-carboxylate

HRID 1922242

반응식

HRID 1922242 반응식
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:31]=[CH:30][C:12]3[N:13]=[C:14]([NH:16][C@H:17]4[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18]4)[S:15][C:11]=3[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:32][N:33]1[CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:35]=[N:34]1.C([O-])([O-])=O.[Na+].[Na+].C([O-])(O)=O.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC>[CH3:32][N:33]1[CH:37]=[C:36]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:31]=[CH:30][C:12]4[N:13]=[C:14]([NH:16][C@H:17]5[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18]5)[S:15][C:11]=4[CH:10]=3)[CH:5]=[CH:4][N:3]=2)[CH:35]=[N:34]1

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 57725807(S)-tert-butyl 3-(6-(2-chloropyridin-4-yloxy)benzo[d]thiazol-2-ylamino)piperidine-1-carboxylate

생성물 1

HCID 57725561(S)-tert-butyl 3-(6-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzo[d]thiazol-2-ylamino)piperidine-1-carboxylate수율 12.8%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
85 °C

실험 절차

To the reaction mixture of (S)-tert-butyl 3-(6-(2-chloropyridin-4-yloxy)benzo[d]thiazol-2-ylamino)piperidine-1-carboxylate (68 mg, 148 μmol) in 1.2 m of DME, 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (40 mg, 192 μmol), Pd(dppf)2Cl2 (18 mg, 22 μmol) and aq. 2M Na2CO3 (400 μL, 800 μmol) were added. The reaction mixture was stirred at 85° C. for 72 hours or until done by LC. The reaction mixture was poured into 40 ml of saturated NaHCO3 solution and extracted with ethyl acetate (2×80 ml). The combined organic layers were washed with water (2×20 ml) and brine (20 ml), then dried over Na2SO4, filtered and evaporated in vacuo to give a brown glue (77 mg) that was purified on prep HPLC to give (S)-tert-butyl 3-(6-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzo[d]thiazol-2-ylamino)piperidine-1-carboxylate as powder (9.6 mg). ES/MS m/z 507.1 (MH+).

후처리

  1. additionwere added
  2. extractionextracted with ethyl acetate (2×80 ml)
  3. washThe combined organic layers were washed with water (2×20 ml) and brine (20 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto give a brown glue (77 mg) that
  8. customwas purified on prep HPLC

출처 및 근거

ORD 기록
ord-60ecd419fe864147ad54957eff233c2e
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08173689B2

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