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 1988445

反応式

HRID 1988445 の反応式
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

参加物

7

反応物 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

生成物 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-carboxylate収率 12.8%

試薬・触媒・溶媒 2

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

反応条件

温度
85 °C

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-00d4a838de3144fc9b4ecf191545514a
出典データセット
uspto-grants-2009_06
特許番号
US07553854B2

関連ノート

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