4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → n-(5-(1h-Pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-4-(morpholinomethyl)thiazol-2-amine

HRID 1684955

반응식

HRID 1684955 반응식
Br[C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[C:5]([NH:11][C:12]2[S:13][CH:14]=[C:15]([CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[N:16]=2)=[N:4][CH:3]=1.[NH:24]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[N:25]1.CC(C)([O-])C.[Na+]>CN(C=O)C.O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].[Pd].[Pd].[Pd]>[NH:24]1[CH:28]=[C:27]([C:2]2[N:7]3[N:8]=[CH:9][N:10]=[C:6]3[C:5]([NH:11][C:12]3[S:13][CH:14]=[C:15]([CH2:17][N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)[N:16]=3)=[N:4][CH:3]=2)[CH:26]=[N:25]1

참가 물질

7

반응물 3

HCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 23676156Sodium t-butoxideHCID 57541337N-(5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-4-(morpholinomethyl)thiazol-2-amine

생성물 1

HCID 135900093n-(5-(1h-Pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-4-(morpholinomethyl)thiazol-2-amine수율 29%

시약·촉매·용매 3

HCID 86600928Tetrakis palladium triphenylphosphine촉매HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
90 °C

실험 절차

The product of Step 1 (43 mg, 0.11 mmol), 4-pyrazole boronic acid pinacol ester (32 mg, 0.16 mmol), tetrakis palladium triphenylphosphine (13 mg, 0.11 mmol) and sodium tert-butoxide are suspended in a mixture of DMF (2 mL) and water (0.66 mL). The reaction is degassed with nitrogen for 10 min before being sealed and stirred at 90° C. for 16 h. The reaction is condensed in vacuo and the residue purified by column chromatography, eluting with 3% methanolic ammonia (7 N) in dichloromethane to give the title compound as a pale yellow powder (12 mg, 29%). 1H NMR (400 MHz, d6-DMSO) δ 2.48 (s, 4H, CH2CH2), 3.35 (s, 2H, CH2), 3.63 (t, 4H, J=6 Hz, CH2CH2), 6.97 (s, 1H, H), 8.43 (s, 1H, H), 8.61 (brs, 2H), 8.81 (s, 1H, H), 12.9-12.4 (brs, 2H, NH×2). MS (MH+, m/z) 384.

후처리

  1. customThe reaction is degassed with nitrogen for 10 min
  2. custombefore being sealed
  3. customcondensed in vacuo
  4. customthe residue purified by column chromatography
  5. washeluting with 3% methanolic ammonia (7 N) in dichloromethane

출처 및 근거

ORD 기록
ord-28dc4f014559453c819f8f85d20e4253
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08148369B2

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