Dichloromethane → 4-[3-methyl-7-(2-methyl-1,3-thiazol-4-yl)-3,4-dihydroisoquinolin-2(1H)-yl]-6-(4-methylpiperazin-1-yl) pyrimidin-2-amine

HRID 2090452노트

반응식

HRID 2090452 반응식
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[C:12]([N:14]3[CH:23]([CH3:24])[CH2:22][C:21]4[C:16](=[CH:17][C:18](B5OC(C)(C)C(C)(C)O5)=[CH:19][CH:20]=4)[CH2:15]3)[N:11]=[C:10]([NH2:34])[N:9]=2)[CH2:4][CH2:3]1.Br[C:36]1[N:37]=[C:38]([CH3:41])[S:39][CH:40]=1.C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.O>[CH3:24][CH:23]1[CH2:22][C:21]2[C:16](=[CH:17][C:18]([C:36]3[N:37]=[C:38]([CH3:41])[S:39][CH:40]=3)=[CH:19][CH:20]=2)[CH2:15][N:14]1[C:12]1[CH:13]=[C:8]([N:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)[N:9]=[C:10]([NH2:34])[N:11]=1

참가 물질

7

반응물 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27631864-Bromo-2-methyl-1,3-thiazoleHCID 594022564-(4-methylpiperazin-1-yl)-6-[3-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl]pyrimidin-2-amine

생성물 1

HCID 467019184-[3-methyl-7-(2-methyl-1,3-thiazol-4-yl)-3,4-dihydroisoquinolin-2(1H)-yl]-6-(4-methylpiperazin-1-yl) pyrimidin-2-amine

시약·촉매·용매 2

HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

A mixture of 4-(4-methylpiperazin-1-yl)-6-[3-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl]pyrimidin-2-amine (0.0464 g, 0.100 mmol), 4-bromo-2-methyl-1,3-thiazole (0.0231 g, 0.130 mmol, Frontier, Cat. No. B4559) in 1,4-dioxane (1.0 mL) was stirred at r.t. for 10 min. Potassium carbonate (63.0 mg, 0.456 mmol) in water (0.50 mL) was added to give a deep red solution. The mixture was degassed and refilled with nitrogen three times. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (5.0 mg, 0.0061 mmol) was added and the mixture was degassed and refilled with nitrogen three times and then heated at 120° C.) (oil bath temperature) for 3 h. After cooling, the mixture was diluted with methanol, and filtered. The filtrate was purified on RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+: m/z=436.1.

후처리

  1. customto give a deep red solution
  2. customThe mixture was degassed
  3. additionrefilled with nitrogen three times
  4. customthe mixture was degassed
  5. additionrefilled with nitrogen three times
  6. temperatureAfter cooling
  7. additionthe mixture was diluted with methanol
  8. filtrationfiltered
  9. customThe filtrate was purified on RP-HPLC (pH=10)

출처 및 근거

ORD 기록
ord-78395596a7344c71ad6a6d56089072f7
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08436008B2

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