Acetic Acid → HCID 178481014, 화합물

HRID 897452노트

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HRID 897452 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]3[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]3)[N:9]=[C:10]([I:11])[C:3]=12.[CH3:19][N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[I:11][C:10]1[C:3]2[C:4](=[N:5][CH:6]=[N:7][C:2]=2[NH2:1])[N:8]([C@H:12]2[CH2:17][CH2:16][C@@H:15]([N:23]3[CH2:24][CH2:25][N:20]([CH3:19])[CH2:21][CH2:22]3)[CH2:14][CH2:13]2)[N:9]=1

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydride2회HCID 223467294-(4-Amino-3-iodo-1h-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexanone

생성물 1

HCID 178481014HCID 178481014, 화합물수율 56.8%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

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온도
40 °C

실험 절차

A mixture of 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-cyclohexanone (Intermediate AK) (1.32 g, 0.0037 mol), N-methylpiperazine (1.11 g, 0.011 mol) and acetic acid (0.66 g, 0.011 mol) in 1,2-dichloroethane (50 mL) was stirred for 10 min at 40° C. and sodium triacetoxyborohydride (1.09 g, 0.0052 mol) was added at once. The mixture was stirred at ambient temperature under an atmosphere of nitrogen for 24 hours and sodium triacetoxyborohydride (0.25 g, 0.0012 mol) was added. The mixture was stirred for another 48 hours , the solvent removed under reduced pressure and the residue partitioned between saturated aqueous sodium bicarbonate solution (80 mL) and chloroform (50 mL). The organic layer was separated and the aqueous layer further extracted with chloroform (3×50 mL). The combined organic extracts were dried over magnesium sulfate and the solvent removed under reduced pressure to yield a yellow oil. The compound was further purified by flash chromatography on silica gel using dichloromethane/triethylamine/methanol (88:11:1) as a mobile phase to yield cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (0.93 g, 0.0021 mol): 1H NMR (DMSO-d6, 400 MHz) 8.18 (s, 1H), 4.71 (m, 1H), 2.38-1.9 (m, 13H), 2.17 (s, 3H), 1.63-1.5 (m, 4H); TLC (dichloromethane/triethylamine=9:1) Rf 0.24 and trans-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (0.38 g, 0.00086 mol): 1H NMR (DMSO-d6, 400 MHz) 8.18 (s, 1H), 4.55 (m, 1H), 2.38-1.9 (m, 15H), 2.15 (s, 3H), 1.42 (m, 2H); TLC (dichloromethane/triethylamine=9:1) Rf 0.11.

후처리

  1. stirringThe mixture was stirred at ambient temperature under an atmosphere of nitrogen for 24 hours
  2. stirringThe mixture was stirred for another 48 hours
  3. customthe solvent removed under reduced pressure
  4. customthe residue partitioned between saturated aqueous sodium bicarbonate solution (80 mL) and chloroform (50 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer further extracted with chloroform (3×50 mL)
  7. dry with materialThe combined organic extracts were dried over magnesium sulfate
  8. customthe solvent removed under reduced pressure
  9. customto yield a yellow oil
  10. customThe compound was further purified by flash chromatography on silica gel

출처 및 근거

ORD 기록
ord-47888edd099044aabe7436cbd8022b19
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06921763B2

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