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Phosphorus oxychloride → N-cyclobutyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzamide

HRID 2354165
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HRID 2354165 반응식
P(Cl)(Cl)(Cl)=O.[CH3:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][C:8]=1[N:16]1[C:25](=[O:26])[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([N:27]3[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]3)[CH:23]=2)[N:18]=[CH:17]1.[CH:34]1([NH2:38])[CH2:37][CH2:36][CH2:35]1>N1C=CC=CC=1>[CH:34]1([NH:38][C:11](=[O:13])[C:10]2[CH:14]=[CH:15][C:7]([CH3:6])=[C:8]([N:16]3[C:25](=[O:26])[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([N:27]5[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]5)[CH:23]=4)[N:18]=[CH:17]3)[CH:9]=2)[CH2:37][CH2:36][CH2:35]1
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참가 물질

5

반응물 3

HCID 24813Phosphorus oxychlorideHCID 75645CyclobutylamineHCID 669188194-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid

생성물 1

HCID 11224214N-cyclobutyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzamide

시약·촉매·용매 1

HCID 1049Pyridine용매

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온도
120 °C

실험 절차

Phosphorus oxychloride (0.08 ml) was added to a mixture of 4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid (0.30 g), cyclobutylamine (0.09 ml) and pyridine (5 ml) and the resultant was heated to 120° C. for 5 minutes in a microwave (Personal Chemistry Emrys Optimizer with 300 W magnetron). The mixture was evaporated. The residue was partitioned between ethyl acetate and saturated NaHCO3 solution. The organic phase was dried (magnesium sulphate) and evaporated and the residue purified by column chromatography on a silica column using initially methylene chloride and then a 9:1 mixture of methylene chloride and methanol as eluent. There was thus obtained the title compound (0.16 g); NMR Spectrum: (DMSOd6) 1.68 (m, 2H), 2.05 (m, 2H), 2.14 (s, 3H), 2.20 (m, 2H), 2.24 (s, 3H), 2.48 (m, 4H), 3.29 (m, 4H), 4.42 (m, 1H), 7.49 (d, 1H), 7.53 (d, 1H), 7.65 (m, 2H), 7.87 (d, 1H), 7.92 (m, 1H), 8.10 (s, 1H), 8.60 (d, 1H); Mass Spectrum: M+H+ 432.

후처리

  1. customThe mixture was evaporated
  2. customThe residue was partitioned between ethyl acetate and saturated NaHCO3 solution
  3. dry with materialThe organic phase was dried (magnesium sulphate)
  4. customevaporated
  5. customthe residue purified by column chromatography on a silica column
  6. additiona 9:1 mixture of methylene chloride and methanol as eluent

출처 및 근거

ORD 기록
ord-e0f6d652b5f146a0b079ef603153bb40
출처 데이터셋
uspto-grants-2010_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07750154B2

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