Diisopropylethylamine → N-(4,4-difluorocyclohexyl)-8-nitroquinazolin-4-amine

HRID 1469729

반응식

HRID 1469729 반응식
Cl[C:2]1[C:11]2[C:6](=[C:7]([N+:12]([O-:14])=[O:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:15][C:16]1([F:23])[CH2:21][CH2:20][CH:19]([NH2:22])[CH2:18][CH2:17]1.CCN(C(C)C)C(C)C>CC(O)C>[F:15][C:16]1([F:23])[CH2:21][CH2:20][CH:19]([NH:22][C:2]2[C:11]3[C:6](=[C:7]([N+:12]([O-:14])=[O:13])[CH:8]=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)[CH2:18][CH2:17]1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 3847030(4,4-Difluorocyclohexyl)amineHCID 114584714-Chloro-8-nitroquinazoline

생성물 1

HCID 71678050N-(4,4-difluorocyclohexyl)-8-nitroquinazolin-4-amine수율 61.2%

시약·촉매·용매 1

HCID 3776Isopropanol용매

실험 절차

A solution of 4-chloro-8-nitroquinazoline (Intermediate-7, step 2, 200 mg, 0.954 mmol), 4,4-difluorocyclohexanamine (491 mg, 2.86 mmol) and DIPEA (367 mg, 2.86 mmol) in iPrOH (2 mL) was heated in a sealed tube at 80° C. for 2 h. Then the reaction mixture was quenched with water at rt and was extracted with CHCl3. The organic layer was separated, dried, filtered and concentrated. The concentrate was purified by column chromatography using 3-5% EtOAc in CHCl3 to afford 180 mg of the title product. 1H NMR (300 MHz, DMSO d6): δ 8.59-8.55 (m, 2H), 8.43-8.40 (d, J=7.2 Hz, 1H), 8.27-8.25 (d, J=7.8 Hz, 1H), 7.69-7.63 (t, J=7.8 Hz, 1H), 4.41 (m, 1H), 2.26-2.00 (m, 6H), 1.75-1.71 (m, 2H); MS (m/z): 309.18 (M+H)+.

후처리

  1. customThen the reaction mixture was quenched with water at rt
  2. extractionwas extracted with CHCl3
  3. customThe organic layer was separated
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe concentrate was purified by column chromatography

출처 및 근거

ORD 기록
ord-0921096d044e42d59ec9c1b94892f827
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09006257B2

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