Diisopropylethylamine → (4-Benzyloxyphenyl)-(6-(5-(1,3-dioxolan-2-yl)-furan-2-yl)-7-fluoro-quinazolin-4-yl)-amine

HRID 51116노트

반응식

HRID 51116 반응식
Cl.[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([F:28])=[C:24](I)[CH:25]=3)[N:20]=[CH:19][N:18]=2)=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[O:29]1[CH2:33][CH2:32][O:31][CH:30]1[C:34]1[O:38][C:37]([Sn](CCCC)(CCCC)CCCC)=[CH:36][CH:35]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([F:28])=[C:24]([C:37]4[O:38][C:34]([CH:30]5[O:31][CH2:32][CH2:33][O:29]5)=[CH:35][CH:36]=4)[CH:25]=3)[N:20]=[CH:19][N:18]=2)=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 10960952Stannane, tributyl[5-(1,3-dioxolan-2-yl)-2-furanyl]-HCID 21952109(4-Benzyloxyphenyl)-(6-iodo-7-fluoroquinazolin-4-yl)-amine hydrochloride

생성물 1

HCID 21951946(4-Benzyloxyphenyl)-(6-(5-(1,3-dioxolan-2-yl)-furan-2-yl)-7-fluoro-quinazolin-4-yl)-amine수율 59.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

Synthesized according to Procedure B from a solution of (4-benzyloxyphenyl)-(6-iodo-7-fluoro-quinazolin-4-yl)-amine hydrochloride (508 mg, 1 mmole), 5-(1,3-dioxolan-2-yl)-2-(tributylstannyl)furan (645 mg, 1.5 mmole), diisopropylethyl amine (650 mg, 5 mmole), and dichlorobis(triphenylphosphine) palladium (140 mg, 0.2 mmole) in 6 ml of DMF under nitrogen was stirred at 100° C. (oil bath temperature) for 4 hours. The cooled reaction mixture was extracted with water (100 ml) and ethyl acetate (100 ml). The organic phase was washed with brine (100 ml). The aqueous layers were combined and washed with additional ethyl acetate (100 ml). The organic layers were combined, dried with MgSO4, filtered and concentrated to a residue. The residue was chromatographed on silica gel with a methanol-chloroform mixture. Fractions were collected, combined, and concentrated. The resultant solid was suspended in dichloromethane (10 ml) and diethyl ether was added facilitate precipitation. The solid was filtered and dried under vacuum at room temperature to yield a yellowish solid 287 mg (59%). 1H NMR (400 MHz, DMSO-d6) δ: 10.1(s, 1H), 8.85(d, 1H), 8.45(s, 1H), 7.6(m, 3H), 7.44(d, 2H), 7.38(m, 2H), 7.31 (m, 1H), 7.03(m, 2H), 6.94(m, 1H), 6.74(d, 1H), 6.01(s, 1H), 5.1(s, 2H), 4.10(m, 2H), 3.96(m, 2H). ESI-MS m/z 482(M−1).

후처리

  1. customSynthesized
  2. customThe cooled reaction mixture
  3. extractionwas extracted with water (100 ml) and ethyl acetate (100 ml)
  4. washThe organic phase was washed with brine (100 ml)
  5. washwashed with additional ethyl acetate (100 ml)
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to a residue
  9. customThe residue was chromatographed on silica gel with a methanol-chloroform mixture
  10. customFractions were collected
  11. concentrationconcentrated
  12. additiondiethyl ether was added
  13. customprecipitation
  14. filtrationThe solid was filtered
  15. customdried under vacuum at room temperature

출처 및 근거

ORD 기록
ord-40fd6742587d4b309843b2a6274c8c9a
출처 데이터셋
uspto-grants-2004_03
특허 번호
US06713485B2

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