Tetrahydrofuran → HCID 59835147、化合物

HRID 271283

反応式

HRID 271283 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([NH2:28])[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.C1C[O:32][CH2:31]C1.[NH2:34][CH:35]1[CH2:39][CH2:38]C[CH:36]1[OH:40]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([NH:28][C:31]4[O:32][CH:39]5[CH2:38][O:40][CH2:36][CH:35]5[N:34]=4)[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

参加物

5

反応物 3

HCID 8028TetrahydrofuranHCID 143443NoName_4581HCID 53630477Allitinib metabolite M6

生成物 1

HCID 59835147HCID 59835147、化合物収率 65%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

N4-[3-Chloro-4-(3-fluorobenzyloxy)-phenyl]-N6-(3a,4,6,6a-tetrahydrofuro[3,4-d]oxazol-2-yl)-quinazoline-4,6-diamine is prepared by adding thioCDI (27 mg, 0.152 mmol) to a stirred solution of N4-[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-quinazoline-4,6-diamine (60 mg, 0.152 mmol) in 1:1 THF:DCM (8 mL). After 3 hours, 2-amino-cyclopentanol (30 mg, 0.30 mmol) is added and the reaction mixture stirred for 4 hours. Solvent is removed under reduced pressure and the resulting thiourea is triturated with diethyl ether. The crude thiourea is suspended in THF (10 mL) and 1 M NaOH in water (0.38 mL) is added followed by addition of a 1 M TsCl solution in THF (0.17 mL). After 1 hour, the reaction mixture is diluted with EtOAc and water, and the phases separated. The aqueous phase is extracted with EtOAc and the combined organic extracts are dried (Na2SO4) and concentrated. Purification by column chromatography (10:5:1 EtOAc:Hexanes:MeOH) provides the desired product (50 mg, 65%). MS APCI (+) m/z 506, 508 (M+1, Cl pattern) detected; 1H NMR (400 mHz, CD3CN) δ 8.49 (s, 1H), 8.23 (bs, 1H), 7.94 (s, 1H), 7.73 (m, 2H), 7.59 (m, 2H), 7.45 (m, 1H), 7.35 (d, 1H), 7.29 (d, 1H), 7.19-7.10 (m, 3H), 5.23 (s, 2H), 5.18 (m, 1H), 4.66 (m, 1H), 4.11 (d, 1H), 3.96 (d, 1H), 3.56 (dd, 2H).

後処理

  1. customN4-[3-Chloro-4-(3-fluorobenzyloxy)-phenyl]-N6-(3a,4,6,6a-tetrahydrofuro[3,4-d]oxazol-2-yl)-quinazoline-4,6-diamine is prepared
  2. customSolvent is removed under reduced pressure
  3. customthe resulting thiourea is triturated with diethyl ether
  4. addition1 M NaOH in water (0.38 mL) is added
  5. additionfollowed by addition of a 1 M TsCl solution in THF (0.17 mL)
  6. waitAfter 1 hour
  7. additionthe reaction mixture is diluted with EtOAc and water
  8. customthe phases separated
  9. extractionThe aqueous phase is extracted with EtOAc
  10. dry with materialthe combined organic extracts are dried (Na2SO4)
  11. concentrationconcentrated
  12. customPurification by column chromatography (10:5:1 EtOAc:Hexanes:MeOH)

出典と根拠

ORDレコード
ord-6d3e8ecc2cd54455ade5e131fece87ba
出典データセット
uspto-grants-2008_11
特許番号
US07452895B2

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