Ozone → N-(2,2-Difluoro-3-morpholin-4-yl-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamide

HRID 6885

反応式

HRID 6885 の反応式
[O:1]1[CH:5]=[CH:4][CH2:3][CH2:2]1.O=[O+][O-].[NH2:9][CH2:10][C:11]([F:38])([F:37])[CH2:12][NH:13][C:14](=[O:36])[C:15]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]([NH:22][CH2:23][C:24]2[S:28][C:27]([NH:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)=[N:26][CH:25]=2)[CH:16]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CO.C(Cl)Cl>[F:38][C:11]([F:37])([CH2:10][N:9]1[CH2:4][CH2:5][O:1][CH2:2][CH2:3]1)[CH2:12][NH:13][C:14](=[O:36])[C:15]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]([NH:22][CH2:23][C:24]2[S:28][C:27]([NH:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)=[N:26][CH:25]=2)[CH:16]=1

参加物

7

反応物 4

HCID 24823OzoneHCID 709342,3-DihydrofuranHCID 5049666Sodium triacetoxyborohydrideHCID 22019140N-(3-Amino-2,2-difluoro-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamide

生成物 1

HCID 22019082N-(2,2-Difluoro-3-morpholin-4-yl-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamide収率 51.2%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

A solution of dihydrofuran (35 mg, 0.5 mmol) in MeOH (1.5 mL) was treated with ozone at −78° C. until the solution turned blue. Argon was streamed through the solution to remove excess ozone. The solution was warmed to 0° C., and N-(3-Amino-2,2-difluoro-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamide (Example 107) (12 mg, 0.027 mmol)) followed by NaBH(OAc)3 (84 mg) were added over a period of 3 h. The mixture was diluted with CH2Cl2, washed with sat. NaHCO3, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography [silica gel, 1% (NH3/MeOH(2M) in EtOAc] to afford the title compound (7 mg, 51%) as a white solid. LC/MS; (M+H)+=507. 1HNMR (CD3OD): δ 2.47 (m, 4H); 2.66 (t, 2H, J=13.7 Hz); 3.53 (m, 4H); 3.80 (t, 2H, J=14.3 Hz); 4.48 (s, 2H); 6.78 (m, 1H); 6.86 (d, 1H, J=8.25 Hz); 7.0 (m, 2H); 7.15 (s, 1H); 7.23 (m, 1H); 7.54 (m, 1H), 8.15 (d, 1H, J=4.4 Hz).

後処理

  1. customto remove excess ozone
  2. additionwere added over a period of 3 h
  3. washwashed with sat. NaHCO3
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography [silica gel, 1% (NH3/MeOH(2M) in EtOAc]

出典と根拠

ORDレコード
ord-15517eb9e2224d3691c2bd14be7ee22b
出典データセット
uspto-grants-2006_08
特許番号
US07084160B2

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