Chloroform → 5-Amino-5-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]azepan-2-one

HRID 410715ノート

反応式

HRID 410715 の反応式
CC(S([NH:7][C:8]1([C:18]2[S:19][C:20]([C:23]3[CH:28]=[C:27]([NH:29][C:30]4[N:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][N:31]=4)[CH:26]=[C:25]([CH3:40])[CH:24]=3)=[CH:21][N:22]=2)[CH2:17][CH2:16][C:11]2(OCC[O:12]2)[CH2:10][CH2:9]1)=O)(C)C.C(Cl)(Cl)Cl.[N-:45]=[N+]=[N-].[Na+].CS(O)(=O)=O>O>[NH2:7][C:8]1([C:18]2[S:19][C:20]([C:23]3[CH:28]=[C:27]([NH:29][C:30]4[N:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][N:31]=4)[CH:26]=[C:25]([CH3:40])[CH:24]=3)=[CH:21][N:22]=2)[CH2:17][CH2:16][NH:45][C:11](=[O:12])[CH2:10][CH2:9]1

参加物

6

反応物 4

HCID 6212ChloroformHCID 6395Methanesulfonic AcidHCID 33557Sodium AzideHCID 672609322-methyl-N-{8-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]dec-8-yl}propane-2-sulfinamide

生成物 1

HCID 584562585-Amino-5-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]azepan-2-one収率 66%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
65 °C

実験手順

To the product of Step 2 (100 mg, 0.13 mmol) was added chloroform (630 μL), sodium azide (24.5 mg, 0.38 mmol), and methanesulfonic acid (98 μL, 1.51 mmol). The mixture was heated to 65° C. for 1.5 h., cooled to room temperature, diluted with water, and extracted with ethyl acetate (2×). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was purified by reverse phase HPLC (35:65 to 70:30 acetonitrile:water with a 0.1% trifluoroacetic acid modifier). The fractions containing the desired product were diluted with ethyl acetate and free based with saturated aqueous sodium bicarbonate. The separated organic layer was dried over magnesium sulfate, filtered and concentrated to afford the title compound (38 mg, 0.083 mmol, 66% yield) as an orange oil. MS ESI: [M+H]+ m/z 463. 1H NMR (500 MHz, DMSO-d6) δ 10.26 (s, 1H), 8.83 (s, 1H), 8.75 (s, 1H), 8.02 (s, 1H), 7.93 (s, 1H), 7.49 (s, 1H), 7.28 (d, J=4.7, 1H), 7.16 (s, 1H), 2.39-2.08 (m, 9H), 1.30-0.99 (m, 4H). rhSYK activity=+++

後処理

  1. temperaturecooled to room temperature
  2. extractionextracted with ethyl acetate (2×)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by reverse phase HPLC (35:65 to 70:30 acetonitrile
  7. additionThe fractions containing the desired product
  8. additionwere diluted with ethyl acetate
  9. dry with materialThe separated organic layer was dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

出典と根拠

ORDレコード
ord-e9b053cd26284622b5043512c7c84b9f
出典データセット
uspto-grants-2014_06
特許番号
US08759366B2

反応ノート

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