8-Cyclopentyl-6-(2-ethoxy-ethoxy)-2-methanesulfinyl-8H-pyrido[2,3-d]pyrimidin-7-one → 4-{6-[8-Cyclopentyl-6-(2-ethoxy-ethoxy)-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino]-pyridin-3-yl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1271962ノート

反応式

HRID 1271962 の反応式
[CH:1]1([N:6]2[C:11]3[N:12]=[C:13](S(C)=O)[N:14]=[CH:15][C:10]=3[CH:9]=[C:8]([O:19][CH2:20][CH2:21][O:22][CH2:23][CH3:24])[C:7]2=[O:25])[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][N:36]([C:39]2[CH:40]=[N:41][C:42]([NH2:45])=[CH:43][CH:44]=2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]>C1(C)C=CC=CC=1.C(Cl)Cl>[C:26]([O:30][C:31]([N:33]1[CH2:38][CH2:37][N:36]([C:39]2[CH:40]=[N:41][C:42]([NH:45][C:13]3[N:14]=[CH:15][C:10]4[CH:9]=[C:8]([O:19][CH2:20][CH2:21][O:22][CH2:23][CH3:24])[C:7](=[O:25])[N:6]([CH:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)[C:11]=4[N:12]=3)=[CH:43][CH:44]=2)[CH2:35][CH2:34]1)=[O:32])([CH3:29])([CH3:27])[CH3:28]

参加物

5

反応物 2

HCID 112338858-Cyclopentyl-6-(2-ethoxy-ethoxy)-2-methanesulfinyl-8H-pyrido[2,3-d]pyrimidin-7-oneHCID 11737525tert-Butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate

生成物 1

HCID 111807254-{6-[8-Cyclopentyl-6-(2-ethoxy-ethoxy)-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino]-pyridin-3-yl}-piperazine-1-carboxylic acid tert-butyl ester収率 22%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒3 回HCID 6344Dichloromethane溶媒

反応条件

温度
110 °C

実験手順

8-Cyclopentyl-6-(2-ethoxy-ethoxy)-2-methanesulfinyl-8H-pyrido[2,3-d]pyrimidin-7-one (1.2 mL of a 0.46 M solution in toluene, 0.552 mmol) and 4-(6-amino-pyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (0.307 g, 1.1 mmol) were combined in toluene under nitrogen and heated to 110° C. After 4 h the toluene was replaced by xylenes (1 mL) and heating was continued under reflux overnight. After cooling to room temperature the crude reaction mixture was dissolved in CH2Cl2 and washed with saturated aqueous ammonium chloride solution then with brine. The organic layer was dired (MgSO4), filtered and evaporated to dryness. Chromotagraphy on silica gel eluting with 5% CH3OH in CH2Cl2 followed by a second chromatography step eluting with ethyl acetate provided 4-{6-[8-cyclopentyl-6-(2-ethoxy-ethoxy)-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino]-pyridin-3-yl}-piperazine-1-carboxylic acid tert-butyl ester (70 mg, 22%) as a yellow solid. MS (APCI); M++1: Calc'd, 580.32, Found 580.2. 1H NMR: δ (400 MHz, DMSO) 8.50 (s, 1H), 8.26 (d, J=9 Hz, 1H), 7.94 (d, J=3 Hz, 1H), 7.39 (dd, J=3,9 Hz, 1H), 6.78 (s, 1H), 5.89–5.98 (m, 1H), 4.15 (t, J=5 Hz, 2H), 3.86 (t, J=5 Hz, 2H), 3.56–3.62 (m, 6H), 3.09 (br t, J=5 Hz, 4H), 2.29–2.33 (m, 2H), 2.07–2.10 (m, 2H), 1.84–1.92 (m, 2H), 1.63–1.69 (m, 2H), 1.47 (s, 9H), 1.22 (t, J=7 Hz, 3H).

後処理

  1. temperatureheating
  2. temperatureunder reflux overnight
  3. temperatureAfter cooling to room temperature the crude
  4. customreaction mixture
  5. washwashed with saturated aqueous ammonium chloride solution
  6. filtrationfiltered
  7. customevaporated to dryness
  8. washeluting with ethyl acetate

出典と根拠

ORDレコード
ord-4d54cb7a5e804fb697109c50c1e4226e
出典データセット
uspto-grants-2007_04
特許番号
US07208489B2

反応ノート

読み込み中…