Isonicotinic Acid → [2-(4-Fluorophenyl)-3-(4-pyridinyl)pyrazolo[1,5-a]pyridin-5-yl]methyl Isonicotinate

HRID 1374701ノート

反応式

HRID 1374701 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:18]([C:19]3[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=3)=[C:11]3[CH:12]=[C:13]([CH2:16][OH:17])[CH:14]=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.[N:25]1[CH:30]=[CH:29][C:28]([C:31](O)=[O:32])=[CH:27][CH:26]=1.C(P(=O)(OCC)OCC)#N.C(N(CC)CC)C>CN(C)C=O.CCCCCC.C(OCC)(=O)C>[C:31]([O:17][CH2:16][C:13]1[CH:14]=[CH:15][N:10]2[N:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[C:18]([C:19]3[CH:20]=[CH:21][N:22]=[CH:23][CH:24]=3)=[C:11]2[CH:12]=1)(=[O:32])[C:28]1[CH:29]=[CH:30][N:25]=[CH:26][CH:27]=1

参加物

7

反応物 4

HCID 5922Isonicotinic AcidHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 99667962-(4-Fluorophenyl)-5-hydroxymethyl-3-(4-pyridinyl)-pyrazolo[1,5-a]pyridine

生成物 1

HCID 10159364[2-(4-Fluorophenyl)-3-(4-pyridinyl)pyrazolo[1,5-a]pyridin-5-yl]methyl Isonicotinate

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 21226206Ethyl acetate hexane溶媒

実験手順

2-(4-Fluorophenyl)-5-hydroxymethyl-3-(4-pyridinyl)pyrazolo[1,5-a]pyridine (Example 6. 30 mg, 0.094 mmol) and 4-pyridinecarboxylic acid (0.12 mmol) are dissolved in dimethylformamide (0.5 mL) and diethyl cyanophosphonate (35 mg, 0.2 mmol, 93% grade), followed by triethylamine (35 mg, 0.35 mmol) are added dropwise. The resulting solution is stirred at room temperature until the reaction is complete as determined by TLC and then diluted with hexane/ethyl acetate (30 mL of a 1:1 mixture) and washed with water (3×). The organic phase is then shaken with dilute hydrochloric acid. In cases were the hydrochloride salt of the product deposits at this stage it is filtered off, washed with water and then hexane and dried. If no deposit is observed, the acidic phase is separated, washed once with hexane/ethyl acetate (15 mL of a 1:1 mixture) and basified with saturated sodium bicarbonate solution. This is then extracted with dichloromethane (15 mL) five times and the dichloromethane solution dried (MgSO4), filtered and concentrated to give the title compound. 1H NMR (d6-DMSO) δ 5.43 (s, 2H), 7.15 (d, J=6.9 Hz, 1H), 7.25 (t, J=8.8 Hz, 2H), 7.30 (d, J=5.9 Hz, 2H), 7.50–7.53 (m, 2H), 7.84–7.87 (m, 3H), 8.55 (d, J=5.7 Hz, 2H), 8.79 (d, J=5.9 Hz, 2H), 8.82 (d, J=7.1 Hz, 1H); APESI-MS m/z 425 (M+1)+.

後処理

  1. additionare added dropwise
  2. washwashed with water (3×)
  3. stirringThe organic phase is then shaken with dilute hydrochloric acid
  4. filtrationis filtered off
  5. washwashed with water
  6. dry with materialhexane and dried
  7. customthe acidic phase is separated
  8. washwashed once with hexane/ethyl acetate (15 mL of a 1:1 mixture) and
  9. extractionThis is then extracted with dichloromethane (15 mL) five times
  10. dry with materialthe dichloromethane solution dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-6a2fa1ed4e3545fea60581f505e652b3
出典データセット
uspto-grants-2007_01
特許番号
US07166597B2

反応ノート

読み込み中…