Diethyl Ether → N-Cyclopentyl-3-(2-(cyclopentylamino)-4-pyrimidinyl)-2-(4-fluorophenyl)pyrazolo(1,5-a)pyridin-7-amine

HRID 1373788

反応式

HRID 1373788 の反応式
[CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)[C:15]([C:16](=O)/[CH:17]=[CH:18]/N(C)C)=[C:11]3[CH:10]=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH:31]1([NH:36][C:37]([NH2:39])=[NH:38])[CH2:35][CH2:34][CH2:33][CH2:32]1.CC(C)([O-])C.[K+].CCOCC>O1CCCC1.O>[CH:1]1([NH:6][C:7]2[N:12]3[N:13]=[C:14]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)[C:15]([C:16]4[CH:17]=[CH:18][N:39]=[C:37]([NH:36][CH:31]5[CH2:35][CH2:34][CH2:33][CH2:32]5)[N:38]=4)=[C:11]3[CH:10]=[CH:9][CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

参加物

7

反応物 4

HCID 3283Diethyl EtherHCID 11372773(2E)-1-[7-(cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-3-(dimethylamino)-2-propen-1-oneHCID 23665647Potassium tert-butoxideHCID 178479367HCID 178479367、化合物

生成物 1

HCID 5275682N-Cyclopentyl-3-(2-(cyclopentylamino)-4-pyrimidinyl)-2-(4-fluorophenyl)pyrazolo(1,5-a)pyridin-7-amine収率 91.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of (2E)-1-[7-(cyclopentylamino)-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-3-(dimethylamino)-2-propen-1-one (3.5 g, 8.9 mmol) in tetrahydrofuran (36 mL, 0.25 M) was added N-cyclopentylguanidine hydrochloride (1.89 g, 11.6 mmol), followed by solid potassium tert-butoxide (2.6 g, 23.2 mmol) in two portions. The resultant solution was heated to reflux for 23 hours. Upon cooling to room temperature, ether was added followed by water. The organics were washed with brine, and the aqueous layer was extracted with ether. The combined organics were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica to give N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-7-amine (3.7 g, 91%) as an off white solid. 1H NMR (CDCl3): δ 7.97 (d, 1H), 7.68 (d, 1H), 7.59 (dd, 2H), 7.27 (t, 1H), 7.10 (t, 2H), 6.24 (d, 1H), 5.99 (d, 1H), 5.96 (d, 1H), 5.01 (d, 1H), 4.28 (m, 1H), 3.97 (m, 1H), 2.12–1.99 (m, 4H), 1.79–1.44 (m, 12H); 13C NMR (CDCl3) δ 163.12 (d, JCF=246.6 Hz), 162.09, 161.53, 156.67, 152.15, 142.66, 141.09, 131.46 (d, JCF=8.0 Hz), 129.92 (d, JCF=3.1 Hz), 128.39, 115.45(d, JCF=21.3 Hz), 108.68, 107.13, 105.15, 90.13, 53.84, 52.87, 33.50, 33.30, 24.05, 23.70; 19F NMR (CDCl3) δ −113.49; MS m/z 457 (M+1); Anal. Calcd for C27H29FN6: C, 71.03; H, 6.40; N, 18.41. Found: C, 71.20; H, 6.37; N, 18.52.

後処理

  1. temperatureto reflux for 23 hours
  2. washThe organics were washed with brine
  3. extractionthe aqueous layer was extracted with ether
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica

出典と根拠

ORDレコード
ord-6b7839f129a44eabab9972cc2d5cea99
出典データセット
uspto-grants-2007_01
特許番号
US07163940B2

関連ノート

読み込み中…