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

HRID 1373788노트

반응식

HRID 1373788 반응식
[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

참가 물질

7

반응물 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, 화합물

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-6b7839f129a44eabab9972cc2d5cea99
출처 데이터셋
uspto-grants-2007_01
특허 번호
US07163940B2

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