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

HRID 1373788Notes

Reaction equation

HRID 1373788 reaction equation
[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

Participants

7

Reactant 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, compound

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-6b7839f129a44eabab9972cc2d5cea99
Source dataset
uspto-grants-2007_01
Patent number
US07163940B2

Reaction notes

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