Acetic Acid → HCID 10298014, compound

HRID 723995Notes

Reaction equation

HRID 723995 reaction equation
Cl.Cl.[CH:3]1([NH:8][C:9]2[N:14]=[C:13]([C:15]3[C:16]([C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)=[N:17][N:18]4[CH:23]=[C:22]([NH2:24])[CH:21]=[CH:20][C:19]=34)[CH:12]=[CH:11][N:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4]1.[C:32]1(=O)[CH2:36][CH2:35][CH2:34][CH2:33]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH:32]1([NH:24][C:22]2[CH:21]=[CH:20][C:19]3[N:18]([N:17]=[C:16]([C:25]4[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=4)[C:15]=3[C:13]3[CH:12]=[CH:11][N:10]=[C:9]([NH:8][CH:3]4[CH2:7][CH2:6][CH2:5][CH2:4]4)[N:14]=3)[CH:23]=2)[CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8452CyclopentanoneHCID 5049666Sodium triacetoxyborohydrideHCID 131726109HCID 131726109, compound

Product 1

HCID 10298014HCID 10298014, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a suspension of 3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-6-amine dihydrochloride (90 mg, 0.20 mmol) in 1,2-dichloroethane was added cyclopentanone (26 μL, 0.29 mmol), acetic acid (56 μL, 0.98), and sodium triacetoxyborohydride (82 mg, 0.39 mmol). The reaction mixture was stirred at room temperature 16 hours then quenched with water. The resultant mixture was diluted with ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic layer was separated and washed with water and brine. The organic layer was dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (4:1 hexanes:ethyl acetate to 7:3 hexanes:ethyl acetate) provided N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-6-amine (40 mg, 45%) as a green oil. Rf 0.25 (2:1 hexanes:ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 8.25 (d, 1H), 8.00 (d, 1H), 7.79 (s, 1H), 7.61 (m, 2H), 7.13 (t, 2H), 6.86 (d, 1H), 6.32 (d, 1H), 5.23 (br, 1H), 4.36 (m, 1H), 3.72 (m, 1H), 3.54 (d, 1H), 2.14–2.02 (m, 4H), 1.81–1.51 (m, 12H); MS m/z 457 (M+1). To a solution of the product in ether was added 1 M HCl in ether. The precipitated solid was isolated to give the corresponding HCl salt.

Workup

  1. customthen quenched with water
  2. additionThe resultant mixture was diluted with ethyl acetate and saturated aqueous sodium bicarbonate solution
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-c10cfa871e2f4713a662946f3c14fa08
Source dataset
uspto-grants-2006_11
Patent number
US07141569B2

Reaction notes

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