Thionyl Chloride → HCID 10166255, compound

HRID 1796540Notes

Reaction equation

HRID 1796540 reaction equation
Cl.Cl.[CH:3]1([NH:8][C:9]2[N:14]3[N:15]=[C:16]([C:30]4[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=4)[C:17]([C:18]4[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH:25]5[CH2:29][CH2:28][CH2:27][CH2:26]5)[N:19]=4)=[C:13]3[CH:12]=[CH:11][C:10]=2[C:37]([OH:39])=O)[CH2:7][CH2:6][CH2:5][CH2:4]1.S(Cl)(Cl)=O.[NH:44]1[CH2:48][CH2:47][CH2:46][CH2:45]1>ClCCl>[CH:3]1([NH:8][C:9]2[N:14]3[N:15]=[C:16]([C:30]4[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=4)[C:17]([C:18]4[CH:23]=[CH:22][N:21]=[C:20]([NH:24][CH:25]5[CH2:29][CH2:28][CH2:27][CH2:26]5)[N:19]=4)=[C:13]3[CH:12]=[CH:11][C:10]=2[C:37]([N:44]2[CH2:48][CH2:47][CH2:46][CH2:45]2)=[O:39])[CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 31268PyrrolidineHCID 67550289HCID 67550289, compound

Product 1

HCID 10166255HCID 10166255, compoundYield 49.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

7-(Cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-6-carboxylic acid dihydrochloride (19 mg, 0.033 mmol) was added to a dry flask and cooled to −78° C. Thionyl chloride (14 μL, 0.19 mmol) was added and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under a stream of nitrogen then placed under high vacuum. To a solution of the crude residue in dichloromethane (600 μL) was added pyrrolidine (150 μL, 1.80 mmol). The reaction mixture was stirred at room temperature for 10 minutes then partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with ethyl acetate. The combined extracts were washed with water and brine, then dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (1:1 hexanes:ethyl acetate to 100% ethyl acetate) provided N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)-6-(1-pyrrolidinylcarbonyl)pyrazolo[1,5-a]pyridin-7-amine (9 mg, 49%) as a clear oil. Rf 0.13 (1:1 hexanes:ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 8.04 (d, 1H), 7.72 (d, 1H), 7.62 (m, 2H), 7.26 (d, 1H), 7.14(t, 2H), 6.54(d, 1H), 6.30(d, 1H), 5.11 (d, 1H), 4.31 (m, 1H), 4.19 (m, 1H), 3.66 (broad, 2H), 3.38 (broad, 2H), 2.11–1.88 (m, 8H), 1.80–1.50 (m, 12H); MS m/z 554 (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. concentrationThe reaction mixture was concentrated under a stream of nitrogen
  2. stirringThe reaction mixture was stirred at room temperature for 10 minutes
  3. customthen partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washThe combined extracts were washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-3490cef41b9042dbb13581572bf4e424
Source dataset
uspto-grants-2006_04
Patent number
US07030134B2

Reaction notes

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