Potassium Carbonate → HCID 10142538, compound

HRID 1062861Notes

Reaction equation

HRID 1062861 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.Cl.[NH2:45][OH:46].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.ClCCl.C(OCC)(=O)C>[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[CH2:26][CH2:27][CH2:28][CH2:29]5)[N:19]=4)=[C:13]3[CH:12]=[CH:11][C:10]=2[C:37]([NH:45][OH:46])=[O:39])[CH2:7][CH2:6][CH2:5][CH2:4]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 443297Hydroxyamine hydrochlorideHCID 67550289HCID 67550289, compound

Product 1

HCID 10142538HCID 10142538, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

7-(Cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-6-carboxylic acid dihydrochloride (52 mg, 0.091 mmol) was added to a dry flask and cooled to −78° C. Thionyl chloride (38 μL, 0.52 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. In a separate flask, a suspension of hydroxylamine hydrochloride (29 mg, 0.42 mmol) and potassium carbonate (29 mg, 0.21 mmol) in tetrahydrofuran (600 μL) was stirred at room temperature for 30 minutes. To this suspension was added a solution of the crude acid chloride in dichloromethane (600 μL). The resulting mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate solution, water, and brine. The organic layer was dried over magnesium sulfate. Filtration and concentration followed by chromatography (100% ethyl acetate to 9:1 ethyl acetate:methanol) provided 7-(cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)-N-hydroxypyrazolo[1,5-a]pyridine-6-carboxamide (12 mg, 26%) as a brownish-yellow solid. Rf 0.42 (19:1 ethyl acetate: methanol); 1H NMR (400 MHz, CDCl3): δ 8.05 (broad 2H), 7.60 (m, 2H), 7.50 (broad, 1H), 7.21 (broad, 1H), 7.13 (t, 2H), 6.29 (d, 1H), 5.91 (broad, 1H), 4.92 (broad, 1H), 4.31 (m, 1H), 2.10-1.97 (broad, 4H), 1.82-1.54 (broad, 12H); MS m/z 516 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated under a stream of nitrogen
  2. stirringwas stirred at room temperature for 30 minutes
  3. stirringThe resulting mixture was stirred at room temperature for 16 hours
  4. washwashed with saturated aqueous sodium bicarbonate solution, water, and brine
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-8c48150f0c114143acb84ece43e84f94
Source dataset
uspto-grants-2005_11
Patent number
US06962914B2

Reaction notes

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