Thionyl Chloride → HCID 10276916, compound

HRID 1797073Notes

Reaction equation

HRID 1797073 reaction equation
S(Cl)(Cl)=O.[CH:5]1([NH:10][C:11]2[N:16]=[C:15]([C:17]3[C:18]([C:30]4[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=4)=[N:19][N:20]4[C:25]([CH3:26])=[C:24]([C:27](O)=[O:28])[CH:23]=[CH:22][C:21]=34)[CH:14]=[CH:13][N:12]=2)[CH2:9][CH2:8][CH2:7][CH2:6]1.[CH:37]1([NH2:40])[CH2:39][CH2:38]1>ClCCl>[CH:5]1([NH:10][C:11]2[N:16]=[C:15]([C:17]3[C:18]([C:30]4[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=4)=[N:19][N:20]4[C:25]([CH3:26])=[C:24]([C:27]([NH:40][CH:37]5[CH2:39][CH2:38]5)=[O:28])[CH:23]=[CH:22][C:21]=34)[CH:14]=[CH:13][N:12]=2)[CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 69828CyclopropylamineHCID 10274363HCID 10274363, compound

Product 1

HCID 10276916HCID 10276916, compoundYield 44.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Thionyl chloride (200 μL, 2.7 mmol) was added to 3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)-7-methylpyrazolo[1,5-a]pyridine-6-carboxylic acid (31 mg, 0.072 mmol) which had been pre-cooled to 0° C. The reaction mixture was stirred at room temperature for 1 hour. The excess thionyl chloride was removed in vacuo. To a solution of the residue in dichloromethane (300 μL) was added cyclopropylamine (50 uL, 0.72 mmol). The reaction mixture was stirred at room temperature for 30 minutes. The resultant mixture was quenched with water and diluted with ethyl acetate. Saturated aqueous sodium bicarbonate solution was added to the biphasic mixture. The organic layer was washed with water and brine, then dried over magnesium sulfate. Filtration and concentration, followed by flash chromatography (3:2 hexanes:ethyl acetate to 2:3 hexanes:ethyl acetate) provided 3-[2-(cyclopentylamino)-4-pyrimidinyl]-N-cyclopropyl-2-(4-fluorophenyl)-7-methylpyrazolo[1,5-a]pyridine-6-carboxamide (15 mg, 44%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.28 (d, 1H), 8.05 (d, 1H), 7.62 (m, 2H), 7.30 (d, 1H), 7.13 (t, 2H), 6.29 (d, 1H), 5.10 (d, 1H), 4.30 (m, 1H), 2.96 (s, 3H), 2.94 (m, 1H), 2.05 (m, 2H), 1.76–1.50 (m, 6H), 0.92 (m, 2H), 0.66 (m, 2H); MS m/z 471 (M+1).

Workup

  1. customThe excess thionyl chloride was removed in vacuo
  2. stirringThe reaction mixture was stirred at room temperature for 30 minutes
  3. customThe resultant mixture was quenched with water
  4. additiondiluted with ethyl acetate
  5. additionSaturated aqueous sodium bicarbonate solution was added to the biphasic mixture
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-ac2dfc9bfa09409b988ded539b2d68ca
Source dataset
uspto-grants-2006_04
Patent number
US07034030B2

Reaction notes

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