Picolyl chloride → HCID 58404720, compound

HRID 1253532Notes

Reaction equation

HRID 1253532 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[C:6]2[N:7]([N:17]=[CH:18][C:19]=2[C:20]2[CH:21]=[N:22][NH:23][CH:24]=2)[CH:8]=[C:9]([C:11]2[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=2)[CH:10]=1.Cl[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1>O1CCCC1>[CH3:3][O:4][C:5]1[C:6]2[N:7]([N:17]=[CH:18][C:19]=2[C:20]2[CH:21]=[N:22][N:23]([CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=3)[CH:24]=2)[CH:8]=[C:9]([C:11]2[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=2)[CH:10]=1

Participants

5

Reactant 3

HCID 23393Picolyl chlorideHCID 24758Sodium hydrideHCID 58404718HCID 58404718, compound

Product 1

HCID 58404720HCID 58404720, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred suspension of NaH (60% dispersion in mineral oil, 0.004 g, 0.1 mmol) in tetrahydrofuran (2.0 mL) was added a solution of 4-Methoxy-6-(1-methyl-1H-pyrazol-4-yl)-3-(1H-pyrazol-4-yl)-pyrazolo[1,5-a]pyridine (15 mg, 0.05 mmol) in tetrahydrofuran (1.0 mL) at 0° C. The resultant slurry was then stirred at ambient temperature for 15 min followed by the addition of 2-(chloromethyl)pyridine (0.007 g, 0.055 mmol) in tetrahydrofuran (1.0 mL). The reaction mixture was heated to 60° C. After 8 hours, the reaction mixture was cooled and quenched with ice water and the organic components were extracted with ethyl acetate (2×10 mL) and the combined organic layers were concentrated. The crude material was purified by flash column chromatography (methanol/dichloromethane gradient) to afford 4-Methoxy-6-(1-methyl-1H-pyrazol-4-yl)-3-(1-pyridin-2-ylmethyl-1H-pyrazol-4-yl)-pyrazolo[1,5-a]pyridine. 1H NMR (400 MHz, CD3OD) δ 8.56 (bs, 2H), 8.34 (s, 1H), 8.07-8.02 (m, 2H), 7.91 (s, 1H), 7.86-7.83 (m, 2H), 7.38 (bs, 1H), 7.17 (bs, 1H), 6.79 (s, 1H), 5.51 (s, 2H), 4.01 (s, 3H), 3.96 (s, 3H). LRMS (ESI) calculated for C21H19N7O [M+H]+, 386.2; found 386.5. The compounds in the following table were prepared according to the procedure described in scheme 6 and for compounds 6-1 to 6-4. The compounds were prepared as free bases.

Workup

  1. temperatureThe reaction mixture was heated to 60° C
  2. waitAfter 8 hours
  3. temperaturethe reaction mixture was cooled
  4. customquenched with ice water
  5. extractionthe organic components were extracted with ethyl acetate (2×10 mL)
  6. concentrationthe combined organic layers were concentrated
  7. customThe crude material was purified by flash column chromatography (methanol/dichloromethane gradient)

Sources & evidence

ORD record
ord-2f96ddb6618d4409b5fe9ed683982bc5
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

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