Isobutyryl chloride → N-[4-(1-ethyl-4-{2-[4-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]-2-methylpropanamide

HRID 1727731Notes

Reaction equation

HRID 1727731 reaction equation
[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH:22]=[CH:21][C:20]([CH2:23][N:24]5[CH2:28][CH2:27][CH2:26][CH2:25]5)=[CH:19][CH:18]=4)=[CH:16][C:9]=23)[C:5]([C:29]2[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][CH:30]=2)=[N:4]1)[CH3:2].[CH3:36][CH:37]([CH3:41])[C:38](Cl)=[O:39]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH:18]=[CH:19][C:20]([CH2:23][N:24]5[CH2:28][CH2:27][CH2:26][CH2:25]5)=[CH:21][CH:22]=4)=[CH:16][C:9]=23)[C:5]([C:29]2[CH:30]=[CH:31][C:32]([NH:33][C:38](=[O:39])[CH:37]([CH3:41])[CH3:36])=[CH:34][CH:35]=2)=[N:4]1)[CH3:2]

Participants

5

Reactant 2

HCID 62325Isobutyryl chlorideHCID 68995250HCID 68995250, compound

Product 1

HCID 58980014N-[4-(1-ethyl-4-{2-[4-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]-2-methylpropanamideYield 43%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a cloudy orange mixture of 4-(1-ethyl-4-{2-[4-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)aniline (280 mg, 0.61 mmol) in dry CH2Cl2 (6 mL) was added TEA (253 uL, 1.82 mmol), DMAP (4 mg, 0.03 mmol) and 2-methylpropanoyl chloride (77 uL, 0.73 mmol). The reaction was stirred for 15 min at room temperature, quenched with water and diluted with CH2Cl2 and brine. The aqueous layer was extracted with CH2Cl2 followed by 1% MeOH in CH2Cl2 and the combined extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by Gilson reverse phase HPLC (MeCN/H2O with 0.1% TFA). The clean fractions were neutralized with aqueous NaHCO3, extracted with three portions of CH2Cl2 followed by 1% MeOH in CH2Cl2, dried (Na2SO4), filtered and concentrated under reduced pressure to give 139 mg (43%) of the title product as a yellow solid. ESMS [M+H]+: 533.4.

Workup

  1. customquenched with water
  2. additiondiluted with CH2Cl2 and brine
  3. extractionThe aqueous layer was extracted with CH2Cl2
  4. dry with materialthe combined extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by Gilson reverse phase HPLC (MeCN/H2O with 0.1% TFA)
  8. extractionextracted with three portions of CH2Cl2
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9293f791bdf24cae93e4f6b7c0585a06
Source dataset
uspto-grants-2009_02
Patent number
US07495102B2

Reaction notes

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