Ammonium Chloride → 2-methyl-2-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]propanamide

HRID 1962678Notes

Reaction equation

HRID 1962678 reaction equation
[CH3:1][C:2]([N:7]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]3[NH:18][CH:19]=[CH:20][C:13]=23)[CH:9]=[N:8]1)([CH3:6])[C:3](O)=[O:4].C1N=C[N:23](C(N2C=NC=C2)=O)C=1.[NH4+].[Cl-]>CN(C=O)C>[CH3:1][C:2]([N:7]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]3[NH:18][CH:19]=[CH:20][C:13]=23)[CH:9]=[N:8]1)([CH3:6])[C:3]([NH2:23])=[O:4]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 682631,1'-CarbonyldiimidazoleHCID 177547292-methyl-2-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]propanoic acid

Product 1

HCID 177546922-methyl-2-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]propanamideYield 26.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-methyl-2-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]propanoic acid (23 mg, 0.000085 mol) and N,N-carbonyldiimidazole (CDI) (21 mg, 0.00013 mol) in 2 mL of DMF was stirred for 3 hours. An excess of solid NH4Cl and TEA was added to the mixture and this was stirred for 3 hours. The majority of solvent was removed in vacuo, and the crude residue was purified by preparative-HPLC (C18 eluting with a gradient of ACN/H2O containing 0.1% TFA) followed by re-purification via preparative-HPLC (C18 eluting with a gradient of ACN/H2O containing 0.15% NH4OH) to afford 2-methyl-2-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]propanamide (6 mg, 26%). 1H NMR (400 MHz, d6-DMSO): 11.63 (s, 1H), 8.44 (s, 1H), 8.16 (s, 1H), 8.14 (s, 1H), 7.47 (t, 1H), 7.29 (d, 1H), 7.21 (s, 1H), 6.93 (s, 1H), 6.80 (dd, 1H), 1.77 (s, 6H); MS (ES): 270 (M+1).

Workup

  1. stirringthis was stirred for 3 hours
  2. customThe majority of solvent was removed in vacuo
  3. customthe crude residue was purified by preparative-HPLC (
  4. washC18 eluting with a gradient of ACN/H2O containing 0.1% TFA)
  5. customfollowed by re-purification via preparative-HPLC (
  6. washC18 eluting with a gradient of ACN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-ee13262c34b24862a149fc129eacbcea
Source dataset
uspto-grants-2013_04
Patent number
US08415362B2

Reaction notes

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