(5-Amino-2H-pyrazol-3-yl)-acetic acid → {3-[(7-{2-[1-(2-tert-butoxyethyl)piperidin-4-yl]ethoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acid

HRID 749162Notes

Reaction equation

HRID 749162 reaction equation
[C:1]([O:5][CH2:6][CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][O:16][C:17]2[C:18]([O:30][CH3:31])=[CH:19][C:20](C#N)=[C:21]([N:23]=[CH:24][N:25]([CH3:27])C)[CH:22]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[NH2:32][C:33]1[CH:37]=[C:36]([CH2:38][C:39]([OH:41])=[O:40])[NH:35][N:34]=1>C(O)(=O)C>[C:1]([O:5][CH2:6][CH2:7][N:8]1[CH2:9][CH2:10][CH:11]([CH2:14][CH2:15][O:16][C:17]2[CH:22]=[C:21]3[C:20]([C:27]([NH:32][C:33]4[CH:37]=[C:36]([CH2:38][C:39]([OH:41])=[O:40])[NH:35][N:34]=4)=[N:25][CH:24]=[N:23]3)=[CH:19][C:18]=2[O:30][CH3:31])[CH2:12][CH2:13]1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 16221512(5-Amino-2H-pyrazol-3-yl)-acetic acidHCID 68990930N'-(5-{2-[1-(2-tert-butoxyethyl)piperidin-4-yl]ethoxy}-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide

Product 1

HCID 68990806{3-[(7-{2-[1-(2-tert-butoxyethyl)piperidin-4-yl]ethoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acidYield 67.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

N′-(5-{2-[1-(2-tert-butoxyethyl)piperidin-4-yl]ethoxy}-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (654 mg, 1.5 mmol) in acetic acid (1.35 ml) was heated with (3-amino-1H-pyrazol-5-yl)acetic acid (214 mg, 1.52 mmol) at reflux for 45 minutes. Acetic acid was evaporated and the residue taken up in a mixture of dichloromethane:methanol. Excess diisopropylethylamine was added, and the solvent evaporated in vacuo. Dichloromethane was added to the solid, which was filtered and dried to yield {3-[(7-{2-[1-(2-tert-butoxyethyl)piperidin-4-yl]ethoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acid as a white powder (530 mg, 66% yield):

Workup

  1. temperatureat reflux for 45 minutes
  2. customAcetic acid was evaporated
  3. additionthe residue taken up in a mixture of dichloromethane
  4. additionExcess diisopropylethylamine was added
  5. customthe solvent evaporated in vacuo
  6. additionDichloromethane was added to the solid, which
  7. filtrationwas filtered
  8. customdried

Sources & evidence

ORD record
ord-9fc50b3d923740fab5c1f82f46ebfe29
Source dataset
uspto-grants-2008_07
Patent number
US07402585B2

Reaction notes

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