Hydrochloric Acid → HCID 16221452, compound

HRID 749177Notes

Reaction equation

HRID 749177 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([NH:16][C:17]3[CH:21]=[C:20]([CH2:22][C:23]([OH:25])=[O:24])[NH:19][N:18]=3)=[N:11][CH:12]=[N:13]2)=[CH:8][C:7]=1[O:26][CH3:27].[OH:28][CH2:29][CH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.Cl>CC(N(C)C)=O>[OH:28][CH2:29][CH:30]1[CH2:35][CH2:34][N:33]([CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:15]=[C:14]3[C:9]([C:10]([NH:16][C:17]4[CH:21]=[C:20]([CH2:22][C:23]([OH:25])=[O:24])[NH:19][N:18]=4)=[N:11][CH:12]=[N:13]3)=[CH:8][C:7]=2[O:26][CH3:27])[CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4207714-PiperidinemethanolHCID 16221450HCID 16221450, compound

Product 1

HCID 16221452HCID 16221452, compoundYield 69.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

(3-{[7-(3-chloropropoxy)-6-methoxyquinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid (7.83 g, 20 mmol) in dimethylacetamide (30 ml) was reacted with 4-(hydroxymethyl)piperidine (8.05 g, 70 mmol) at 100° C. for 2 hours. The solvent was evaporated, and the residue triturated with a mixture of dichloromethane:ethyl acetate (1:1). The paste was recovered, and dissolved in a mixture of dichloromethane:methanol. Ethanolic HCl (7.0 N) (10 ml, 70 mmol) was added to the mixture and the solvents were evaporated. Methanol (200 ml) was added to the solid and the mixture was stirred for 0.5 hour. The reaction mixture was reduced in volume and dichloromethane added. The resultant solid was recovered by filtration and dried to yield {3-[(7-{3-[4-(hydroxymethyl)piperidin-1-yl]propoxy}-6-methoxyquinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetic acid (6.5 g, 60% yield) as a yellow solid:

Workup

  1. customThe solvent was evaporated
  2. customthe residue triturated with a mixture of dichloromethane:ethyl acetate (1:1)
  3. customThe paste was recovered
  4. dissolutiondissolved in a mixture of dichloromethane
  5. customthe solvents were evaporated
  6. additionMethanol (200 ml) was added to the solid
  7. additionadded
  8. filtrationThe resultant solid was recovered by filtration
  9. customdried

Sources & evidence

ORD record
ord-521bd13d2e85475b8b3ea61b5c39a6ac
Source dataset
uspto-grants-2008_07
Patent number
US07402585B2

Reaction notes

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