4-Methylmorpholine → 2-(3-((7-(3-chloropropoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide

HRID 1864479Notes

Reaction equation

HRID 1864479 reaction equation
CN1CCOCC1.[F:8][C:9]1[CH:10]=[C:11]([CH:13]=[CH:14][CH:15]=1)[NH2:12].Cl.[Cl:17][CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:31]=[C:30]2[C:25]([C:26]([NH:32][C:33]3[CH:37]=[C:36]([CH2:38][C:39](O)=[O:40])[NH:35][N:34]=3)=[N:27][CH:28]=[N:29]2)=[CH:24][CH:23]=1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C1C=CN=CC=1.CN(C)C(=O)C.O.C(#N)C>[Cl:17][CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:31]=[C:30]2[C:25]([C:26]([NH:32][C:33]3[CH:37]=[C:36]([CH2:38][C:39]([NH:12][C:11]4[CH:13]=[CH:14][CH:15]=[C:9]([F:8])[CH:10]=4)=[O:40])[NH:35][N:34]=3)=[N:27][CH:28]=[N:29]2)=[CH:24][CH:23]=1

Participants

9

Reactant 4

HCID 79724-MethylmorpholineHCID 97423-FluoroanilineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67000008(3-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid hydrochloride

Product 1

HCID 162214542-(3-((7-(3-chloropropoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 31374DimethylacetamideSolvent

Procedure

4-Dimethylaminopyridine (DMAP), N-methylmorpholine and 3-fluoroaniline (in a large excess) were added to a suspension of (3-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid.hydrochloride in N,N-dimethylacetamide (DMA) and the resulting slurry was stirred at or below room temperature. A solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI.HCl) previously dissolved in water was then added in a controlled manner over a period of 8 hour so as to maintain the reaction at ambient temperature. The mixture was seeded with a small amount of product and left to stir for several hours. Anti-solvent acetonitrile followed by water were also added to precipitate more product. The material was isolated by filtration and the cake washed with a mixture of N,N-dimethylacetamide:water:acetonitrile, warm acetonitrile and then dried (in vacuo or under a stream of nitrogen) to yield 2-(3-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide.

Workup

  1. additionwas then added in a controlled manner over a period of 8 hour so as
  2. temperatureto maintain
  3. customthe reaction at ambient temperature
  4. waitleft
  5. stirringto stir for several hours
  6. additionwere also added
  7. customto precipitate more product
  8. customThe material was isolated by filtration
  9. washthe cake washed with a mixture of N,N-dimethylacetamide
  10. temperaturewater:acetonitrile, warm acetonitrile
  11. customdried (in vacuo

Sources & evidence

ORD record
ord-3ec6c6d8208c404b9b61880d1c0b3b5b
Source dataset
uspto-grants-2009_12
Patent number
US07625910B2

Reaction notes

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