Diisopropylethylamine → HCID 66614853, compound

HRID 473141Notes

Reaction equation

HRID 473141 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:14]([F:23])([F:22])[C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=2)[N:3]=1.[NH2:24][C:25]1[CH:29]=[C:28]([CH3:30])[N:27]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[N:26]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:22][C:14]([F:23])([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=1)[C:4]1[N:3]=[C:2]([NH:24][C:25]2[CH:29]=[C:28]([CH3:30])[N:27]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[N:26]=2)[C:11]2[C:6](=[CH:7][C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 113215371H-Pyrazole-1-carboxylicacid,3-amino-5-methyl-,1,1-dimethylethylesterHCID 866626954-Chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazoline

Product 1

HCID 66614853HCID 66614853, compoundYield 22.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 4-chloro-2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazoline (355 mg, 0.91 mmol) in DMF (5.0 mL) at rt were added tert-butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate (0.448 g, 2.27 mmol) and DIEA (0.40 mL, 2.3 mmol), and the mixture was stirred at rt for 3 h. The mixture was purified by preparative reverse-phase HPLC using TFA as a modifier, and the fractions containing the desired product were neutralized with saturated aq NaHCO3 and extracted with EtOAc (100 mL). The organic layer was separated, washed with brine (2×10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to afford tert-butyl 3-(2-(difluoro(5-fluoropyridin-2-yl)methyl)-7-methoxyquinazolin-4-ylamino)-5-methyl-1H-pyrazole-1-carboxylate as a clear oil (104 mg).

Workup

  1. customThe mixture was purified by preparative reverse-phase
  2. additionthe fractions containing the desired product
  3. extractionextracted with EtOAc (100 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (2×10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-07cc98f28b644b879f27e7422a20608e
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

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