Dimethylamine → HCID 11854509, compound

HRID 1157466Notes

Reaction equation

HRID 1157466 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=O)=[CH:4][C:3]=1[C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]=[C:15]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=1)[N:14]([CH2:28][C:29]([NH:31][CH:32]([CH3:34])[CH3:33])=[O:30])[C:13]2=[O:35].[CH3:36][NH:37][CH3:38].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(O)(=O)C>[CH3:36][N:37]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[C:15]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=2)[N:14]([CH2:28][C:29]([NH:31][CH:32]([CH3:33])[CH3:34])=[O:30])[C:13]3=[O:35])[CH:4]=1)[CH3:38]

Participants

6

Reactant 3

HCID 674DimethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 59511774HCID 59511774, compound

Product 1

HCID 11854509HCID 11854509, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 2-[6-(2-fluoro-5-formylphenyl)-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide (19 mg, 0.04 mmol) in dichloroethane (2 mL) and acetic acid (0.05 mL) was added dimethylamine (2M in acetonitrile, 0.50 mL, 1.0 mmol) and the reaction mixture was stirred at room temperature for 30 minutes. Sodium triacetoxyborohydride (70 mg, 0.33 mmol) was then added as a solid with stirring at room temperature for 24 h. The solvent was removed in vacuo, the residue partitioned between ethyl acetate and a 1 N NaOH (aq.), the organic layer was washed with brine, dried (MgSO4) and the solvent evaporated. The resulting residue was subjected to preparative HPLC purification to provide 2-[6-(5-dimethylaminomethyl-2-fluorophenyl)-2-(3-methoxyphenyl)-4-oxo-4H-quinazolin-3-yl]-N-isopropylacetamide (EXAMPLE 6a) (10 mg, 0.02 mmol, 50%).

Workup

  1. stirringwith stirring at room temperature for 24 h
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between ethyl acetate
  4. washa 1 N NaOH (aq.), the organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent evaporated
  7. customThe resulting residue was subjected to preparative HPLC purification

Sources & evidence

ORD record
ord-9916abbe2b754bd498d4e5a6b4fd0a61
Source dataset
uspto-grants-2010_10
Patent number
US07807686B2

Reaction notes

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