Pyridine → HCID 58290634, compound

HRID 876608Notes

Reaction equation

HRID 876608 reaction equation
C([O:4][C@H:5]([C@H:9]1[O:14][CH2:13][CH2:12][N:11]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[C:10]1=[O:25])[C:6](Cl)=[O:7])(=O)C.[NH2:26][C:27]1[CH:36]=[C:35]2[C:30]([C:31]([NH:37]C(=O)OC(C)(C)C)=[N:32][CH:33]=[N:34]2)=[CH:29][CH:28]=1.N1C=CC=CC=1.C(#N)C>ClCCl.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[NH2:37][C:31]1[C:30]2[C:35](=[CH:36][C:27]([NH:26][C:6](=[O:7])[C@H:5]([OH:4])[C@H:9]3[O:14][CH2:13][CH2:12][N:11]([C:15]4[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=4)[C:10]3=[O:25])=[CH:28][CH:29]=2)[N:34]=[CH:33][N:32]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 6342AcetonitrileHCID 58181639HCID 58181639, compound2×HCID 58181997HCID 58181997, compound

Product 1

HCID 58290634HCID 58290634, compoundYield 20.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of compound 98-6 (˜0.15 mmol) in 2 ml dichloromethane at 0° C. was added tert-butyl 7-aminoquinazolin-4-ylcarbamate (compound 98-4) (77 mg, 0.30 mmol, 2 eq.) followed by pyridine (24 μA, 0.30 mmol, 2 eq.) and DMAP (2 mg, 0.016 mmol, 0.1 eq.). To the mixture was added 1 ml of acetonitrile and stirred overnight while warming to rt. It was diluted with ethyl acetate, washed with aq. NaHCO3, water and brine, dried over MgSO4, filtered, concentrated to dryness. The residue was stirred overnight with 5 ml of 7N ammonia in methanol. The methanol was evaporated and the residue was stirred with 2 ml each of dichloromethane and trifluoroacetic acid for about 75 min. The mixture was evaporated to dryness and the residue was purified by RPHPLC to provide 14 mg of EXAMPLE 98.

Workup

  1. washwashed with aq. NaHCO3, water and brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. stirringThe residue was stirred overnight with 5 ml of 7N ammonia in methanol
  6. customThe methanol was evaporated
  7. stirringthe residue was stirred with 2 ml each of dichloromethane and trifluoroacetic acid for about 75 min
  8. customThe mixture was evaporated to dryness
  9. customthe residue was purified by RPHPLC

Sources & evidence

ORD record
ord-7bc2a0a7991a4b6c9527c3069687b762
Source dataset
uspto-grants-2015_03
Patent number
US08987242B2

Reaction notes

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