Triethylamine → 6-fluoro-2-{(7S)-7-methyl-8-[2-(2H-1,2,3-triazol-2-yl)benzoyl]-5,8-diazaspiro[2.6]non-5-yl}quinazoline

HRID 1808923Notes

Reaction equation

HRID 1808923 reaction equation
[CH3:1][C@@H:2]1[N:10]([C:11](=[O:23])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:18]2[N:22]=[CH:21][CH:20]=[N:19]2)[CH2:9][C:6]2([CH2:8][CH2:7]2)[CH2:5][N:4]([C:24](OC(C)(C)C)=O)[CH2:3]1.ClC1[N:41]=[CH:40][C:39]2[C:34](=[CH:35][CH:36]=[C:37]([F:42])[CH:38]=2)[N:33]=1.C(N(CC)CC)C>C(Cl)Cl.C(O)(C(F)(F)F)=O.CN(C=O)C.CCOC(C)=O>[F:42][C:37]1[CH:38]=[C:39]2[C:34](=[CH:35][CH:36]=1)[N:33]=[C:24]([N:4]1[CH2:3][C@H:2]([CH3:1])[N:10]([C:11](=[O:23])[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:18]3[N:22]=[CH:21][CH:20]=[N:19]3)[CH2:9][C:6]3([CH2:7][CH2:8]3)[CH2:5]1)[N:41]=[CH:40]2

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 179135522-Chloro-6-fluoroquinazolineHCID 59527662tert-butyl (7S)-7-methyl-8-[2-(2H-1,2,3-triazol-2-yl)benzoyl]-5,8-diazaspiro[2.6]nonane-5-carboxylate

Product 1

HCID 426033296-fluoro-2-{(7S)-7-methyl-8-[2-(2H-1,2,3-triazol-2-yl)benzoyl]-5,8-diazaspiro[2.6]non-5-yl}quinazoline

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.03 g (2.5 mmol) 2-5 in 50 mL CH2Cl2 and 5 mL TFA was allowed to stir at room temperature overnight. The solvents were removed by rotary evaporation, the residue was basified with saturated aqueous Na2CO3, and extracted with three portions of 2:1 CHCl3/EtOH. The organic extracts were concentrated, redissolved in CH2Cl2, filtered and concentrated to provide 765 mg of a taffy. A solution of 116 mg (0.37 mmol) of this material in 3 mL DMF was treated with 68 mg (0.37 mmol) of 1-8 and 130 mL (0.93 mmol) triethylamine and stirred at 60° C. overnight. After cooling to room temperature, the reaction was diluted with EtOAc, washed with saturated aqueous NaHCO3, then with water, brine and dried over Na2SO4. Following concentration by rotary evaporation, the residue was purified by flash column chromatography (EtOAc/hexanes) to provide 2-6 as a pale yellow solid. Data for 2-6: HRMS (APCI) m/z (M+H) 458.2103 found; 458.2099 required.

Workup

  1. customThe solvents were removed by rotary evaporation
  2. extractionextracted with three portions of 2:1 CHCl3/EtOH
  3. concentrationThe organic extracts were concentrated
  4. dissolutionredissolved in CH2Cl2
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto provide 765 mg of a taffy
  8. stirringstirred at 60° C. overnight
  9. temperatureAfter cooling to room temperature
  10. washwashed with saturated aqueous NaHCO3
  11. dry with materialwith water, brine and dried over Na2SO4
  12. concentrationconcentration
  13. customby rotary evaporation
  14. customthe residue was purified by flash column chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-0d79bbeff2e248bcb58e04b2adcd52b3
Source dataset
uspto-grants-2013_01
Patent number
US08362009B2

Reaction notes

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