Hydrochloric Acid → HCID 86692191, compound

HRID 470919Notes

Reaction equation

HRID 470919 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[CH2:16][N:15]([C:18]([O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])=[O:19])[CH2:14][C:13]([CH3:28])([CH3:27])[C:12]=3[N:11]=[C:10]([CH:29]([CH3:31])[CH3:30])[C:9]=2[CH:32]=[O:33])=[CH:4][CH:3]=1.C[Si]([C:38]#[N:39])(C)C.CO.Cl>C(Cl)Cl.[I-].[Zn+2].[I-]>[C:38]([CH:32]([OH:33])[C:9]1[C:10]([CH:29]([CH3:30])[CH3:31])=[N:11][C:12]2[C:13]([CH3:28])([CH3:27])[CH2:14][N:15]([C:18]([O:20][CH2:21][CH2:22][Si:23]([CH3:24])([CH3:25])[CH3:26])=[O:19])[CH2:16][C:17]=2[C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)#[N:39]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 82115Trimethylsilyl cyanide2×HCID 58993130HCID 58993130, compound2×

Product 1

HCID 86692191HCID 86692191, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 9883512zinc(II)iodideCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(trimethylsilyl)ethyl 4-(4-fluorophenyl)-3-formyl-2-isopropyl-8,8-dimethyl-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (intermediate 1) (4.28 g, 9.09 mmol), trimethylsilyl cyanide (1.46 ml, 10.91 mmol) and zinc iodide (0.145 g, 0.455 mmol) in CH2Cl2 (5 mL) was stirred at room temperature for 2.5 h. MeOH (100 mL) was added and the reaction stirred 22 h at room temperature. Additional trimethylsilyl cyanide (2 mL) was added and stirring continued at room temperature for 24 h. 1M HCl (10 mL) was added and stirring continued for 24 h. The reaction mixture was concentrated and the residue taken up in Et2O (200 mL), washed with satd NaHCO3 (50 mL), water (25 mL), brine (25 mL), dried (Na2SO4), filtered and solvent removed to give 2-(trimethylsilyl)ethyl 3-(cyano(hydroxy)methyl)-4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (4.16 g) as a tan powder contaminated with about 20% of starting material. This was used in the next step without further purification.

Workup

  1. stirringthe reaction stirred 22 h at room temperature
  2. stirringstirring
  3. waitcontinued at room temperature for 24 h
  4. stirringstirring
  5. waitcontinued for 24 h
  6. concentrationThe reaction mixture was concentrated
  7. washwashed with satd NaHCO3 (50 mL), water (25 mL), brine (25 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customsolvent removed

Sources & evidence

ORD record
ord-744e1f40ea6e4e2b8201300ae5f8e035
Source dataset
uspto-grants-2014_01
Patent number
US08629276B2

Reaction notes

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