Hydrochloric Acid → HCID 70178460, compound

HRID 2227397Notes

Reaction equation

HRID 2227397 reaction equation
[Si:1]([O:18]C(C1CNC(=O)CN1)C1C=CC=CC=1Cl)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:34]([C:36]1[CH:41]=[CH:40][C:39]([C:42]([NH:53]S(C(C)(C)C)=O)([C:47]2[N:51]([CH3:52])[CH:50]=[N:49][CH:48]=2)[CH2:43][CH2:44][CH:45]=O)=[CH:38][C:37]=1[F:60])#[N:35].[BH3-][C:62]#[N:63].[Na+].[ClH:65].[CH3:66][OH:67]>O1CCOCC1.CC(O)=O>[NH2:53][C:42]([C:39]1[CH:40]=[CH:41][C:36]([C:34]#[N:35])=[C:37]([F:60])[CH:38]=1)([C:47]1[N:51]([CH3:52])[CH:50]=[N:49][CH:48]=1)[CH2:43][CH2:44][CH2:45][N:49]1[CH2:48][CH2:47][N:63]([CH2:62][C:36]2[CH:41]=[C:40]([O:18][Si:1]([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:39]=[CH:38][C:37]=2[Cl:65])[C:66](=[O:67])[CH2:50]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 887Methanol2×HCID 5003444Sodium cyanoborohydrideHCID 18473245HCID 18473245, compoundHCID 131723364HCID 131723364, compound

Product 1

HCID 70178460HCID 70178460, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

1-(5-{[tert-Butyl(diphenyl)silyloxy}-2-chlorobenzyl)piperazin-2-one (0.052 g, 0.108 mmol) and N-[1-(4-cyano-3-fluorophenyl)-4-oxo-1-(1-methyl-1H-imidazol-5-yl)butyl]-2-methylpropane-2-sulfinamide (Example 1, Step J) (0.028 g, 0.0.072 mmol)were dissolved in MeOH (5 mL), the pH of the solution adjusted to 5 with HOAc, then NaCNBH3 (0.0068 g, 0.108 mmol) was added. After stirring at ambient temperature for 18 h, the reaction mixture was concentrated in vacuo, partitioned between CH2Cl2 and aqueous saturated NaHCO3 solution, the aqueous layer washed with CH2Cl2 (2×), the organic layers combined and dried (MgSO4). Filtration and concentration in vacuo gave the protected product which was dissolved in MeOH, treated with 4M HCl in dioxane (2 mL), stirred for 1.5 h, concentrated in vacuo, partitioned between CH2Cl2 and aqueous saturated NaHCO3 solution, the aqueous layer washed with CH2Cl2 (2×), the organic layers combined and dried (MgSO4). Filtration and concentration in vacuo, gave the title compound after chromatography on the ISCO Combiflash eluting with 1-5% MeOH/CH2Cl2 with NH4OH. MS(M+1) 749.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. custompartitioned between CH2Cl2 and aqueous saturated NaHCO3 solution
  3. washthe aqueous layer washed with CH2Cl2 (2×)
  4. dry with materialdried (MgSO4)
  5. filtrationFiltration and concentration in vacuo
  6. customgave the protected product which
  7. stirringstirred for 1.5 h
  8. concentrationconcentrated in vacuo
  9. custompartitioned between CH2Cl2 and aqueous saturated NaHCO3 solution
  10. washthe aqueous layer washed with CH2Cl2 (2×)
  11. dry with materialdried (MgSO4)
  12. filtrationFiltration and concentration in vacuo

Sources & evidence

ORD record
ord-5f53b729a0be4c9db43bd39271fcdeaf
Source dataset
uspto-grants-2002_07
Patent number
US06413964B1

Reaction notes

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