Hydrochloric Acid → HCID 42638914, compound

HRID 660031Notes

Reaction equation

HRID 660031 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][N:17]2[C:25]3[C:20](=[CH:21][C:22]([C:26]4[NH:27][C:28]([CH3:41])=[C:29]([C:31]5[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=5)[N:30]=4)=[CH:23][CH:24]=3)[CH:19]=[CH:18]2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.C=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(O)=O.ClC(Cl)C.C(O)(=O)C>[CH3:6][N:8]1[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][CH2:16][N:17]2[C:25]3[C:20](=[CH:21][C:22]([C:26]4[NH:27][C:28]([CH3:41])=[C:29]([C:31]5[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:39])([F:40])[F:38])[CH:32]=5)[N:30]=4)=[CH:23][CH:24]=3)[CH:19]=[CH:18]2)[CH2:12][CH2:13]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 68874485HCID 68874485, compound

Product 1

HCID 42638914HCID 42638914, compoundYield 42%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 284Formic AcidSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 4-(3-{5-[5-methyl-4-(3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-indol-1-yl}-propyl)-piperazine-1-carboxylic acid tert-butyl ester (91 mg, 0.16 mmol) in formic acid (2 mL) was added 4 M HCl (0.5 mL). The mixture was stirred for 30 min. The mixture was concentrated and the residue was partitioned between CHCl3 (2×) and 1 M NaOH (5 mL). The combined organic layers were dried and concentrated to give a crude product (52 mg). To a solution of this crude material in dichloroethane (3 mL) was added acetic acid (1 drop) and formaldehyde (37% in water; 0.04 mL, 0.60 mmol) followed by Na(OAc)3BH (127 mg, 0.60 mmol). The resulting mixture was stirred for 2 h before neutralizing with satd. aq. NaHCO3 and extracting with 10% isopropanol in CHCl3 (2×10 mL). The combined organic extracts were dried and concentrated, and purified by FCC to afford 32 mg (42%) of the title compound.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between CHCl3 (2×) and 1 M NaOH (5 mL)
  3. customThe combined organic layers were dried
  4. concentrationconcentrated
  5. customto give a crude product (52 mg)
  6. stirringThe resulting mixture was stirred for 2 h
  7. extractionaq. NaHCO3 and extracting with 10% isopropanol in CHCl3 (2×10 mL)
  8. customThe combined organic extracts were dried
  9. concentrationconcentrated
  10. custompurified by FCC

Sources & evidence

ORD record
ord-44f8ce3572214fc48a00368054317a78
Source dataset
uspto-grants-2011_12
Patent number
US08084466B2

Reaction notes

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