Hydrochloric Acid → HCID 21075326, compound

HRID 1373709Notes

Reaction equation

HRID 1373709 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:18][C:19]([CH:21]2[CH2:26][CH2:25]C(=O)[CH2:23][CH2:22]2)=[O:20])=[C:6]([CH:17]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=1)=[O:8].[CH3:28][N:29]1[CH2:35][CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.[BH3-][C:37]#N.[Na+].[ClH:40]>C(Cl)Cl.CO>[ClH:1].[ClH:40].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:18][C:19]([CH:21]2[CH2:26][CH2:25][CH:28]([N:29]3[CH2:35][CH2:34][CH2:33][N:32]([CH3:37])[CH2:31][CH2:30]3)[CH2:23][CH2:22]2)=[O:20])=[C:6]([CH:17]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=1)=[O:8]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 2283491-Methylhomopiperazine2×HCID 5003444Sodium cyanoborohydride2×HCID 21075333HCID 21075333, compound

Product 1

HCID 21075326HCID 21075326, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 5-chloro-2-[4-oxocyclohexylcarbonylamino]-N-(5-chloropyridin-2-yl)benzamide (600 mg, 1.5 mmol), 1-methyl-hexahydro-1,4-diazepine (0.57 mL, 4.6 mmol), methanol (30 mL) and methylene chloride (15 mL) was added NaCNBH3 (66 mg, 1.05 mmol) and the mixture was stirred for four days. To the reaction mixture was added additional 1-methyl-hexahydro-1,4-diazapine (0.19 mL, 1.5 mmol) followed by NaCNBH3 (22 mg, 0.35 mmol) and the mixture was stirred for 1 day. The reaction mixture was acidified with 1 N HCl, stirred for 1 h, and then concentrated in vacuo. To the residue was added methylene chloride and the resulting solution was washed with satd Na2CO3 solution. The organic layer was concentrated and chromatographed on 60 g silica gel (CH2Cl2 to 5% 2 M NH3/MeOH in CH2Cl2) followed by further HPLC purification (Vydac C18; 5% CH3CN/(0.1% TFA in H2O) to 70% CH3CN/(0.1% TFA in H2O).; Rt: 20.3 min) to give the title compound as a solid (340 mg, 39%).

Workup

  1. stirringthe mixture was stirred for 1 day
  2. stirringstirred for 1 h
  3. concentrationconcentrated in vacuo
  4. additionTo the residue was added methylene chloride
  5. washthe resulting solution was washed with satd Na2CO3 solution
  6. concentrationThe organic layer was concentrated
  7. customchromatographed on 60 g silica gel (CH2Cl2 to 5% 2 M NH3/MeOH in CH2Cl2)
  8. customfollowed by further HPLC purification (Vydac C18; 5% CH3CN/(0.1% TFA in H2O) to 70% CH3CN/(0.1% TFA in H2O).; Rt: 20.3 min)

Sources & evidence

ORD record
ord-fb98595fa8f54322bfd1527520a51e80
Source dataset
uspto-grants-2007_01
Patent number
US07163938B2

Reaction notes

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