Borohydride → HCID 178473725, compound

HRID 849426Notes

Reaction equation

HRID 849426 reaction equation
[ClH:1].Cl.Cl.[NH:4]1[CH:8]=[C:7]([CH2:9][N:10]2[C:16]3[CH:17]=[CH:18][C:19]([C:21]4[CH:22]=N[CH:24]=[CH:25][CH:26]=4)=[CH:20][C:15]=3[CH2:14][N:13]([C:27](=[O:32])[C:28](F)(F)F)[CH:12]([CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:11]2)[N:6]=[CH:5]1.[CH:40](C1N=CNC=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[BH4-]>ClCCl.O.C(O)(=O)C>[ClH:1].[C:27]([N:13]1[CH2:14][C:15]2[CH:20]=[C:19]([C:21]3[CH:22]=[CH:40][CH:24]=[CH:25][CH:26]=3)[CH:18]=[CH:17][C:16]=2[N:10]([CH2:9][C:7]2[N:6]=[CH:5][NH:4][CH:8]=2)[CH2:11][C@H:12]1[CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)(=[O:32])[CH3:28]

Participants

8

Reactant 4

HCID 28123Borohydride2×HCID 764281H-Imidazole-4-carbaldehyde2×HCID 5049666Sodium triacetoxyborohydrideHCID 178478619HCID 178478619, compound

Product 1

HCID 178473725HCID 178473725, compoundYield 94%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of Compound B (5.3 g, 11.7 mmol) in dichloromethane (100 mL) were added acetic acid (15 mL) and 4-formylimidazole (1.15 g, 12 mmol). After 10 min, sodium triacetoxyborohydride (2.54 g, 12 mmol) was added. After 3 hr, 4-formylimidazole (0.5 g, 5.8 mmol) and borohydride (1.2 g, 5.5 mmol) were added. After 18 hr, aldehyde (0.5 g) and borohydride (1.2 g) were added. After 5 hr, the mixture was concentrated. Aqueous ammonia (100 mL) and chloroform (100 mL) were added to the residue and the mixture was stirred vigorously for 0.5 hr. The two layers were separated and the organic layer was washed again with aqueous ammonia (100 mL). The combined aqueous layer was extracted with chloroform (100 mL), the two organic extracts were combined, dried (K2CO3), and concentrated. The residue was purified by flash silica gel column chromatography (step gradient of 5% and 10% MeOH in chloroform) to afford a solid which was dissolved in dichloromethane (50 mL) and HCl gas was bubbled through the solution. The mixture was concentrated in vacuo to afford a solid which was dissolved in water and lyophilized to afford Compound C (5.2 g, 73%). MS: (M+H)+ 532

Workup

  1. waitAfter 3 hr
  2. waitAfter 18 hr
  3. waitAfter 5 hr
  4. concentrationthe mixture was concentrated
  5. additionAqueous ammonia (100 mL) and chloroform (100 mL) were added to the residue
  6. customThe two layers were separated
  7. washthe organic layer was washed again with aqueous ammonia (100 mL)
  8. extractionThe combined aqueous layer was extracted with chloroform (100 mL)
  9. dry with materialdried (K2CO3)
  10. concentrationconcentrated
  11. customThe residue was purified by flash silica gel column chromatography (step gradient of 5% and 10% MeOH in chloroform)
  12. customto afford a solid which
  13. customHCl gas was bubbled through the solution
  14. concentrationThe mixture was concentrated in vacuo
  15. customto afford a solid which

Sources & evidence

ORD record
ord-94f2fcca00214f3c86b6fb037cb2c25f
Source dataset
uspto-grants-2000_01
Patent number
US06011029

Reaction notes

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