Acetic Acid → HCID 86756045, compound

HRID 1857994Notes

Reaction equation

HRID 1857994 reaction equation
[N:1]1[N:2]=[CH:3][N:4]([C:6]2[CH:7]=[C:8]3[C:12](=[CH:13][CH:14]=2)[NH:11][CH:10]=[C:9]3[CH2:15][CH:16]2[CH2:23][CH:22]3[CH:18]([CH2:19][N:20]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:21]3)[NH:17]2)[CH:5]=1.[C:29](O)(=O)C.C=O.O.C([BH3-])#N.[Na+]>CO>[CH3:29][N:17]1[CH:16]([CH2:15][C:9]2[C:8]3[C:12](=[CH:13][CH:14]=[C:6]([N:4]4[CH:3]=[N:2][N:1]=[CH:5]4)[CH:7]=3)[NH:11][CH:10]=2)[CH2:23][CH:22]2[CH:18]1[CH2:19][N:20]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:21]2

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 86756046HCID 86756046, compound

Product 1

HCID 86756045HCID 86756045, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of (1RS,3RS,5RS)-3-[{5-(1,2,4-triazol-4-yl)-1H-indol-3-yl}methyl]-2,7-diazabicyclo[3.3.0]octane-7-carboxylic acid, ethyl ester (1.6514 g, 4.34 mmol) in methanol (70 mL) was added glacial acetic acid (0.99 mL, 17.3 mmol), 37% solution of formaldehyde in water (0.423 mL, 5.64 mmol) and sodium cyanoborohydride (0.3309 g, 5.27 mmol). The mixture was stirred at room temperature under argon for 3.5 h before quenching with saturated K2CO3 solution (200 mL) and extracting with EtOAc (3×50 mL). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, CH2Cl2 --MeOH--NH3 (aq); 95:5:0.5 then 94:6:0.6) to give 1.4723 g (86.0%) of the title compound as a cream solid. δH (250 MHz, CDCl3) 1.23 (3H, t), 1.63 (1H, m), 1.84-1.96 (1H, m), 2.52 (3H, s), 2.59 (1H, m), 3.78 (1H, m), 4.10 (2H, q, J=7.0 Hz), 7.14-7.20 (2H, m), 7.50 (1H, d, J=12.6 Hz), 7.52 (1H, s), 8.48 (2H, s), 8.63 (1H, br s). m/e (ES+) 395 (M+H)+.

Workup

  1. custombefore quenching with saturated K2CO3 solution (200 mL)
  2. extractionextracting with EtOAc (3×50 mL)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. customevaporated in vacuo
  5. customThe residue was purified by flash chromatography (silica gel, CH2Cl2

Sources & evidence

ORD record
ord-919d46f7aa6e4ddf9441c57076c6c1f7
Source dataset
uspto-grants-2000_11
Patent number
US06150391

Reaction notes

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