Acetic Acid → HCID 67575036, compound

HRID 609658Notes

Reaction equation

HRID 609658 reaction equation
[C:1]([O:5][C:6](=[O:28])[NH:7][CH2:8][CH2:9][NH:10][CH2:11][CH2:12][CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([N:23]3[CH:27]=[N:26][N:25]=[CH:24]3)[CH:21]=2)[NH:16][CH:15]=1)([CH3:4])([CH3:3])[CH3:2].[CH:29](=O)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:28])[NH:7][CH2:8][CH2:9][N:10]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:11][CH2:12][CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([N:23]3[CH:27]=[N:26][N:25]=[CH:24]3)[CH:21]=2)[NH:16][CH:15]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 240Benzaldehyde3×HCID 5003444Sodium cyanoborohydrideHCID 10715052HCID 10715052, compound

Product 1

HCID 67575036HCID 67575036, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-[(3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl)amino]ethyl carbamic acid tert-butyl ester (0.42 g, 1.2 mmol) in methanol (10 ml) at 0° C. was added benzaldehyde (133 μl, 1.3 mmol), acetic acid (189 μl, 3.3 mmol) and sodium cyanoborohydride (137 mg, 2.2 mmol). After addition the cooling bath was removed and the mixture stirred for 4 h. After this time more benzaldehyde (110 μl, 1.1 mmol) was added and the mixture stirred for 18 h. More benzaldehyde (110 μl, 1.1 mmol) was added and the mixture stirred for a further 10 min. The solvents were evaporated and the residue partitioned between EtOAc (2×50 ml) and water (50 ml). The combined organic layers were dried (Na2SO4) and evaporated. The residue was chromatographed on silica gel, eluting with CH2Cl2 :MeOH:NH3 (95:5:1), to give the desired product (0.44 g, 85%) as a pale yellow foam. 1H NMR (360 MHz, CDCl3) δ1.41 (9H, s), 1.84-1.96 (2H, m), 2.52-2.58 (4H, m), 2.75 (2H, t, J=7.5 Hz), 3.12-3.20 (2H, m), 3.58 (2H, s), 4.78 (1H, br s), 7.03 (1H, s), 7.14 (1H, dd, J=8.5 and 2.0 Hz), 7.21-7.36 (5H, m), 7.45 (1H, d, J=8.5 Hz), 7.51 (1H, d, J=2.0 Hz), 8.29 (1H, br s), 8.45 (2H, s). MS (ES+) (475, M+1).

Workup

  1. additionAfter addition the cooling bath
  2. customwas removed
  3. stirringthe mixture stirred for 18 h
  4. stirringthe mixture stirred for a further 10 min
  5. customThe solvents were evaporated
  6. customthe residue partitioned between EtOAc (2×50 ml) and water (50 ml)
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. customevaporated
  9. customThe residue was chromatographed on silica gel
  10. washeluting with CH2Cl2 :MeOH:NH3 (95:5:1)

Sources & evidence

ORD record
ord-c0cf97c524cc47b3941a814bbb240db0
Source dataset
uspto-grants-1999_12
Patent number
US05998415

Reaction notes

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