Acetic Acid → HCID 68738536, compound

HRID 240792Notes

Reaction equation

HRID 240792 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:12]=[N:13][N:14]([CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH:15]=3)[CH:9]=2)[N:4](C(OC(C)(C)C)=O)[N:3]=1.[CH:30]1([CH:33]=O)[CH2:32][CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.Cl>ClCCCl>[CH2:16]([N:14]1[CH:15]=[C:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][N:3]=[C:2]3[NH:1][CH2:33][CH:30]2[CH2:32][CH2:31]2)[N:12]=[N:13]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 123114CyclopropanecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 68737159HCID 68737159, compound

Product 1

HCID 68738536HCID 68738536, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of Example 64A (100 mg, 0.256 mmol), cyclopropanecarbaldehyde (0.057 mL, 0.76 mmol), sodium triacetoxyborohydride (163 mg, 0.76 mmol) and acetic acid (0.044 mL, 0.76 mmol) in 1,2-dichloroethane (5 mL) was stirred at ambient temperature for about 2.5 hours. Hydrochloric acid (4 N in dioxane, 4 mL) was added and the reaction mixture was stirred for about 16 hours. The precipitate was collected by filtration, rinsing with ether (10 mL). The solid was dissolved in dichloromethane (10 mL) and treated with trifluoroacetic acid (0.1 mL) and the reaction mixture was stirred at room temperature for about 2 hours. The reaction mixture was neutralized by the addition of 15% aqueous sodium hydroxide solution (about 15 mL) and the organic layer was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by reverse-phase HPLC using acetonitrile/water (0.05 M ammonium acetate) gradient elution method to afford the title compound as the acetate salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.43 (s, 1H), 8.41 (s, 1H), 8.28 (s, 1H), 7.68 (d, J=8.7 Hz, 1H), 7.32-7.45 (m, 5H), 7.26 (d, J=8.6 Hz, 1H), 6.08 (t, J=5.7 Hz, 1H), 5.64 (s, 2H), 3.12 (t, J=6.2 Hz, 2H), 1.04-1.22 (m, 1H), 0.35-0.53 (m, 2H), 0.17-0.32 (m, 2H). MS (ESI+) m/z 345 (M+H)+.

Workup

  1. filtrationThe precipitate was collected by filtration
  2. washrinsing with ether (10 mL)
  3. dissolutionThe solid was dissolved in dichloromethane (10 mL)
  4. additiontreated with trifluoroacetic acid (0.1 mL)
  5. stirringthe reaction mixture was stirred at room temperature for about 2 hours
  6. additionThe reaction mixture was neutralized by the addition of 15% aqueous sodium hydroxide solution (about 15 mL)
  7. customthe organic layer was separated
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude material was purified by reverse-phase
  12. washacetonitrile/water (0.05 M ammonium acetate) gradient elution method

Sources & evidence

ORD record
ord-453e7469b87a41cea6092afbc5e0e2d0
Source dataset
uspto-grants-2014_02
Patent number
US08648069B2

Reaction notes

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