3-{[(2-amino-4-tert-butylphenyl)carbamoyl]methyl}-N-methoxy-N-methylcyclobutane-1-carboxamide → HCID 178502664, compound

HRID 511629Notes

Reaction equation

HRID 511629 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[NH:12][C:13]([CH2:15][CH:16]1[CH2:19][CH:18]([C:20]([N:22]([O:24][CH3:25])[CH3:23])=[O:21])[CH2:17]1)=O>C(O)(=O)C>[C:8]([C:6]1[CH:5]=[CH:4][C:3]2[NH:12][C:13]([CH2:15][CH:16]3[CH2:19][CH:18]([C:20]([N:22]([O:24][CH3:25])[CH3:23])=[O:21])[CH2:17]3)=[N:1][C:2]=2[CH:7]=1)([CH3:11])([CH3:10])[CH3:9]

Participants

3

Reactant 1

HCID 866661223-{[(2-amino-4-tert-butylphenyl)carbamoyl]methyl}-N-methoxy-N-methylcyclobutane-1-carboxamide

Product 1

HCID 178502664HCID 178502664, compoundYield 116.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A stirred solution of 3-{[(2-amino-4-tert-butylphenyl)carbamoyl]methyl}-N-methoxy-N-methylcyclobutane-1-carboxamide (70%, 2.62 g, 5.28 mmol) in acetic acid (25 ml) was heated to reflux for 1 h. The reaction mixture was concentrated under reduced pressure, and the residue partitioned between sat. NaHCO3 (aq) (25 ml) and EtOAc (25 ml), and the layers separated. The aqueous layer was extracted with EtOAc (2×25 ml), the combined organics were washed with brine (50 ml), dried (MgSO4) and concentrated. The crude material was purified by silica flash column chromatography, eluting with 1-10% 2M NH3 in MeOH in DCM to afford the title compound (2.02 g, 93%) as a yellow gum: MS (ESI+) for C19H27N3O2 m/z 330.5 [M+H]+; LC purity 80% (UV), 100% (ELS), (ret. time, 1.51 min); 1H NMR (500 MHz, CHLOROFORM-d) δH ppm 7.56 (br. s., 1H), 7.48 (d, J=8.5 Hz, 1H), 7.30 (dd, J=8.5, 1.7 Hz, 1H), 3.80-3.90 (m, 1H), 3.65 (s, 3H), 3.47-3.57 (m, 1H), 3.20 (s, 3H), 2.94-3.13 (m, 2H), 2.88 (dt, J=16.1, 8.1 Hz, 1H), 2.32-2.60 (m, 2H), 2.01-2.17 (m, 2H), 1.38 (s, 9H).

Workup

  1. temperatureto reflux for 1 h
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe residue partitioned between sat. NaHCO3 (aq) (25 ml) and EtOAc (25 ml)
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted with EtOAc (2×25 ml)
  6. washthe combined organics were washed with brine (50 ml)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe crude material was purified by silica flash column chromatography
  10. washeluting with 1-10% 2M NH3 in MeOH in DCM

Sources & evidence

ORD record
ord-e58fea016af54770b1f4f9ad7fe97d4a
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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