Dimethylformamide → HCID 57781126, compound

HRID 1690744Notes

Reaction equation

HRID 1690744 reaction equation
[CH3:1][C:2]1([CH3:21])[CH:11]([N:12]2[C:16]([C:17]([OH:19])=O)=[CH:15][N:14]=[CH:13]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:20])[O:3]1.CN(C)C=O.C(Cl)(=O)C(Cl)=O.[CH2:33]([NH2:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>ClCCl>[CH2:33]([NH:40][C:17]([C:16]1[N:12]([CH:11]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:4](=[O:20])[O:3][C:2]2([CH3:21])[CH3:1])[CH:13]=[N:14][CH:15]=1)=[O:19])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7504BenzylamineHCID 65578Oxalyl chlorideHCID 19864122HCID 19864122, compound

Product 1

HCID 57781126HCID 57781126, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

3-(3,3-Dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carboxylic acid (0.100 g, 0.349 mmol) (Example 23) is dissolved in dichloromethane (2 mL). Catalytic amount of dimethylformamide (0.002 mL, 0.0262 mmol) is added to the reaction mixture and cooled to 0° C. Oxalyl chloride (0.076 mL, 0.874 mmol) is added and the cooling bath is removed. The mixture is stirred at room temperature for 2 h and then concentrated in vacuo. The residue obtained is redissolved in dichloromethane and benzylamine (0.114 mL, 1.04 mmol) is added. Reaction mixture is stirred at room temperature for 1 h. The mixture is washed with saturated aqueous sodium bicarbonate and extracted with dichloromethane. The combined organic phase is dried over Na2SO4 and concentrated in vacuo. The residue is purified by silica gel chromatography (dichlormethane-methanol, 19:1) to give 3-(3,3-dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carboxylic acid benzylamide; MS (ESI) m/z 376.0 (M+H); 1H NMR (400 MHz, MeOD) δ ppm 1.24 (s, 3 H), 1.53 (s, 3 H), 4.62 (s, 2 H), 6.98 (s, 1 H), 7.26-7.35 (m, 1 H), 7.35-7.46 (m, 5 H), 7.57 (d, J=7.6 Hz, 1 H), 7.64-7.73 (m, 2 H), 7.74-7.84 (m, 1 H), 8.26 (dd, J=7.8, 1.5 Hz, 1 H).

Workup

  1. customthe cooling bath is removed
  2. concentrationconcentrated in vacuo
  3. customThe residue obtained
  4. customReaction mixture
  5. stirringis stirred at room temperature for 1 h
  6. washThe mixture is washed with saturated aqueous sodium bicarbonate
  7. extractionextracted with dichloromethane
  8. dry with materialThe combined organic phase is dried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified by silica gel chromatography (dichlormethane-methanol, 19:1)

Sources & evidence

ORD record
ord-9fea143659194f7091ca69150d00d79d
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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