Citric Acid → HCID 67263712, compound

HRID 1041607Notes

Reaction equation

HRID 1041607 reaction equation
[CH3:1][O:2][C:3]1[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][C:6]2[NH:7][C:8](=[O:12])[CH2:9][NH:10][CH2:11][C:5]=2[CH:4]=1.C(N(CC)C(C)C)(C)C.[C:27](Cl)(=[O:29])[CH3:28].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl>[C:27]([N:10]1[CH2:11][C:5]2[CH:4]=[C:3]([O:2][CH3:1])[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][C:6]=2[NH:7][C:8](=[O:12])[CH2:9]1)(=[O:29])[CH3:28]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 67264267HCID 67264267, compound

Product 1

HCID 67263712HCID 67263712, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a slurry of 7-methoxy-8-nitro-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one (100 mg, 0.42 mmol) in dichloromethane (10 mL) was syringed N,N-diisopropylethylamine (0.15 mL, 0.84 mmol). The mixture was cooled in an ice-water bath and acetyl chloride (0.04 mL, 0.55 mmol) was added via syringe. After 15 minutes LCMS indicated completion of the reaction. Dichloromethane (10 mL) and 10% aqueous citric acid (10 mL) were added and the mixture was stirred while being allowed to warm to room temperature. The mixture was filtered and the collected solid was washed with water and dried to constant weight to give 4-acetyl-7-methoxy-8-nitro-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one (70 mg, 60%) as a yellow solid. NMR analysis indicated a mixture of two conformational isomers, similar to that observed for the related trifluoroacetyl analog (see procedure 6c); NMR (400 MHz, DMSO-d6) δ 10.19/10.17 (2s, 1H), 7.69/7.66 (2s, 1H), 7.46/7.35 (2s, 1H), 4.78/4.67 (2s, 2H), 4.36/4.37 (2s, 2H), 3.90/3.92 (2s, 3H), 2.05 (s, 3H); MS (m/e) 278 (M−1); mp 266° C. (dec.).

Workup

  1. temperatureThe mixture was cooled in an ice-water bath
  2. customcompletion of the reaction
  3. filtrationThe mixture was filtered
  4. washthe collected solid was washed with water
  5. customdried to constant weight

Sources & evidence

ORD record
ord-443c72e57d21410ab9d6712921321b49
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

Loading…