Aniline → HCID 67696640, compound

HRID 343215Notes

Reaction equation

HRID 343215 reaction equation
[C:1](Cl)(=O)[C:2](Cl)=O.C([C:10](C1C=CC(OC)=CC=1)([C:36](=[O:38])[NH2:37])[N:11]1[C:17](=[O:18])[C:16]([CH2:20][C:21]([OH:23])=O)([CH3:19])[C:15](=[O:24])[N:14]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)[C:13]2[CH:32]=[CH:33][CH:34]=[CH:35][C:12]1=2)(C)C.C[N:48]([CH:50]=O)C.N[C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>C(Cl)Cl.Cl>[O:18]=[C:17]1[N:11]([CH2:10][C:36]([N:37]([CH:16]([CH3:17])[CH3:15])[C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)=[O:38])[C:12]2[CH:35]=[CH:34][CH:33]=[CH:32][C:13]=2[N:14]([C:25]2[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=2)[C:15](=[O:24])[C:16]1([CH3:19])[CH2:20][C:21](=[O:23])[NH:48][C:50]1[CH:2]=[CH:1][CH:35]=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 6115AnilineHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 67700213HCID 67700213, compound

Product 1

HCID 67696640HCID 67696640, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

0.59 mL (6.7 mmol) of oxalyl chloride in 25 mL of CH2Cl2 is added dropwise to a solution of 1.8 g (3.4 mmol) of [1-(Isopropyl-(4-methoxy-phenyl)-carbamoylmethyl)-3-methyl-2,4-dioxo-5-(4-chloro-phenyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-acetic acid, prepared as in Intermediate 3, and 0.013 mL of DMF in 50 ml of CH2Cl2 cooled to 0° C. The solution is stirred at RT for 2.5 h and subsequently concentrated in vacuo to a dark grey foam. The crude acid chloride is dissolved in 60 mL of CH2Cl2, cooled to 0° C. and a solution of 0.92 mL (10.1 mmol) of aniline in 15 mL of CH2Cl2 is added dropwise. The mixture is stirred at RT for 2 h. After diluting with 200 mL of 1N HCl, the mixture is extracted with EtOAc (×2). The organic extract is washed with 1N HCl and brine, dried over MgSO4 and concentrated in vacuo to a grey foam. Purification by silica gel flash chromatography (50% EtOAc/petroleum ether) followed by recrystallization from EtOAc/petroleum ether gave 1.14 g of the title compound as a white powder: m.p. 170°-6° C.; 1H NMR (CDCl3 300 MHz) δ7.88 (s, 1H), 7.6-6.8 (m, 17H), 5.01 (m, 1H), 4.65 (d, 1H, J=17), 3.84 (s, 3H), 3.82 (d, 1H, J=17), 2.45 (q, 2H, J=15), 1.67 (s, 3H), 1.11 (m, 6H); low resolution MS (FAB) m/e 639 (MH+).

Workup

  1. concentrationsubsequently concentrated in vacuo to a dark grey foam
  2. dissolutionThe crude acid chloride is dissolved in 60 mL of CH2Cl2
  3. temperaturecooled to 0° C.
  4. stirringThe mixture is stirred at RT for 2 h
  5. extractionthe mixture is extracted with EtOAc (×2)
  6. extractionThe organic extract
  7. washis washed with 1N HCl and brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo to a grey foam
  10. customPurification by silica gel flash chromatography (50% EtOAc/petroleum ether)
  11. customfollowed by recrystallization from EtOAc/petroleum ether

Sources & evidence

ORD record
ord-f60a48fd3a764609a95382b8c5bbcfa9
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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