1-Methylimidazole → HCID 10674302, compound

HRID 366827Notes

Reaction equation

HRID 366827 reaction equation
Cl[C:2]([O:4][CH2:5][CH:6]1[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[CH:10][CH:11]=2)=[O:3].CN1C=CN=C1.[NH2:25][C:26]1[C:27]2[CH:47]=[CH:46][CH:45]=[CH:44][C:28]=2[C:29]2[CH:30]([CH2:42][Cl:43])[CH2:31][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:33]=2[CH:34]=1>C(Cl)Cl>[C:38]([O:37][C:35]([N:32]1[C:33]2[CH:34]=[C:26]([NH:25][C:2]([O:4][CH2:5][CH:6]3[C:18]4[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=4[C:12]4[C:7]3=[CH:8][CH:9]=[CH:10][CH:11]=4)=[O:3])[C:27]3[CH:47]=[CH:46][CH:45]=[CH:44][C:28]=3[C:29]=2[CH:30]([CH2:42][Cl:43])[CH2:31]1)=[O:36])([CH3:41])([CH3:40])[CH3:39]

Participants

5

Reactant 3

HCID 13901-Methylimidazole2×HCID 343679-Fluorenylmethyl chloroformate2×HCID 10688060HCID 10688060, compound

Product 1

HCID 10674302HCID 10674302, compoundYield 89.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 9-fluorenylmethyl chloroformate (97%, 270 mg, 1.01 mmol) in dry CH2Cl2 (20 mL) was treated with 1-methylimidazole (90 mg, 1.10 mmol), followed by the above amine (270 mg, 0.84 mmol). The mixture was stirred at 20° C. for 1.5 h, then treated with additional 1-methylimidazole (18 mg, 0.22 mmol) and 9-fluorenylmethyl chloroformate (54 mg, 0.20 mmol). The mixture was stirred for a further 3 h and was then concentrated under reduced pressure, and the residue was chromatographed on silica gel. Elution with CH2Cl2 /petroleum ether (9:1) gave a solid that was recrysallized from iPr2O/petroleum ether to give give 3-(tert-butyloxycarbonyl)-1-(chloromethyl)-5-(9-fluorenylmethyloxycarbonylamino)-1,2-dihydro-3H-benz[e]indole (417 mg, 89%), mp 103-106° C. 1H NMR [(CD3)2SO] δ 9.73 (s, 1 H, NHCO2), 8.21 (br s, 1 H, H-4), 7.98 (d, J=8.5 Hz, 1 H, ArH), 7.95-7.85 (m, 3 H, ArH), 7.76 (br s, 2 H, ArH), 7.54 (t, J=7.5 Hz, 1 H, ArH), 7.48-7.27 (m, 5 H, ArH), 4.46 (d, J=7.0 Hz, 2 H, aliphatic H), 4.32 (t, J=6.8 Hz, 1 H, aliphatic H), 4.26-4.11 (m, 2 H, aliphatic H), 4.11-3.97 (m, 2 H, CHHCl, aliphatic H), 3.88 (dd, J=10.7, 6.9 Hz, 1 H, CHHCl), 1.52 (s, 9 H, C(CH3)3).

Workup

  1. stirringThe mixture was stirred for a further 3 h
  2. concentrationwas then concentrated under reduced pressure
  3. customthe residue was chromatographed on silica gel
  4. washElution with CH2Cl2 /petroleum ether (9:1)
  5. customgave a solid
  6. customto give

Sources & evidence

ORD record
ord-bd882119409e46e485e5c82673ac2c6a
Source dataset
uspto-grants-2000_10
Patent number
US06130237

Reaction notes

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