Triethylamine → HCID 67796126, compound

HRID 1655009Notes

Reaction equation

HRID 1655009 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9](=[O:14])[NH:10][CH2:11][C:12]=2[OH:13])[CH:5]=[CH:6][CH:7]=1.C(N([CH2:20][CH3:21])CC)C.ClC(Cl)(O[C:26](=[O:32])OC(Cl)(Cl)Cl)Cl.[NH2:34][C@@H:35]1[N:41]=[C:40](C2CCCCC2)[C:39]2[CH:48]=[CH:49][CH:50]=[CH:51][C:38]=2[N:37]([CH3:52])[C:36]1=[O:53]>O1CCCC1>[CH2:21]1[CH2:20][CH:6]([C@@:35]2([NH:34][C:26]([NH:1][C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([C:8]4[C:9](=[O:14])[NH:10][CH2:11][C:12]=4[OH:13])[CH:3]=3)=[O:32])[N:41]=[CH:40][C:39]3[CH:48]=[CH:49][CH:50]=[CH:51][C:38]=3[N:37]([CH3:52])[C:36]2=[O:53])[CH2:7][CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 94429TriphosgeneHCID 18656025HCID 18656025, compoundHCID 547073163-(3-Aminophenyl)-1,5-dihydro-4-hydroxy-2H-pyrrol-2-one

Product 1

HCID 67796126HCID 67796126, compoundYield 40.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

3-(3-Aminophenyl)-1,5-dihydro-4-hydroxy-2H-pyrrol-2-one (409 mg, 2.15 mmol) was suspended in anhydrous tetrahydrofuran (40 ml), under an atmosphere of nitrogen. Triethylamine (296 μl, 2.14 mmol) was then added dropwise over rain and the mixture stirred for a further 2 min. The mixture was then cooled to 0° C. and triphosgene (210 mg, 0.71 mmol) was added and the mixture stirred for 2 min. Triethylamine (595 μl, 4.3 mmol) was then added over a 5 min period and the mixture stirred at 0° C. for a further 5 min. The cooling bath was removed and the mixture stirred at ambient temperature for 10 min. The mixture was then cooled back to 0° C. and a solution of (R)-amino-5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (400 mg, 1.47 mmol) in anhydrous tetrahydrofuran (5 ml) was added dropwise. The mixture was stirred at 0° C. for 5 rain then allowed to warm to room temperature and stirred for 30 min. The residue was then evaporated in vacuo and the residue chromatographed on silica gel, using 94:6:0.6 dichloromethane:methanol:acetic acid as the eluant. The title compound (140 mg, 20%) was isolated as a white solid. mp 220° C. (dec.). 1H NMR (360MHz, D6 -DMSO) δ0.90 (1H, m), 1.09-1.91 (9H, m), 2.93 (1H, m), 3.32 (3H, s), 3.82 (2H, s), 5.07 (1H, d, J=8Hz), 7.13 (1H, t, J=8Hz), 7.23 (1H, d, J =8Hz), 7.35-7.39 (2H, m), 7.53-7.65 (3H, m), 7.74 (1H, d, J=8Hz), 7.85 (1H, s), 8.97 (1H, s).

Workup

  1. stirringthe mixture stirred for 2 min
  2. stirringthe mixture stirred at 0° C. for a further 5 min
  3. customThe cooling bath was removed
  4. stirringthe mixture stirred at ambient temperature for 10 min
  5. temperatureThe mixture was then cooled back to 0° C.
  6. stirringThe mixture was stirred at 0° C. for 5 rain
  7. temperatureto warm to room temperature
  8. stirringstirred for 30 min
  9. customThe residue was then evaporated in vacuo
  10. customthe residue chromatographed on silica gel

Sources & evidence

ORD record
ord-e24a1a9ea3864c02a98d69d7a911e67d
Source dataset
uspto-grants-1995_04
Patent number
US05410049

Reaction notes

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