Triethylamine → N-[3(R)-5-Cyclohexyl-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]N'[4-methyl-3-(methylsulphonylaminocarbonyl)phenyl]urea

HRID 2379358Notes

Reaction equation

HRID 2379358 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[C:9]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[O:10].ClC(Cl)(O[C:20](=[O:26])OC(Cl)(Cl)Cl)Cl.C(N([CH2:33][CH3:34])CC)C.[NH2:35][C@@H:36]1[N:42]=[C:41](C2CCCCC2)[C:40]2[CH:49]=[CH:50][CH:51]=[CH:52][C:39]=2[N:38]([CH3:53])[C:37]1=[O:54]>O1CCCC1>[CH2:34]1[CH2:33][CH:4]([C@@:36]2([NH:35][C:20]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([C:9]([NH:11][S:12]([CH3:15])(=[O:14])=[O:13])=[O:10])[CH:4]=3)=[O:26])[N:42]=[CH:41][C:40]3[CH:49]=[CH:50][CH:51]=[CH:52][C:39]=3[N:38]([CH3:53])[C:37]2=[O:54])[CH2:3][CH2:2][CH2:1]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 18656025HCID 18656025, compoundHCID 189577552-Methyl-1-(methylsulphonylaminocarbonyl)-5-aminobenzene

Product 1

HCID 67821678N-[3(R)-5-Cyclohexyl-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]N'[4-methyl-3-(methylsulphonylaminocarbonyl)phenyl]ureaYield 95.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The title compound was prepared in the same way as that described in Example 33, Step 4, using 2-methyl-1-(methylsulphonylaminocarbonyl)-5-aminobenzene (185 mg, 0.81 mmol), triphosgene (80 mg, 0.27 mmol), triethylamine (0.34 ml, 2.42 mmol), 3(R)-amino-5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (0.15 g, 0.56 mmol) and tetrahydrofuran (25 ml). After recrystallisation from methanol, the title compound (135 mg, 46%) was afforded as a colourless solid with >99% e.e. mp 175° C. (dec.). 1H NMR (360 MHz, D6DMSO) δ 1.00-1.41 (4H, m), 1.51-1.71 (4H, m), 1.80-1.86 (1H, m), 1.96-2.04 (1H, m), 2.35 (3H, s), 2.79-2.88 (1H, m), 3.31 (3H, s), 3.40 (3H, s), 5.26 (1H, d, J= 7.5 Hz), 7.08 (1H, d, J=8.3 Hz), 7.30-7.42 (4H, m), 7.54-7.65 (3H, m), 8.94 (1H, s), 11.86 (1H, s). [α]D -7.7° (c=0.44, CH3OH).

Workup

  1. customThe title compound was prepared in the same way as
  2. customAfter recrystallisation from methanol

Sources & evidence

ORD record
ord-a7c706e7b16d4b67a68429fce8f33076
Source dataset
uspto-grants-1994_11
Patent number
US05360802

Reaction notes

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