Water → HCID 178481559, compound

HRID 2223068Notes

Reaction equation

HRID 2223068 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH:9]([NH:14][C:15]([NH:19][C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[C:23]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[CH:22][CH:21]=3)=[N:16][C:17]#[N:18])[N:8]=[C:7]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[Cl:42])[C:6]=2[CH:43]=1.O.FC(F)(F)C(O)=[O:48]>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH:9]([NH:14]/[C:15](/[NH:19][C:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[C:23]([N:30]4[CH2:31][CH2:32][O:33][CH2:34][CH2:35]4)=[CH:22][CH:21]=3)=[N:16]/[C:17]([NH2:18])=[O:48])[N:8]=[C:7]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[Cl:42])[C:6]=2[CH:43]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 178481558HCID 178481558, compound

Product 1

HCID 178481559HCID 178481559, compoundYield 40.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of N-[7-chloro-5-(2-chlorophenyl)-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-N″-cyano-N′-[4-(4-morpholinyl)-1-naphthalenyl]guanidine (EXAMPLE 10) (21.9 mg, 35.8 μmol), water (4.6 μL, 260 μmol) and trifluoroacetic acid (19.8 μL, 257 μmol) in THF (3 mL) was heated to reflux for 43 h. The reaction was concentrated in vacuo, and the residue was purified by reverse phase HPLC (gradient 20-70% CH3CN in H2O) to provide the title compound (0.0092 g, 35%) as its TFA salt. 1H-NMR (CD3OD): δ 8.37 (br s, 1H), 8.06 (br s, 1H), 7.75-7.41 (br m, 9H), 7.26 (br s, 1H), 7.04 (br s, 1H), 5.66 (br s, 1H), 4.00 (br s, 4H), 3.58 (br s, 3H), 3.17 (br s, 4H). HRMS calculated for (C32H29Cl2N7O3+H) (M+H)+: 630.1787. Found (ESI): 630.1800.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 43 h
  3. concentrationThe reaction was concentrated in vacuo
  4. customthe residue was purified by reverse phase HPLC (gradient 20-70% CH3CN in H2O)

Sources & evidence

ORD record
ord-58662a94b1c64084a8bc0370490d7185
Source dataset
uspto-grants-2008_05
Patent number
US07375101B2

Reaction notes

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