Diisopropylethylamine → HCID 46918268, compound

HRID 516367Notes

Reaction equation

HRID 516367 reaction equation
[F:1][CH:2]([F:32])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([N:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[C:29]([O:30][CH3:31])[C:5]=2[N:4]=1.Cl.Cl.[CH3:35][N:36]([CH3:49])[CH2:37][CH2:38][CH2:39][S:40](N1CCNCC1)(=[O:42])=[O:41].CCN(C(C)C)C(C)C>CS(C)=O.O>[F:32][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:11]=[C:10]([N:20]3[CH2:25][CH2:24][N:23]([S:40]([CH2:39][CH2:38][CH2:37][N:36]([CH3:49])[CH3:35])(=[O:42])=[O:41])[CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[C:29]([O:30][CH3:31])[C:5]=2[N:4]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 666980472-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazoleHCID 67545767HCID 67545767, compound

Product 1

HCID 46918268HCID 46918268, compoundYield 40.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

A mixture of 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (Example 2) (150 mg, 0.378 mmol), N,N-dimethyl-3-(1-piperazinylsulfonyl)-1-propanamine dihydrochloride (WO 2006/046040) (151 mg, 0.491 mmol), and DIPEA (0.40 mL, 2.27 mmol) in DMSO was stirred at room temperature for 30 minutes. The reaction mixture was diluted with water; and the resulting precipitate was collected by filtration, washed with water, and dissolved in CH2Cl2. The solution was dried (Na2SO4) and the solvent removed under vacuum. Chromatography on silica eluting with CH2Cl2/MeOH (95:5), followed by additional chromatography on silica eluting with CH2Cl2/MeOH (96:4) gave N-[3-({4-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1-piperazinyl}sulfonyl)propyl]-N,N-dimethylamine (91 mg, 40%). Treatment with 1.25 M HCl solution in MeOH and recrystallization from MeOH/EtOAc gave the hydrochloride salt: mp 209-211° C.; 1H NMR (DMSO-d6) δ10.16 (br s, 1H), 7.89 (d, J=8.4 Hz, 1H), 7.69 (t, JHF=52.9 Hz, 1H), 7.41 (t, J=8.2 Hz, 1H), 6.96 (d, J=7.8 Hz, 1H), 3.98 (s, 3H), 3.94 (m, 4H), 3.82 (m, 4H), 3.70 (br s, 4H), 3.33 (m, 4H), 3.23 (dd, J=9.3, 5.8 Hz, 2H), 3.12 (m, 2H), 2.75 (s, 6H), 2.08 (td, J=15.4, 7.8 Hz, 2H); Anal. Calcd. for C25H36ClF2N9O4S.0.5H2O: C, 46.8; H, 5.8; N, 19.7. Found: C, 46.9; H, 5.8; N, 19.4%.

Workup

  1. filtrationand the resulting precipitate was collected by filtration
  2. washwashed with water
  3. dissolutiondissolved in CH2Cl2
  4. dry with materialThe solution was dried (Na2SO4)
  5. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-71a812c785864334a1051826651baf3f
Source dataset
uspto-grants-2015_08
Patent number
US09108980B2

Reaction notes

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