Diisopropylethylamine → 1-[4-[2-(Difluoromethyl)-4-methoxy-1h-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-n-[2-(dimethylamino)ethyl]-4-piperidinesulfonamide

HRID 516407Notes

Reaction equation

HRID 516407 reaction equation
[CH3:1][N:2]([CH3:25])[CH2:3][CH2:4][NH:5][S:6]([CH:9]1[CH2:14][CH2:13][N:12]([C:15](OCC2C=CC=CC=2)=O)[CH2:11][CH2:10]1)(=[O:8])=[O:7].ClC1[N:32]=[C:31]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)[N:30]=[C:29]([N:39]2[C:43]3[CH:44]=[CH:45][CH:46]=[C:47]([O:48][CH3:49])[C:42]=3[N:41]=[C:40]2[CH:50]([F:52])[F:51])[N:28]=1.CCN(C(C)C)C(C)C>CO.C1COCC1.[Pd]>[F:52][CH:50]([F:51])[C:40]1[N:39]([C:29]2[N:30]=[C:31]([N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)[N:32]=[C:15]([N:12]3[CH2:11][CH2:10][CH:9]([S:6]([NH:5][CH2:4][CH2:3][N:2]([CH3:1])[CH3:25])(=[O:7])=[O:8])[CH2:14][CH2:13]3)[N:28]=2)[C:43]2[CH:44]=[CH:45][CH:46]=[C:47]([O:48][CH3:49])[C:42]=2[N:41]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 534881021-[4-Chloro-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazoleHCID 66698082Benzyl 4-({[2-(dimethylamino)ethyl]amino}sulfonyl)-1-piperidinecarboxylate

Product 1

HCID 469175761-[4-[2-(Difluoromethyl)-4-methoxy-1h-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-n-[2-(dimethylamino)ethyl]-4-piperidinesulfonamide

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

The above carbamate was hydrogenated over 5% Pd on carbon in MeOH. After removal of the solvent, the residue was combined with 0.48 g (1.2 mmol) 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (Example 2) and 0.35 g (2.7 mmol) DIPEA in THF. The mixture was heated under reflux for 1 hr and the solvent was concentrated. After dilution with water, the resulting solid was collected and dried. Chromatography on alumina, eluting with EtOAc, gave 1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-N-[2-(dimethylamino)ethyl]-4-piperidinesulfonamide: mp (MeOH) 231-234° C.; 1H NMR (CDCl3) δ 7.87 (dd, J=8.4, 0.6 Hz, 1H), 7.47 (t, JHF=53.5 Hz, 1H), 7.35 (t, J=8.2 Hz, 1H), 6.81 (d, J=7.8 Hz, 1H), 4.91 (br d, J=13.3 Hz, 2H), 4.04 (s, 3H), 3.88 (m, 4H), 3.78 (m, 4H), 3.25-3.17 (m, 3H), 3.00 (m, 2H), 2.45 (br t, J=5.7 Hz, 2H), 2.27 (m, 2H), 2.23 (s, 6H), 1.83 (dq, J=12.5, 4.4 Hz, 2H); Anal. Calcd. for C25H35F2N9O4S: C, 50.4; H, 5.9; N, 21.2. Found: C, 50.2; H, 5.7; N, 21.3%.

Workup

  1. customAfter removal of the solvent
  2. temperatureThe mixture was heated
  3. temperatureunder reflux for 1 hr
  4. concentrationthe solvent was concentrated
  5. customAfter dilution with water, the resulting solid was collected
  6. customdried
  7. washChromatography on alumina, eluting with EtOAc

Sources & evidence

ORD record
ord-652e202d24ad4ae8a2dd32aaf0283b45
Source dataset
uspto-grants-2015_08
Patent number
US09108980B2

Reaction notes

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