Diisopropylethylamine → HCID 46917496, compound

HRID 516372Notes

Reaction equation

HRID 516372 reaction equation
[Cl:1][CH2:2][S:3]([N:6]([CH2:13][CH2:14][CH2:15][N:16]([CH3:18])[CH3:17])[CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)(=[O:5])=[O:4].[F:19][CH:20]([F:50])[C:21]1[N:25]([C:26]2[N:31]=[C:30]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[N:29]=[C:28](N3CCNCC3)[N:27]=2)[C:24]2[CH:44]=[CH:45][CH:46]=[C:47]([O:48][CH3:49])[C:23]=2[N:22]=1.CCN(C(C)C)C(C)C.C(Cl)Cl.CO>C1COCC1>[Cl:1][CH2:2][S:3]([N:6]([CH:7]1[CH2:12][CH2:11][N:10]([C:28]2[N:27]=[C:26]([N:25]3[C:24]4[CH:44]=[CH:45][CH:46]=[C:47]([O:48][CH3:49])[C:23]=4[N:22]=[C:21]3[CH:20]([F:50])[F:19])[N:31]=[C:30]([N:32]3[CH2:33][CH2:34][O:35][CH2:36][CH2:37]3)[N:29]=2)[CH2:9][CH2:8]1)[CH2:13][CH2:14][CH2:15][N:16]([CH3:17])[CH3:18])(=[O:4])=[O:5]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 21226129Dichloromethane methanolHCID 666980472-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazoleHCID 66698092HCID 66698092, compound

Product 1

HCID 46917496HCID 46917496, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of the above amine (82 mg, 0.28 mmol), 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (Example 2) (98 mg, 0.25 mmol), and DIPEA (0.3 mL) in THF (5 mL) was stirred at 20° C. for 4 hrs. Most of the THF was removed under vacuum and the residue was diluted with water (20 mL). The resulting precipitate was collected by filtration, washed with water, and chromatographed on silica eluting initially with CH2Cl2/EtOAc (4:1), then with CH2Cl2/MeOH/aqueous NH3 (95:4:1) to give chloro-N-{1-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-4-piperidinyl}-N-[3-(dimethylamino)propyl]methanesulfonamide (120 mg 74% yield), which treated with 1.25 M HCl in MeOH to give the hydrochloride salt: mp (MeOH/EtOAc) 260-263° C.; 1H NMR (DMSO-d6) δ10.0 (br s, 1H), 7.89 (d, J=8.2 Hz, 1H), 7.70 (t, JHF=52.9 Hz, 1H), 7.41 (t, J=8.2 Hz, 1H), 6.95 (d, J=7.9 Hz, 1H), 5.10 (s, 2H), 4.86-4.74 (m, 2H), 3.98-3.90 (m, 1H), 3.98 (s, 3H), 3.81 (m, 4H), 3.79 (m, 4H), 3.24-3.25 (m, 2H), 3.11-2.96 (m, 4H), 2.70 (s, 6H), 1.93-1.75 (m, 6H); Calcd. for C27H39Cl2F2N9O4S.0.5H2O: C, 46.1; H, 5.7; N, 17.9; Cl, 10.1. Found: C, 46.1; H, 5.8; N, 17.9; Cl, 9.7%.

Workup

  1. customMost of the THF was removed under vacuum
  2. additionthe residue was diluted with water (20 mL)
  3. filtrationThe resulting precipitate was collected by filtration
  4. washwashed with water
  5. customchromatographed on silica eluting initially with CH2Cl2/EtOAc (4:1)

Sources & evidence

ORD record
ord-03168103a5444a37a151d691e97c6f21
Source dataset
uspto-grants-2015_08
Patent number
US09108980B2

Reaction notes

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