Diisopropylethylamine → HCID 67545781, compound

HRID 1619796Notes

Reaction equation

HRID 1619796 reaction equation
[OH:1][CH2:2][CH2:3][CH2:4][NH:5][CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]1.Cl[C:20]1[N:25]=[C:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[N:23]=[C:22]([N:32]2[C:36]3[CH:37]=[CH:38][CH:39]=[C:40]([O:41][CH3:42])[C:35]=3[N:34]=[C:33]2[CH:43]([F:45])[F:44])[N:21]=1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[F:45][CH:43]([F:44])[C:33]1[N:32]([C:22]2[N:23]=[C:24]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[N:25]=[C:20]([N:5]([CH2:4][CH2:3][CH2:2][OH:1])[CH:6]3[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]3)[N:21]=2)[C:36]2[CH:37]=[CH:38][CH:39]=[C:40]([O:41][CH3:42])[C:35]=2[N:34]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 534881021-[4-Chloro-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazoleHCID 61637468HCID 61637468, compound

Product 1

HCID 67545781HCID 67545781, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of tert-butyl 3-[(3-hydroxypropyl)amino]-1-piperidinecarboxylate (516 mg, 2.00 mmol), 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (610 mg, 1.54 mmol), and DIPEA (1.5 mL, excess) in DMF (20 mL) was stirred at room temperature for 2 days. The reaction mixture was diluted with water and extracted with CH2Cl2 (3×30 mL). The combined extracts were washed with water, dried over Na2SO4, and concentrated. Chromatography of the residue on SiO2 eluting with a gradient of CH2Cl2/EtOAc (0-40%) gave tert-butyl 3-[[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl](3-hydroxypropyl)-amino]-1-piperidinecarboxylate (854 mg, 90%): mp (CH2Cl2/hexanes) 109-191° C.; 1H NMR (DMSO-d6) (rotamers) δ 8.00 and 7.88 (2d, J=8.3, 8.4 Hz, 1H), 7.79 and 7.63 (2t, JHF=53.0 Hz, 1H), 7.40-7.33 (m, 1H), 6.94 (dd, J=8.0, 4.13 Hz, 1H), 4.60-4.48 and 4.29 (m, 2H), 3.98 and 3.97 (2s, 3H), 3.97-3.48 (m, 16H), 2.93-2.88 and 2.66-2.64 (2 m, 2H), 1.99-1.69 (m, 3H), 1.52-1.17 (m, 10H); Anal. Calcd. for C29H40F2N8O5: C, 56.3; H, 6.5; N, 18.1. Found: C, 56.4; H, 6.4; N, 18.1%.

Workup

  1. extractionextracted with CH2Cl2 (3×30 mL)
  2. washThe combined extracts were washed with water
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-8d1b75ab297a492d91bf76a4046652a6
Source dataset
uspto-grants-2014_07
Patent number
US08772287B2

Reaction notes

Loading…