Dimethylamine → HCID 66698080, compound

HRID 1619797Notes

Reaction equation

HRID 1619797 reaction equation
[F:1][CH:2]([F:44])[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]([CH2:34][CH2:35][CH2:36]O)[CH:21]3[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22]3)[N:9]=2)[C:6]2[CH:38]=[CH:39][CH:40]=[C:41]([O:42][CH3:43])[C:5]=2[N:4]=1.C[CH2:46][N:47](CC)[CH2:48]C.CS(Cl)(=O)=O.CNC>C(Cl)Cl>[F:44][CH:2]([F:1])[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]([CH2:34][CH2:35][CH2:36][N:47]([CH3:48])[CH3:46])[CH:21]3[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22]3)[N:9]=2)[C:6]2[CH:38]=[CH:39][CH:40]=[C:41]([O:42][CH3:43])[C:5]=2[N:4]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 67545781HCID 67545781, compound

Product 1

HCID 66698080HCID 66698080, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 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 (420 mg, 0.72 mmol) in CH2Cl2 (12 mL) at 0° C. was added Et3N (0.2 mL, 1.4 mmol) and methanesulfonyl chloride (0.1 mL, 1.08 mmol). The reaction mixture was stirred at 0° C. for 30 min, and a solution of 40% aqueous dimethylamine (5 mL) was then added. The reaction mixture was stirred at room temperature for 2 days and the solvent was removed under vacuum. The residue was diluted with water and stirred for 30 min to give a precipitate, which was collected by filtration, washed with water, and dried. Chromatography on SiO2 eluting first with CH2Cl2/EtOAc (4:1), and then with CH2Cl2/MeOH (95:5) containing 1% aqueous NH3, gave tert-butyl 3-{[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl][3-(dimethylamino)propyl]amino}-1-piperidinecarboxylate (465 mg; 100%) as a white solid: mp (CH2Cl2/MeOH) 133-136° C.; 1H NMR (DMSO-d6) (rotamers) δ 7.96 and 7.88 (2d, J=8.3 Hz, 1H), 7.77 and 7.68 (2t, JHF=53.0, 52.9 Hz, 1H), 7.40-7.34 (m, 1H), 6.96-6.93 (m, 1H), 4.56-4.88 and 4.30-4.27 (2m, 1H), 3.98 and 3.97 (2s, 3H), 3.97-3.49 (m, 13H), 2.93-2.88 and 2.77-2.63 (2m, 2H), 2.35-2.27 (m, 2H), 2.15 and 2.13 (2s, 6H), 1.93-1.71 (m, 4H), 1.48-1.16 (m, 1H), 1.40 (s, 9H); Anal. Calcd. for C31H45F2N9O4C, 57.7; H, 7.0; N, 19.5. Found: C, 57.7; H, 7.1; N, 19.7%.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 2 days
  2. customthe solvent was removed under vacuum
  3. additionThe residue was diluted with water
  4. stirringstirred for 30 min
  5. customto give a precipitate, which
  6. filtrationwas collected by filtration
  7. washwashed with water
  8. customdried
  9. additionChromatography on SiO2 eluting first with CH2Cl2/EtOAc (4:1), and then with CH2Cl2/MeOH (95:5) containing 1% aqueous NH3

Sources & evidence

ORD record
ord-067006c32efc47f981c2e120f3ae9dad
Source dataset
uspto-grants-2014_07
Patent number
US08772287B2

Reaction notes

Loading…