Dimethylamine → HCID 67544027, compound

HRID 1256449Notes

Reaction equation

HRID 1256449 reaction equation
[F:1][CH:2]([F:42])[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][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:33]=[CH:34][CH:35]=[C:36]([O:37][CH2:38][CH2:39][CH2:40]O)[C:5]=2[N:4]=1.C[CH2:44][N:45](CC)[CH2:46]C.CS(Cl)(=O)=O.N(C)C>C1COCC1>[F:1][CH:2]([F:42])[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[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:31])([CH3:32])[CH3:30])=[O:27])[CH2:24][CH2:25]3)[N:9]=2)[C:6]2[CH:33]=[CH:34][CH:35]=[C:36]([O:37][CH2:38][CH2:39][CH2:40][N:45]([CH3:46])[CH3:44])[C:5]=2[N:4]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 66698035HCID 66698035, compound

Product 1

HCID 67544027HCID 67544027, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of tert-butyl 4-[4-[2-(difluoromethyl)-4-(3-hydroxypropoxy)-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1-piperazinecarboxylate from the previous step and 0.34 g (3.3 mmol) of Et3N in 20 mL of THF was cooled to 0° C. and 0.32 g (2.8 mmol) of methanesulfonyl chloride was added dropwise. After 1 hr, 6 g of 40% aqueous Me2NH was added, and the resulting mixture was stirred at room temperature for 36 hrs. The THF was removed under vacuum and the residue was diluted with water and extracted into CH2Cl2. Drying and removal of the solvent gave tert-butyl 4-[4-{2-(difluoromethyl)-4-[3-(dimethylamino)propoxy]-1H-benzimidazol-1-yl}-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1-piperazinecarboxylate as an oil: 1H NMR (CDCl3) δ 7.87 (dd, J=8.4. 0.6 Hz, 1H), δ 7.48 (t, JHF=53.5 Hz, 1H), 7.33 (t, J=8.2 Hz, 1H), 6.85 (d, J=7.8 Hz, 1H), 4.31 (t, J=6.7 Hz, 2H), 3.87 (m, 8H), 3.79 (m, 4H), 3.53 (m, 4H), 2.51 (t, J=7.2 Hz, 2H), 2.26 (s, 6H), 2.13 (pentet, J=7.0 Hz, 2H), 1.50 (s, 9H).

Workup

  1. customThe THF was removed under vacuum
  2. additionthe residue was diluted with water
  3. extractionextracted into CH2Cl2
  4. customDrying
  5. customremoval of the solvent

Sources & evidence

ORD record
ord-cadcb8292d364d4d8a08180ec7988274
Source dataset
uspto-grants-2013_06
Patent number
US08461158B2

Reaction notes

Loading…