Dimethylamine → HCID 46918202, compound

HRID 1619834Notes

Reaction equation

HRID 1619834 reaction equation
[F:1][CH:2]([F:41])[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][CH:23]([N:26]([CH2:31][CH2:32][CH2:33]O)[S:27]([CH3:30])(=[O:29])=[O:28])[CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:35]=[CH:36][CH:37]=[C:38]([O:39][CH3:40])[C:5]=2[N:4]=1.C[CH2:43][N:44](CC)[CH2:45]C.CS(Cl)(=O)=O.CNC>C(Cl)Cl>[NH3:4].[F:41][CH:2]([F:1])[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[CH2:25][CH2:24][CH:23]([N:26]([CH2:31][CH2:32][CH2:33][N:44]([CH3:45])[CH3:43])[S:27]([CH3:30])(=[O:28])=[O:29])[CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:35]=[CH:36][CH:37]=[C:38]([O:39][CH3:40])[C:5]=2[N:4]=1

Participants

7

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 66698086HCID 66698086, compound

Product 2

HCID 222AmmoniaHCID 46918202HCID 46918202, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The above alcohol (305 mg, 0.51 mmol) in CH2Cl2 (15 mL) was treated with Et3N (0.3 mL) and methanesulfonyl chloride (0.2 mL, 2.5 mmol) at 0° C. The reaction mixture was stirred at this temp for 45 min and 40% aqueous solution of dimethylamine (5 mL) was then added. Stirring was continued for 2 days at 20° C., and the CH2Cl2 was evaporated. The residue was diluted with water, and the resulting precipitate was washed with water and dried. Chromatography on neutral alumina, eluting with CH2Cl2/MeOH (98:2), followed by chromatography on silica, eluting with CH2Cl2/MeOH/aq. NH3 (96:3:1) gave 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 (200 mg, 63%). The amine was converted to the hydrochloride salt by combining with 1.25 M HCl in MeOH. Recrystallization from MeOH/isopropanol gave 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 hydrochloride: mp 187-191° C.; 1H NMR (DMSO-d6) δ 9.83 (br s, 1H), 7.89 (d, J=8.0 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), 4.84-4.73 (m, 2H), 3.98 (s, 3H), 3.92-3.85 (m, 1H), 3.80 (m, 4H), 3.70 (m, 4H), 3.16 (t, J=7.4 Hz, 2H), 3.11-2.96 (m, 7H), 2.71 (s, 6H), 1.91-1.83 (m, 4H), 1.73-1.68 (m, 2H); Anal. Calcd. for C27H40ClF2N9O4S.H2O: C, 47.8; H, 6.2; N, 18.6; Cl, 5.2. Found: C, 47.9; H, 6.2; N, 18.6; Cl, 5.0%.

Workup

  1. stirringStirring
  2. waitwas continued for 2 days at 20° C.
  3. customthe CH2Cl2 was evaporated
  4. additionThe residue was diluted with water
  5. washthe resulting precipitate was washed with water
  6. customdried
  7. washChromatography on neutral alumina, eluting with CH2Cl2/MeOH (98:2)
  8. washeluting with CH2Cl2/MeOH/aq

Sources & evidence

ORD record
ord-d9df0b5164d143508e81d61c78e7c853
Source dataset
uspto-grants-2014_07
Patent number
US08772287B2

Reaction notes

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