Ethyl Acetate → HCID 46917498, compound

HRID 1619762Notes

Reaction equation

HRID 1619762 reaction equation
[F:1][CH:2]([F:37])[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][NH:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[C:29]([O:30][CH2:31][CH2:32][CH2:33][N:34]([CH3:36])[CH3:35])[C:5]=2[N:4]=1.C([O-])([O-])=O.[K+].[K+].[CH3:44][S:45](Cl)(=[O:47])=[O:46].CCOC(C)=O>C(Cl)Cl.O>[F:37][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:9]=[C:10]([N:20]3[CH2:25][CH2:24][N:23]([S:45]([CH3:44])(=[O:47])=[O:46])[CH2:22][CH2:21]3)[N:11]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:13]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[C:29]([O:30][CH2:31][CH2:32][CH2:33][N:34]([CH3:36])[CH3:35])[C:5]=2[N:4]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 66698096HCID 66698096, compound

Product 1

HCID 46917498HCID 46917498, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A stirred mixture of 297 mg (0.57 mmol) of N-[3-({2-(difluoromethyl)-1-[4-(4-morpholinyl)-6-(1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazol-4-yl}oxy)propyl]-N,N-dimethylamine and 1 g of powdered K2CO3 in CH2Cl2 was cooled to 0° C. and 0.4 g of methanesulphonyl chloride was added. The mixture was allowed to warm to room temperature, and after 2 hrs it was diluted with water and the organic layer was separated and dried. Chromatography on alumina, eluting first with CH2Cl2/EtOAc (1:1) and then with EtOAc gave 200 mg (59% yield) of N-[3-({2-(difluoromethyl)-1-[4-[4-(methylsulfonyl)-1-piperazinyl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazol-4-yl}oxy)propyl]-N,N-dimethylamine: 1H NMR (CDCl3) δ 7.84 (dd, J=8.4. 0.6 Hz, 1H), 7.43 (t, JHF=53.5 Hz, 1H), 7.33 (t, J=8.2 Hz, 1H), 6.86 (d, J=7.7 Hz, 1H), 4.32 (t, J=6.8 Hz, 2H), 4.02 (m, 4H), 3.88 (m, 4H), 3.78 (m, 4H), 3.33 (m, 4H), 2.81 (s, 3H), 2.54 (t, J=7.2 Hz, 2H), 2.28 (s, 6H), 2.14 (pentet, J=7.0 Hz, 2H); Hydrochloride: mp (EtOH) 243-247° C.; Anal. Calcd. for C25H36ClF2N9O4S.1.5H2O: C, 45.6; H, 6.0; Cl, 5.4, N, 19.1. Found: C, 45.5; H, 6.1; Cl, 5.2; N, 19.2%.

Workup

  1. temperatureto warm to room temperature
  2. customthe organic layer was separated
  3. customdried
  4. washChromatography on alumina, eluting first with CH2Cl2/EtOAc (1:1)

Sources & evidence

ORD record
ord-32410e6211624480aec01b413ed362a7
Source dataset
uspto-grants-2014_07
Patent number
US08772287B2

Reaction notes

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