Ethanesulfonylchloride, 2-chloro- → HCID 66698074, compound

HRID 1619784Notes

Reaction equation

HRID 1619784 reaction equation
[F:1][CH:2]([F:32])[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]([CH: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][CH3:31])[C:5]=2[N:4]=1.CCN(C(C)C)C(C)C.Cl[CH2:43][CH2:44][S:45](Cl)(=[O:47])=[O:46].C(Cl)Cl.CCOC(C)=O>C(Cl)Cl>[F:32][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]([CH:20]3[CH2:21][CH2:22][N:23]([S:45]([CH:44]=[CH2:43])(=[O:47])=[O:46])[CH2:24][CH2:25]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[C:29]([O:30][CH3:31])[C:5]=2[N:4]=1

Participants

6

Reactant 4

HCID 15385Ethanesulfonylchloride, 2-chloro-HCID 81531DiisopropylethylamineHCID 21226138Dichloromethane ethylacetateHCID 66698078HCID 66698078, compound

Product 1

HCID 66698074HCID 66698074, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(4-piperidinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (Example 13) (0.891 mg, 2 mmol) and DIPEA (0.77 g, 6 mmol) in CH2Cl2 (100 mL) was added dropwise 2-chloroethanesulfonyl chloride (0.49 g, 3 mmol) at 0° C. After addition, the reaction mixture was stirred at 0° C. for additional 2 hrs. The reaction mixture was quenched with water (100 mL). The organic layer was washed successively with aqueous HOAc (1%, 100 mL) and aqueous NH3, and dried. Chromatography on silica eluting with CH2Cl2/EtOAc (9:1) gave 0.589 g (55% yield) of 2-(difluoromethyl)-4-methoxy-1-{4-(4-morpholinyl)-6-[1-(vinylsulfonyl)-4-piperidinyl]-1,3,5-triazin-2-yl}-1H-benzimidazole: mp (MeOH) 229-232° C.; 1H NMR (CDCl3) δ 7.99 (dd, J=8.4, 0.7 Hz, 1H), 7.54 (t, JHF=53.6 Hz, 1H), 7.39 (t, J=8.3 Hz, 1H), 6.85 (d, J=7.6 Hz, 1H), 6.47 (dd, J=16.6, 9.9 Hz, 1H), 6.27 (d, J=16.6 Hz, 1H), 6.05 (d, J=9.9 Hz, 1H), 4.06 (s, 3H), 4.00-3.97 (m, 4H), 3.89-3.79 (m, 6H), 2.78 (m, 3H), 2.17 (br dd, J=13.6, 3.0 Hz, 2H), 2.01 (ddd, J=25.2, 11.7, 4.1 Hz, 2H); Anal. Calcd. for C23H27F2N7O4S: C, 51.6; H, 5.1; N, 18.3. Found: C, 51.7; H, 5.2; N, 18.25%.

Workup

  1. additionAfter addition
  2. customThe reaction mixture was quenched with water (100 mL)
  3. washThe organic layer was washed successively with aqueous HOAc (1%, 100 mL) and aqueous NH3
  4. customdried

Sources & evidence

ORD record
ord-89c613f9a38f44778f9d6486751aaa05
Source dataset
uspto-grants-2014_07
Patent number
US08772287B2

Reaction notes

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