Ethanesulfonylchloride, 2-chloro- → HCID 66698109, compound

HRID 1256518Notes

Reaction equation

HRID 1256518 reaction equation
[F:1][CH:2]([F:33])[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]([O:20][CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[N:9]=2)[C:6]2[CH:27]=[CH:28][CH:29]=[C:30]([O:31][CH3:32])[C:5]=2[N:4]=1.CCN(C(C)C)C(C)C.Cl[CH2:44][CH2:45][S:46](Cl)(=[O:48])=[O:47]>C(Cl)Cl.O>[F:33][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]([O:20][CH:21]3[CH2:26][CH2:25][N:24]([S:46]([CH:45]=[CH2:44])(=[O:48])=[O:47])[CH2:23][CH2:22]3)[N:9]=2)[C:6]2[CH:27]=[CH:28][CH:29]=[C:30]([O:31][CH3:32])[C:5]=2[N:4]=1

Participants

6

Reactant 3

HCID 15385Ethanesulfonylchloride, 2-chloro-HCID 81531DiisopropylethylamineHCID 67535565HCID 67535565, compound

Product 1

HCID 66698109HCID 66698109, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(4-piperidinyloxy)-1,3,5-triazin-2-yl]-1H-benzimidazole (Example 16) (1.52 g, 3.29 mmol) and DIPEA (2.3 ml, 4 eq.) in CH2Cl2 (30 mL) at 0° C. was added 2-chloroethanesulfonyl chloride (1 mL, excess). The reaction mixture was stirred at 20° C. for 20 hrs and diluted with water (50 mL). The CH2Cl2 layer was separated and the aqueous layer was further extracted with CH2Cl2 (3×20 mL). The combined organic fractions were washed successively with aq. HOAc, aq. K2CO3, and water, and dried (MgSO4). Evaporation of the solvent and chromatography of the residue on silica, eluting with CH2Cl2/EtOAc (9:1) gave 2-(difluoromethyl)-4-methoxy-1-(4-(4-morpholinyl)-6-{[1-(vinylsulfonyl)-4-piperidinyl]oxy}-1,3,5-triazin-2-yl)-1H-benzimidazole (1.17 g, 65% yield): mp (CH2Cl2/MeOH) 266-269° C.; 1H NMR (DMSO-d6) δ7.95 (d, J=7.9 Hz, 1H), 7.70 (t, JHF=52.8 Hz, 1H), 7.44 (t, J=8.2 Hz, 1H), 6.98 (d, J=7.8 Hz, 1H), 6.88 (dd, J=16.5, 10.0 Hz, 1H), 6.19 (d, J=10.0 Hz, 1H), 6.15 (d, J=16.5 Hz, 1H), 5.26-5.20 (m, 1H), 3.98 (s, 3H), 3.84 (m, 4H), 3.74-3.32 (m, 4H), 3.39-3.32 (m, 2H), 3.14-3.08 (m, 2H), 2.14-2.09 (m, 2H), 1.90-1.18 (m, 2H); Anal. Calcd. for C23H27F2N7O5S.0.5CH2Cl2: C, 47.7; H, 4.7; N, 16.5. Found: C, 47.8; H, 4.7; N, 16.8%.

Workup

  1. customThe CH2Cl2 layer was separated
  2. extractionthe aqueous layer was further extracted with CH2Cl2 (3×20 mL)
  3. washThe combined organic fractions were washed successively with aq. HOAc, aq. K2CO3, and water
  4. dry with materialdried (MgSO4)
  5. customEvaporation of the solvent and chromatography of the residue on silica
  6. washeluting with CH2Cl2/EtOAc (9:1)

Sources & evidence

ORD record
ord-8c227a5c5ba1464cb542feccee3c3e53
Source dataset
uspto-grants-2013_06
Patent number
US08461158B2

Reaction notes

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