Triethylamine → 4-(2-((1-(5-fluoropyrimidin-2-yl)piperidin-4-yl)oxy)benzo[d]thiazol-6-yl)-N,N-dimethyl-5,6-dihydropyridine-1(2H)-sulfonamide

HRID 1429585Notes

Reaction equation

HRID 1429585 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([O:14][C:15]3[S:16][C:17]4[CH:23]=[C:22]([C:24]5[CH2:25][CH2:26][NH:27][CH2:28][CH:29]=5)[CH:21]=[CH:20][C:18]=4[N:19]=3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C(N(CC)CC)C.[CH3:37][N:38]([CH3:43])[S:39](Cl)(=[O:41])=[O:40]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([O:14][C:15]3[S:16][C:17]4[CH:23]=[C:22]([C:24]5[CH2:25][CH2:26][N:27]([S:39]([N:38]([CH3:43])[CH3:37])(=[O:41])=[O:40])[CH2:28][CH:29]=5)[CH:21]=[CH:20][C:18]=4[N:19]=3)[CH2:10][CH2:9]2)=[N:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 83372Dimethylsulphamoyl chlorideHCID 674681792-(1-(5-Fluoropyrimidin-2-yl)piperidin-4-yloxy)-6-(1,2,3,6-tetrahydropyridin-4-yl)benzo[d]thiazole

Product 1

HCID 545968874-(2-((1-(5-fluoropyrimidin-2-yl)piperidin-4-yl)oxy)benzo[d]thiazol-6-yl)-N,N-dimethyl-5,6-dihydropyridine-1(2H)-sulfonamideYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-((1-(5-fluoropyrimidin-2-yl)piperidin-4-yl)oxy)-6-(1,2,3,6-tetrahydropyridin-4-yl)benzo[d]thiazole (20 mg, 0.049 mmol) and triethylamine (0.014 mL, 0.097 mmol) in CH2Cl2 (0.7 mL) at 0° C. was added dimethylsulfamoyl chloride (17.4 mg, 0.122 mmol). The reaction mixture was stirred at 0° C. for 15 min, then at rt for 3 h. The reaction mixture was quenched with sat. aq. NaHCO3 (1 mL) and extracted with CH2Cl2 (3×1 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The crude product was purified by column chromatography (silica gel, CH2Cl2-EtOAc gradient 0 to 40% EtOAc) to afford 4-(2-((1-(5-fluoropyrimidin-2-yl)piperidin-4-yl)oxy)benzo[d]thiazol-6-yl)-N,N-dimethyl-5,6-dihydropyridine-1(2H)-sulfonamide (15 mg, 0.027 mmol, 57% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.20 (s, 2H), 7.64 (d, J=1.7 Hz, 1H), 7.62 (d, J=8.5 Hz, 1H), 7.40 (dd, J=8.5, 1.9 Hz, 1H), 6.07 (dt, J=3.2, 1.8 Hz, 1H), 5.45 (tt, J=7.7, 3.7 Hz, 1H), 4.17 (ddd, J=13.4, 7.2, 3.9 Hz, 2H), 3.98-3.92 (m, 2H), 3.70 (ddd, J=13.4, 8.3, 3.6 Hz, 2H), 3.52 (t, J=5.6 Hz, 2H), 2.86 (s, 6H), 2.69-2.61 (m, 2H), 2.21-2.12 (m, 2H), 2.00-1.88 (m, 2H). LCMS (m/z)=519 (M+H)+.

Workup

  1. waitat rt for 3 h
  2. customThe reaction mixture was quenched with sat. aq. NaHCO3 (1 mL)
  3. extractionextracted with CH2Cl2 (3×1 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (silica gel, CH2Cl2-EtOAc gradient 0 to 40% EtOAc)

Sources & evidence

ORD record
ord-55bb0586ede240c4afdad80561dca601
Source dataset
uspto-grants-2015_01
Patent number
US08940716B2

Reaction notes

Loading…