Tetrahydrofuran → N-(2-chloro-5-(2-(methylamino)benzo[d]thiazol-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide

HRID 2077613Notes

Reaction equation

HRID 2077613 reaction equation
[CH3:1][NH:2][C:3]1[S:4][C:5]2[CH:11]=[C:10](B3OC(C)(C)C(C)(C)O3)[CH:9]=[CH:8][C:6]=2[N:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:28]1[CH:29]=[C:30]([NH:35][S:36]([C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=2)(=[O:38])=[O:37])[C:31]([Cl:34])=[N:32][CH:33]=1.C1COCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[Cl:34][C:31]1[C:30]([NH:35][S:36]([C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=2)(=[O:38])=[O:37])=[CH:29][C:28]([C:10]2[CH:9]=[CH:8][C:6]3[N:7]=[C:3]([NH:2][CH3:1])[S:4][C:5]=3[CH:11]=2)=[CH:33][N:32]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 53363354N-(5-bromo-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamideHCID 58279591N-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-amine

Product 1

HCID 57585117N-(2-chloro-5-(2-(methylamino)benzo[d]thiazol-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamideYield 21.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Procedure

To a microwave vial equipped with a stirbar and charged with N-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-amine (0.22 g, 0.75 mmol), cesium carbonate (0.67 g, 2.1 mmol), PdCl2(dppf)*DCM (0.10 g, 0.12 mmol), N-(5-bromo-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide (0.250 g, 0.68 mmol) was added THF (3 ml). Then water (0.5 ml) was added into the mixture. The vial was capped and then placed into a CEM Microwave for 10 minutes at 100° C., while 100 watts of energy was supplied via Powermax® (Simultaneous heating while cooling technology). The progress of the reaction was monitored by LC/MS, which showed desired material in the mixture. The organic layer was extracted from the microwave vial by pipet and then diluted the organic with acetonitrile (15 ml) and TFA (0.1 ml). The crude was purified by reverse-phase HPLC. This gave N-(2-chloro-5-(2-(methylamino)benzo[d]thiazol-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide (0.065 g, 21% yield) as a yellow crystalline solid. MS (ESI pos. ion) m/z: 449 (MH+). Calc'd exact mass for C19H14ClFN4O2S2: 448. 1H NMR (400 MHz, DMSO-d6): 2.97 (d, J=3.51 Hz, 3H), 7.42 (t, J=8.78 Hz, 2H), 7.46-7.53 (m, 2H), 7.81 (dd, J=8.53, 5.02 Hz, 2H), 7.94 (s, 1H), 8.03 (s, 1H), 8.13 (d, J=4.02 Hz, 1H), 8.54 (s, 1H), 10.45 (s, 1H).

Workup

  1. customTo a microwave vial equipped with a stirbar
  2. customThe vial was capped
  3. temperaturewas supplied via Powermax® (Simultaneous heating while cooling technology)
  4. extractionThe organic layer was extracted from the microwave vial by pipet
  5. additiondiluted the organic with acetonitrile (15 ml) and TFA (0.1 ml)
  6. customThe crude was purified by reverse-phase HPLC

Sources & evidence

ORD record
ord-1d114f40017d4af3baef12bd3b2050db
Source dataset
uspto-grants-2011_04
Patent number
US07928140B2

Reaction notes

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