Sodium Carbonate → N-(6-(6-chloro-5-(4-methoxyphenylsulfonamido)pyridin-3-yl)benzo[d]thiazol-2-yl)cyclohexanecarboxamide

HRID 2077602Notes

Reaction equation

HRID 2077602 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Br[C:8]1[CH:9]=[C:10]([NH:15][S:16]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)(=[O:18])=[O:17])[C:11]([Cl:14])=[N:12][CH:13]=1.CC1(C)C(C)(C)OB([C:35]2[CH:52]=[CH:51][C:38]3[N:39]=[C:40]([NH:42][C:43]([CH:45]4[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]4)=[O:44])[S:41][C:37]=3[CH:36]=2)O1>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].C(Cl)Cl.O1CCOCC1>[Cl:14][C:11]1[N:12]=[CH:13][C:8]([C:35]2[CH:52]=[CH:51][C:38]3[N:39]=[C:40]([NH:42][C:43]([CH:45]4[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]4)=[O:44])[S:41][C:37]=3[CH:36]=2)=[CH:9][C:10]=1[NH:15][S:16]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)(=[O:18])=[O:17]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 51355175HCID 51355175, compoundHCID 86628001N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-yl)cyclohexanecarboxamide

Product 1

HCID 57585067N-(6-(6-chloro-5-(4-methoxyphenylsulfonamido)pyridin-3-yl)benzo[d]thiazol-2-yl)cyclohexanecarboxamideYield 22%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A reaction tube was charged with 2.0 M aqeuous sodium carbonate (199 μL, 397 μmol), PdCl2(dppf)-CH2Cl2 (11 mg, 13 μmol), N-(5-bromo-2-chloropyridin-3-yl)-4-methoxybenzenesulfonamide (50 mg, 132 μmol), N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-yl)cyclohexanecarboxamide (77 mg, 199 μmol) and 0.7 mL dioxane. The tube was purged with argon, sealed and the mixture was heated at 90° C. for 3 h. The reaction mixture was concentrated, dissolved in CH2C2Cl2/MeOH, and purified by silica gel chromatography 0-5% MeOH/CH2Cl2 to provide N-(6-(6-chloro-5-(4-methoxyphenylsulfonamido)pyridin-3-yl)benzo[d]thiazol-2-yl)cyclohexanecarboxamide (16 mg, 22% yield) as a white solid. This material contained a single impurity and was further purified by reverse phase chromatography, Gilson, 20-90% gradient of 0.1% TFA/ACN in water over 15 min to provide N-(6-(6-chloro-5-(4-methoxyphenylsulfonamido)pyridin-3-yl)benzo[d]thiazol-2-yl)cyclohexanecarboxamide (16 mg, 22% yield) as a white solid. MS (ESI pos. ion) m/z calc'd for C26H25ClN4O4S2: 557.1/559.1. found 557.0/558.9. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16-1.51 (m, 6H), 1.73-1.83 (m, 2H), 1.83-1.93 (m, 2H), 2.54-2.62 (m, 1H), 3.83 (s, 3H), 7.07-7.15 (m, 2H), 7.65-7.74 (m, 3H), 7.81-7.88 (m, 1H), 7.99 (s, 1H), 8.32 (s, 1H), 8.61 (s, 1H), 10.23 (s, 1H), 12.39 (s, 1H).

Workup

  1. customThe tube was purged with argon
  2. customsealed
  3. concentrationThe reaction mixture was concentrated
  4. dissolutiondissolved in CH2C2Cl2/MeOH
  5. custompurified by silica gel chromatography 0-5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-91d89943d61948f8bff03a7feb8c6c2f
Source dataset
uspto-grants-2011_04
Patent number
US07928140B2

Reaction notes

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