Cesium carbonate → HCID 67980849, compound

HRID 2406221Notes

Reaction equation

HRID 2406221 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[N:11]([C:12](Br)=[N:13][N:14]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:19]1([CH2:25][CH2:26][C@@H:27]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([S:43]([NH2:46])(=[O:45])=[O:44])=[CH:39][C:38]=2[S:47]([C:50]([F:53])([F:52])[F:51])(=[O:49])=[O:48])[CH2:28][S:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.CN[C@H]1CCCC[C@@H]1NC.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu]I.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[N:11]([C:12]([NH:46][S:43]([C:40]3[CH:41]=[CH:42][C:37]([NH:36][C@@H:27]([CH2:28][S:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH2:26][CH2:25][N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[C:38]([S:47]([C:50]([F:52])([F:53])[F:51])(=[O:49])=[O:48])[CH:39]=3)(=[O:44])=[O:45])=[N:13][N:14]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 13822957(1S,2S)-(+)-N,N'-Dimethylcyclohexane-1,2-diamineHCID 250584544-[[(1R)-3-(4-Morpholinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoromethyl)sulfonyl]benzenesulfonamideHCID 67980981HCID 67980981, compound

Product 1

HCID 67980849HCID 67980849, compoundYield 44.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

3-Bromo-4,5,7,8-tetrahydro-1,2,3a,6-tetraaza-azulene-6-carboxylic acid tert-butyl ester (154 mg, 0.486 mmol), 4-((R)-3-morpholin-4-yl-1-phenylsulfanylmethyl-propylamino)-3-trifluoromethane sulfonyl-benzenesulfonamide (269 mg, 0.486 mmol), (1S,2S)—N,N′-dimethyl-cyclohexane-1,2-diamine (0.011 mL, 0.146 mmol), cesium carbonate (269 mg, 0.825 mmol), and copper (I) iodide (13.87 mg, 0.073 mmol) were added to a microwave vial followed by toluene (8 mL). The reaction mixture was degassed for 15 minutes under nitrogen, sealed, and then heated conventionally to 90° C. for 14 hours. The crude material was directly purified via flash chromatography on silica gel (0-15% 2N NH3 in methanol in CH2Cl2) to afford the title compound (170 mg, 44% yield). MS [m/z; (M+1)+]: 790.5

Workup

  1. customThe reaction mixture was degassed for 15 minutes under nitrogen
  2. customsealed
  3. customThe crude material was directly purified via flash chromatography on silica gel (0-15% 2N NH3 in methanol in CH2Cl2)

Sources & evidence

ORD record
ord-5cbc3d8d676d402a94ab9908c270c48a
Source dataset
uspto-grants-2014_08
Patent number
US08809352B2

Reaction notes

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