Thionyl Chloride → HCID 178522090, compound

HRID 2223370Notes

Reaction equation

HRID 2223370 reaction equation
S(Cl)(Cl)=O.[NH2:5][C:6]1[C:7]([C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][N:20]=2)=[O:17])=[CH:8][C:9]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[CH:11][CH:10]=2.[O:26]=[C:27]1[CH2:31][CH2:30][CH2:29][N:28]1[C@H:32]1[CH2:37][CH2:36][C@H:35]([C:38](O)=[O:39])[CH2:34][CH2:33]1.Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.CN(C)C=O.CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[Cl:25][C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:16]([C:7]2[C:6]([NH:5][C:38]([C@H:35]3[CH2:36][CH2:37][C@H:32]([N:28]4[CH2:29][CH2:30][CH2:31][C:27]4=[O:26])[CH2:33][CH2:34]3)=[O:39])=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]=2)=[O:17])=[N:20][CH:21]=1

Participants

10

Reactant 5

HCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 231250193-amino-N-(5-chloropyridin-2-yl)-2-naphthamideHCID 178516220HCID 178516220, compound

Product 1

HCID 178522090HCID 178522090, compoundYield 70.4%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 6212ChloroformSolvent

Procedure

Trans-4-(2-oxopyrrolidin-1-yl)cyclohexane-carboxylic acid (40 mg) obtained in Reference Example 2 is dissolved in chloroform (3 ml), and thereto are added thionyl chloride (15 μl) and N,N-dimethylformamide (1 drop) followed by stirring at room temperature for 15 hours. To the reaction solution are added 3-amino-N-(5-chloropyridin-2-yl)-2-naphthamide (31 mg) obtained in Example 34(1) and pyridine (1 ml), and the mixture is stirred at room temperature for 12 hours. After adding trans-4-(2-oxopyrrolidin-1-yl)cyclohexanecarboxylic acid (43 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (42 mg) and 4-(dimethylamino)pyridine (56 mg), the mixture is stirred at room temperature for another 12 hours. To the reaction solution is poured saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with chloroform. The extract is dried over sodium sulfate and evaporated to remove the solvent under reduced pressure. The resulting residue is purified by NH-silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/1, then 1/4) to give title compound (36 mg).

Workup

  1. stirringthe mixture is stirred at room temperature for 12 hours
  2. stirringthe mixture is stirred at room temperature for another 12 hours
  3. extractionthe mixture is extracted with chloroform
  4. dry with materialThe extract is dried over sodium sulfate
  5. customevaporated
  6. customto remove the solvent under reduced pressure
  7. customThe resulting residue is purified by NH-silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-7a60568a9b0a411e85c391df41237b67
Source dataset
uspto-grants-2008_05
Patent number
US07375119B2

Reaction notes

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