Triethylamine → Methyl 3-Cyano-2-[(2-{[(2S)-2-(3,4-dichlorophenyl)pent-4-enyl]amino}ethyl)thio]-1-naphthoate Hydrochloride

HRID 1760952Notes

Reaction equation

HRID 1760952 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][S:5][C:6]1[C:15]([C:16]#[N:17])=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]=1[C:18]([O:20][CH3:21])=[O:19].C(N(CC)CC)C.[Cl:29][C:30]1[CH:31]=[C:32]([C@H:37]([CH2:40][CH:41]=[CH2:42])[CH:38]=O)[CH:33]=[CH:34][C:35]=1[Cl:36].C([BH3-])#N.[Na+].C([O-])([O-])=O.[K+].[K+]>CO.C(Cl)Cl.C(O)(=O)C>[ClH:29].[C:16]([C:15]1[C:6]([S:5][CH2:4][CH2:3][NH:2][CH2:38][C@H:37]([C:32]2[CH:33]=[CH:34][C:35]([Cl:36])=[C:30]([Cl:29])[CH:31]=2)[CH2:40][CH:41]=[CH2:42])=[C:7]([C:18]([O:20][CH3:21])=[O:19])[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)#[N:17]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 5003444Sodium cyanoborohydrideHCID 15261880(2S)-2-(3,4-dichlorophenyl)pent-4-enalHCID 22593652Methyl 2-[(2-aminoethyl)thio]-3-cyano-1-naphthoate hydrochloride2×

Product 1

HCID 69138873Methyl 3-Cyano-2-[(2-{[(2S)-2-(3,4-dichlorophenyl)pent-4-enyl]amino}ethyl)thio]-1-naphthoate Hydrochloride

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl 2-[(2-aminoethyl)thio]-3-cyano-1-naphthoate hydrochloride (Intermediate 3, 530 mg, 1.65 mmol) in methanol (100 mL) was added triethylamine (250 μL, 1.82 mmol). After 30 min (2S)-2-(3,4-dichlorophenyl)pent-4-enal {Intermediate 4, 525 mg (72% pure), 1.65 mmol} and the pH was adjusted to 4-5 with acetic acid. After 30 min a solution of sodium cyanoborohydride (200 mg, 3.20 mmol) in methanol (2 mL) was added and reaction mixture stirred at ambient temperature overnight. Reaction mixture volume reduced by half and 20% K2CO3 (50 mL) was added. Reaction mixture volume reduced further to about 50 mL and methylene chloride (100 mL) was added. The organic layer was washed with brine, dried (Na2SO4), and evaporated to an oil which was chromatography on silica gel in 5% MeOH/CHCl3 to give 730 mg of the free base. The free base was dissolved in HCl/MeOH and evaporated to dryness to give 780 mg of the title compound.

Workup

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  3. additionwas added
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  6. washThe organic layer was washed with brine
  7. dry with materialdried (Na2SO4)
  8. customevaporated to an oil which

Sources & evidence

ORD record
ord-45c2aa06f5a541b3b82924d01f90bd04
Source dataset
uspto-grants-2005_01
Patent number
US06846814B2

Reaction notes

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