Diisopropylethylamine → 2-[(2S)-2-(3,4-Dichlorophenyl)pent-4-enyl]-1-oxo-1,2,3,4-tetrahydronaphtho[1,2-f][1,4]thiazepine-6-carbonitrile

HRID 1767457Notes

Reaction equation

HRID 1767457 reaction equation
[C:1]([C:3]1[C:4]([S:16][CH2:17][CH2:18][NH:19][CH2:20][C@H:21]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=2)[CH2:22][CH:23]=[CH2:24])=[C:5]([C:13]([OH:15])=O)[C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2)#[N:2].C(N(C(C)C)CC)(C)C.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1>C(#N)C.C(OCC)(=O)C>[Cl:32][C:27]1[CH:26]=[C:25]([C@H:21]([CH2:22][CH:23]=[CH2:24])[CH2:20][N:19]2[C:13](=[O:15])[C:5]3[C:6]4[C:11]([CH:12]=[C:3]([C:1]#[N:2])[C:4]=3[S:16][CH2:17][CH2:18]2)=[CH:10][CH:9]=[CH:8][CH:7]=4)[CH:30]=[CH:29][C:28]=1[Cl:31]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 599794983-cyano-2-[(2-{[(2S)-2-(3,4-Dichlorophenyl)pent-4-enyl]amino}ethyl)thio]-1-naphthoic acid2×

Product 1

HCID 98046052-[(2S)-2-(3,4-Dichlorophenyl)pent-4-enyl]-1-oxo-1,2,3,4-tetrahydronaphtho[1,2-f][1,4]thiazepine-6-carbonitrileYield 26.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-cyano-2-[(2-{[(2S)-2-(3,4-Dichlorophenyl)pent-4-enyl]amino}ethyl)thio]-1-naphthoic acid (Intermediate 6, 135 mg, 0.28 mmol) in dry acetonitrile (6 mL) under nitrogen at 0° C. was added diisopropylethyl amine (146 μL, 0.84 mmol) and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl, 86 mg, 0.34 mmol). Stirring was continued for 45 min as the reaction mixture was allowed to warm to ambient temperature. The reaction mixture was diluted with ethyl acetate (50 mL), washed with 0.5 N HCl and brine, dried (Na2SO4), and evaporated to a residue which was chromatographed on silica gel in 25–40% EtOAc/Hexanes to give 85 mg of partially purified material. A portion (50 mg) of this material was chromatographed on silica gel in 20% EtOAc/Hexanes to give 35 mg of the title compound.

Workup

  1. washwashed with 0.5 N HCl and brine
  2. dry with materialdried (Na2SO4)
  3. customevaporated to a residue which
  4. customwas chromatographed on silica gel in 25–40% EtOAc/Hexanes
  5. customto give 85 mg of partially purified material
  6. customA portion (50 mg) of this material was chromatographed on silica gel in 20% EtOAc/Hexanes

Sources & evidence

ORD record
ord-8f167077110e43919d0fcb2550bf0cb7
Source dataset
uspto-grants-2007_06
Patent number
US07235541B2

Reaction notes

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