Triethylamine → (S)-3-((E)-2-{3-Benzyloxy-4-[1,1,4-trioxo-5-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-2-yl]-phenyl}-vinyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic Acid Tert-butyl Ester

HRID 660662Notes

Reaction equation

HRID 660662 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13](I)[CH:12]=[CH:11][C:10]=1[N:16]1[S:20](=[O:22])(=[O:21])[N:19]([CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:18](=[O:29])[CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:30]([O:34][C:35]([N:37]1[C@H:46]([CH:47]=[CH2:48])[CH2:45][C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31].CCN(CC)CC.C(C1C=CC(C2C=CC=CC=2)=C(P)C=1C(C)(C)C)(C)(C)C>C(#N)C.Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:30]([O:34][C:35]([N:37]1[C@H:46](/[CH:47]=[CH:48]/[C:13]2[CH:12]=[CH:11][C:10]([N:16]3[CH2:17][C:18](=[O:29])[N:19]([CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[S:20]3(=[O:22])=[O:21])=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:14]=2)[CH2:45][C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 21864676Di-t-butyl-phosphinobiphenylHCID 667569375-(2-Benzyloxy-4-iodophenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-oneHCID 68838676(S)-3-Vinyl-3,4-dihydro-1H-isoquinoline-2-carboxylic Acid Tert-butyl Ester

Product 1

HCID 68996827(S)-3-((E)-2-{3-Benzyloxy-4-[1,1,4-trioxo-5-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-2-yl]-phenyl}-vinyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic Acid Tert-butyl Ester

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 313Hydrochloric AcidSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one (0.77 g, 1.4 mmol) and (S)-3-vinyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (0.44 g, 1.7 mmol) in acetonitrile (5 mL) in a pressure vessel is added Et3N (0.32 mL, 2.3 mmol) followed by di-t-butyl-phosphinobiphenyl (0.017 g, 0.057 mmol). The solution is degassed by nitrogen sparging for 10 min, and then Pd(OAc)2 (0.006 g, 0.028 mmol) is added and the mixture is heated to 80° C. for 18 h. The mixture is cooled to RT and is diluted with 1N HCl and extracted with EtOAc (2×30 mL). The organic layer is washed with brine (3×30 mL) and dried over Na2SO4. The solvent is removed under reduced pressure and the residue purified by flash chromatography using a gradient of 5 to 30% EtOAc in hexanes to give the title compound.

Workup

  1. customThe solution is degassed by nitrogen sparging for 10 min
  2. temperatureThe mixture is cooled to RT
  3. extractionextracted with EtOAc (2×30 mL)
  4. washThe organic layer is washed with brine (3×30 mL)
  5. dry with materialdried over Na2SO4
  6. customThe solvent is removed under reduced pressure
  7. customthe residue purified by flash chromatography

Sources & evidence

ORD record
ord-f9bda00b05cc4bf7a7c90c1c267a46cf
Source dataset
uspto-grants-2011_12
Patent number
US08084448B2

Reaction notes

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