2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl → tert-butyl 3-(2-(1,3-dioxolan-2-yl)ethyl)-6-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)picolinate

HRID 1518392Notes

Reaction equation

HRID 1518392 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[N:28]=[C:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:26](Br)=[CH:25][CH:24]=1)[CH2:19][CH2:18]2)=[O:12].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[Br-].[O:67]1[CH2:71][CH2:70][O:69][CH:68]1[CH2:72][CH2:73][Zn+]>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:67]1[CH2:71][CH2:70][O:69][CH:68]1[CH2:72][CH2:73][C:26]1[C:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[N:28][C:23]([N:20]2[CH2:19][CH2:18][C:17]3[C:22](=[C:13]([C:11](=[O:12])[NH:10][C:2]4[S:1][C:5]5[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=5[N:3]=4)[CH:14]=[CH:15][CH:16]=3)[CH2:21]2)=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 594476151,1-Dimethylethyl 6-(8-((2-benzothiazolylamino)carbonyl)-3,4-dihydro-2(1H)-isoquinolinyl)-3-bromo-2-pyridinecarboxylateHCID 178419780HCID 178419780, compound

Product 1

HCID 59447567tert-butyl 3-(2-(1,3-dioxolan-2-yl)ethyl)-6-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)picolinateYield 91.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of compound 94B (8.0 g, 14.15 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (1.162 g, 2.83 mmol) and palladium acetate (0.318 g, 1.415 mmol) in THF (60 mL) was stirred at room temperature for 5 min. To this solution was added 0.5 M (2-(1,3-dioxolan-2-yl)ethyl)zinc(II) bromide (56.6 mL, 28.3 mmol) via an additional funnel drop wise at room temperature. The reaction was stirred overnight. The solvent was removed, and residue was loaded on a silica column and eluted with 7:3/hexanes: EtOAc to give 7.58 g of desired product 96A: APCI (+)LC/MS: 587 (M+H)+.

Workup

  1. stirringThe reaction was stirred overnight
  2. customThe solvent was removed
  3. washeluted with 7:3/hexanes

Sources & evidence

ORD record
ord-94d41a642a0c446e83d129abf1c80005
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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