Cesium carbonate → HCID 67980492, compound

HRID 1622309Notes

Reaction equation

HRID 1622309 reaction equation
[C:1]([C:4]1([CH3:17])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)(=[O:3])[NH2:2].Br[C:19]1[CH:39]=[CH:38][C:22]([CH2:23][N:24]2[CH2:33][CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[C:29]([C:34]([O:36][CH3:37])=[O:35])[CH:30]=3)[CH2:25]2)=[CH:21][CH:20]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:13]([O:12][C:10]([N:7]1[CH2:8][CH2:9][C:4]([C:1]([NH:2][C:19]2[CH:39]=[CH:38][C:22]([CH2:23][N:24]3[CH2:33][CH2:32][C:31]4[C:26](=[CH:27][CH:28]=[C:29]([C:34]([O:36][CH3:37])=[O:35])[CH:30]=4)[CH2:25]3)=[CH:21][CH:20]=2)=[O:3])([CH3:17])[CH2:5][CH2:6]1)=[O:11])([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 53393793tert-Butyl 4-carbamoyl-4-methylpiperidine-1-carboxylateHCID 67980521HCID 67980521, compound

Product 1

HCID 67980492HCID 67980492, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl 4-carbamoyl-4-methylpiperidine-1-carboxylate (178 mg, 0.733 mmol), methyl 2-(4-bromobenzyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxylate (240 mg, 0.670 mmol), Pd2(dba)3 (61 mg, 0.066 mmol), Xantphos (116 mg, 0.200 mmol), and Cs2CO3 (434 mg, 1.33 mmol) in dioxane (10.6 mL) was degassed thoroughly and the reaction vessel was sealed. The mixture was heated at 100° C. overnight and then filtered. The filtrate was concentrated. The resulting residue was purified by column chromatography (SiO2, 0-90% EtOAc in hexane) to give methyl 2-[4-({[1-(tert-butoxycarbonyl)-4-methylpiperidin-4-yl]carbonyl}amino)benzyl]-1,2,3,4-tetrahydroisoquinoline-6-carboxylate (160 mg, 46%). LC-MS: (FA) ES+ 522; 1H NMR (400 MHz, CDCl3) δ 7.78 (s, 1H), 7.75 (dd, J=8.0, 1.6 Hz, 1H), 7.48 (d, J=8.5 Hz, 2H), 7.33 (dd, J=9.3, 7.0 Hz, 3H), 7.01 (t, J=7.3 Hz, 1H), 3.91-3.83 (m, 3H), 3.67 (dd, J=19.7, 4.9 Hz, 5H), 3.40-3.27 (m, 2H), 3.00-2.85 (m, 2H), 2.73 (t, J=5.9 Hz, 2H), 2.13-1.96 (m, 3H), 1.55 (t, J=21.0 Hz, 2H), 1.46 (d, J=5.0 Hz, 9H), 1.31 (d, J=9.9 Hz, 3H).

Workup

  1. customwas degassed thoroughly
  2. customthe reaction vessel was sealed
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. customThe resulting residue was purified by column chromatography (SiO2, 0-90% EtOAc in hexane)

Sources & evidence

ORD record
ord-be4499c3baff4acc884421bfc373ca52
Source dataset
uspto-grants-2014_07
Patent number
US08778931B2

Reaction notes

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