Potassium Carbonate → benzyl 4-((R)-2-((6-(2-cyanophenyl)-2-(2-(tetrahydro-2H-pyran-2-yl)ethylamino)nicotinamido)methyl)pyrrolidin-1-yl)-4-oxobutylcarbamate

HRID 2080304Notes

Reaction equation

HRID 2080304 reaction equation
Cl[C:2]1[CH:32]=[CH:31][C:5]([C:6]([NH:8][CH2:9][C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15](=[O:30])[CH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:29])[O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:7])=[C:4]([NH:33][CH2:34][CH2:35][CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][O:37]2)[N:3]=1.[C:42]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1B(O)O)#[N:43].C([O-])([O-])=O.[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C>[C:42]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1[C:2]1[CH:32]=[CH:31][C:5]([C:6]([NH:8][CH2:9][C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15](=[O:30])[CH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:29])[O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:7])=[C:4]([NH:33][CH2:34][CH2:35][CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][O:37]2)[N:3]=1)#[N:43]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27346102-Cyanophenylboronic acidHCID 57542717benzyl 4-((R)-2-((6-chloro-2-(2-(tetrahydro-2H-pyran-2-yl)ethylamino)nicotinamido)methyl)pyrrolidin-1-yl)-4-oxobutylcarbamate

Product 1

HCID 57542296benzyl 4-((R)-2-((6-(2-cyanophenyl)-2-(2-(tetrahydro-2H-pyran-2-yl)ethylamino)nicotinamido)methyl)pyrrolidin-1-yl)-4-oxobutylcarbamateYield 77%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of benzyl 4-((R)-2-((6-chloro-2-(2-(tetrahydro-2H-pyran-2-yl)ethylamino)nicotinamido)methyl)pyrrolidin-1-yl)-4-oxobutylcarbamate (62 mg, 0.101 mmol), 2-cyanophenyl boronic acid (23 mg, 0.156 mmol), PdCl2(dppf)2 (11 mg, 0.02 mmol), K2CO3(92 g, 0.667 mmol) and anhydrous DMF (1 mL) was stirred at 125° C. for 1 hr. The mixture was filtered through the silica gel pad and washed with EtOAc. The filtrate was concentrated to dryness and purified on RP-HPLC using a mixture of acetonitrile and H2O to give benzyl 4-((R)-2-((6-(2-cyanophenyl)-2-(2-(tetrahydro-2H-pyran-2-yl)ethylamino)nicotinamido)methyl)pyrrolidin-1-yl)-4-oxobutylcarbamate (50 mg, 77%). LRMS (M+H+) m/z 653.3.

Workup

  1. filtrationThe mixture was filtered through the silica gel pad
  2. washwashed with EtOAc
  3. concentrationThe filtrate was concentrated to dryness
  4. custompurified on RP-HPLC
  5. additiona mixture of acetonitrile and H2O

Sources & evidence

ORD record
ord-aaf6166adf3a44ac8f4513283245a134
Source dataset
uspto-grants-2011_04
Patent number
US07932270B2

Reaction notes

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