Sodium Carbonate → N-(3-[5-(cyclopropylmethyl-carbamoyl)-pyridin-2-yl]-4-methyl-phenyl)-2-pyrrolidin-1-yl-isonicotinamide

HRID 889337Notes

Reaction equation

HRID 889337 reaction equation
Cl[C:2]1[CH:14]=[CH:13][C:5]([C:6]([NH:8][CH2:9][CH:10]2[CH2:12][CH2:11]2)=[O:7])=[CH:4][N:3]=1.[CH3:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:35])[C:24]2[CH:29]=[CH:28][N:27]=[C:26]([N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)[CH:25]=2)=[CH:18][C:17]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:10]1([CH2:9][NH:8][C:6]([C:5]2[CH:13]=[CH:14][C:2]([C:17]3[CH:18]=[C:19]([NH:22][C:23](=[O:35])[C:24]4[CH:29]=[CH:28][N:27]=[C:26]([N:30]5[CH2:31][CH2:32][CH2:33][CH2:34]5)[CH:25]=4)[CH:20]=[CH:21][C:16]=3[CH3:15])=[N:3][CH:4]=2)=[O:7])[CH2:12][CH2:11]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 11258289N-[4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]-2-pyrrolidin-1-yl-isonicotinamide2×HCID 112758456-chloro-N-(cyclopropylmethyl)pyridine-3-carboxamide2×

Product 1

HCID 9933726N-(3-[5-(cyclopropylmethyl-carbamoyl)-pyridin-2-yl]-4-methyl-phenyl)-2-pyrrolidin-1-yl-isonicotinamideYield 59.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

6-Chloro-N-cyclopropylmethylnicotinamide (Intermediate 1) (25 mg, 0.098 mmol) and N-[4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-2-pyrrolidin-1yl-isonicotinamide (Intermediate 18) (30 mg, 0.074 mmol), aqueous sodium carbonate (2N, 0.5 ml) and tetrakis(triphenylphosphine)palladium (4 mg) were heated at 80° C. in DMF (1 ml) for 18 hours. The reaction was absorbed onto silica,applied to a bond-elut (10 g, silica) and eluted with an ethylacetate/cyclohexane (0 to 100%), then acetone and methanol. The solvent was evaporated from the product fractions under vacuum and the residue triturated with ether to give N-(3-[5-(cyclopropylmethyl-carbamoyl)-pyridin-2-yl]-4-methyl-phenyl)-2-pyrrolidin-1-yl-isonicotinamide as a white solid (20 mg). LCMS: retention time 2.42 min, MH+ 456. NMR: δH [2H6]-DMSO 10.32,(1H, s), 9.09,(1H, s), 8.82,(1H, t), 8.28,(1H, m), 8.19,(1H, m), 7.85,(1H, t), 7.76,(1H, m), 7.64,(1H, m), 7.31,(1H, m), 6.98,(1H, m), 6.88,(1H, s), 3.43,(4H, m), 3.18,(2H, m), 2.31,(3H, s), 1.95,(4H, m), 1.07,(1H, m), 0.45,(2H, m), 0.25,(2H, m).

Workup

  1. customThe reaction was absorbed onto silica,applied to a bond-elut (10 g, silica)
  2. washeluted with an ethylacetate/cyclohexane (0 to 100%)
  3. customThe solvent was evaporated from the product fractions under vacuum
  4. customthe residue triturated with ether

Sources & evidence

ORD record
ord-71a56a7b447248b9b0d08aa76a2ea52f
Source dataset
uspto-grants-2012_08
Patent number
US08252818B2

Reaction notes

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