2-(Tributylstannyl)furan → (R)-2-(2-(2,4-Dimethoxybenzyl)-7-fluoro-4-(furan-2-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanamide

HRID 711573

Reaction equation

HRID 711573 reaction equation
Cl[C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4]([NH:24][C@H:25]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:26]([NH2:28])=[O:27])[N:3]=1.C([Sn](CCCC)(CCCC)[C:38]1[O:39][CH:40]=[CH:41][CH:42]=1)CCC>C1(C)C=CC=CC=1.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>[CH3:21][O:20][C:13]1[CH:14]=[C:15]([O:18][CH3:19])[CH:16]=[CH:17][C:12]=1[CH2:11][N:9]1[CH2:10][C:6]2[C:5]([F:23])=[C:4]([NH:24][C@H:25]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:26]([NH2:28])=[O:27])[N:3]=[C:2]([C:38]3[O:39][CH:40]=[CH:41][CH:42]=3)[C:7]=2[C:8]1=[O:22]

Participants

5

Reactant 2

HCID 43936882-(Tributylstannyl)furanHCID 58317560(R)-2-(4-Chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanamide

Product 1

HCID 58317552(R)-2-(2-(2,4-Dimethoxybenzyl)-7-fluoro-4-(furan-2-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanamideYield 58%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

A solution of (R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)-4-methylpentanamide (150 mg, 0.323 mmol), tributyl(furan-2-yl)stannane (138 mg, 0.387 mmol), and tetrakis(triphenylphosphine)palladium(0) (373 mg, 0.323 mmol) in toluene (1 mL) was heated to 102° C. overnight. After removal of the solvent, the residue was diluted in MeOH/DCM (10 mL) and was purified via preparative HPLC eluting with water (0.05% TFA) and ACN (45-60% gradient, 0.035% TFA). The collected fractions were stripped to dryness via rotary evaporation to give the title compound (93.1 mg, 58%). [M+H] calc'd for C26H29FN4O5, 498. found 498.

Workup

  1. customAfter removal of the solvent
  2. additionthe residue was diluted in MeOH/DCM (10 mL)
  3. customwas purified via preparative HPLC
  4. washeluting with water (0.05% TFA) and ACN (45-60% gradient, 0.035% TFA)
  5. customThe collected fractions were stripped to dryness via rotary evaporation

Sources & evidence

ORD record
ord-ff95b0dd02564effad30138028bdadc5
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Linked notes

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