5-Bromo-N-methoxy-N-methylpyridine-3-carboxamide → (5-Bromo-pyridin-3-yl)-{7-[1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-methanone

HRID 82277Notes

Reaction equation

HRID 82277 reaction equation
I[C:2]1[C:10]2[CH:9]=[N:8][CH:7]=[N:6][C:5]=2[N:4]([C:11]2([CH2:14][O:15][CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][O:17]3)[CH2:13][CH2:12]2)[CH:3]=1.C([Li])CCC.[Br:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32]([CH:39]=1)[C:33](N(OC)C)=[O:34]>C(OCC)C>[Br:27][C:28]1[CH:39]=[C:32]([C:33]([C:2]2[C:10]3[CH:9]=[N:8][CH:7]=[N:6][C:5]=3[N:4]([C:11]3([CH2:14][O:15][CH:16]4[CH2:21][CH2:20][CH2:19][CH2:18][O:17]4)[CH2:13][CH2:12]3)[CH:3]=2)=[O:34])[CH:31]=[N:30][CH:29]=1

Participants

5

Reactant 3

HCID 184722695-Bromo-N-methoxy-N-methylpyridine-3-carboxamideHCID 708172755-Iodo-7-[1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropyl]-7H-pyrrolo[2,3-d]pyrimidineHCID 178418339Butyllithium

Product 1

HCID 70817567(5-Bromo-pyridin-3-yl)-{7-[1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-methanoneYield 35%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a stirred solution of 5-Iodo-7-[1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropyl]-7H-pyrrolo[2,3-d]pyrimidine (Preparation 249, 450 mg, 1.13 mmol) in diethyl ether (6 mL) was added n-butyl lithium (2M in hexane, 0.62 mL, 1.24 mmol) drop wise at −70° C. Then a solution of 5-Bromo-N-methoxy-N-methyl-nicotinamide (304 mg, 1.24 mmol) in diethyl ether (2.5 mL) was added drop wise at −70° C. and stirred at same temperature for another 30 minutes. The reaction was allowed to warm to room temperature slowly. The reaction was quenched with saturated aqueous ammonium chloride solution (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layer was washed with water (20 mL), brine (20 mL), dried over sodium sulphate and evaporated in vacuo. The crude material was purified by column chromatography on silica gel (gradient of dichloromethane:methanol 100:0 to 98:2) to afford the title compound as a light brown sticky solid in 35% yield, 250 mg.

Workup

  1. customThe reaction was quenched with saturated aqueous ammonium chloride solution (10 mL)
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. washThe combined organic layer was washed with water (20 mL), brine (20 mL)
  4. dry with materialdried over sodium sulphate
  5. customevaporated in vacuo
  6. customThe crude material was purified by column chromatography on silica gel (gradient of dichloromethane:methanol 100:0 to 98:2)

Sources & evidence

ORD record
ord-e7b2cf3c951840488e96c71fbe7fb596
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Reaction notes

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