2-Amino-5-methylpyridine → HCID 90041616, compound

HRID 522948Notes

Reaction equation

HRID 522948 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.Br[C:10]1[N:11]=[C:12]2[C:18]([C:19]([NH:21][C:22]([CH3:26])([CH3:25])[CH2:23][OH:24])=[O:20])=[CH:17][N:16]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:13]2=[N:14][CH:15]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1.CN(C=O)C>[OH:24][CH2:23][C:22]([NH:21][C:19]([C:18]1[C:12]2[C:13](=[N:14][CH:15]=[C:10]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=3)[N:11]=2)[N:16]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:33])([CH3:32])[CH3:34])[CH:17]=1)=[O:20])([CH3:25])[CH3:26]

Participants

9

Reactant 4

HCID 153482-Amino-5-methylpyridineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 715756472-Bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 90041616HCID 90041616, compoundYield 32%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a mixture of 5-methylpyridin-2-amine (72.1 mg, 666 μmol), 2-bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (197 mg, 444 μmol), (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (13.8 mg, 22.2 μmol), palladium(II) acetate (24.9 mg, 111 μmol) and sodium tert-butoxide (107 mg, 1.11 mmol) was added DMF (2 mL) and toluene (1 mL) then heated in a microwave at 140° C. for 20 min. The dark mixture generated was poured into water and extracted with ethyl acetate (3×). The organic layers were combined, washed with brine (2×), dried over magnesium sulfate and purified by chromatography (silica, 65-100% ethyl acetate in hexanes) to give N-(1-hydroxy-2-methylpropan-2-yl)-2-(5-methylpyridin-2-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (66 mg, 140 μmol, 32%) as a light yellow solid. MS (EI/CI) m/z: 471.4.

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washwashed with brine (2×)
  3. dry with materialdried over magnesium sulfate
  4. custompurified by chromatography (silica, 65-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-aa4f7ea3769d49ed9b97ba525828b141
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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