3-Aminopyridine → HCID 90040937, compound

HRID 522996Notes

Reaction equation

HRID 522996 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:18])([CH3:17])[CH2:15][OH:16])=[O:12])=[CH:9][N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:5]2=[N:6][CH:7]=1.[N:27]1[CH:32]=[CH:31][CH:30]=[C:29]([NH2:33])[CH:28]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].ClCCl.CO>[OH:16][CH2:15][C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([NH:33][C:29]3[CH:28]=[N:27][CH:32]=[CH:31][CH:30]=3)[N:3]=2)[N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:9]=1)=[O:12])([CH3:18])[CH3:17]

Participants

8

Reactant 4

HCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 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 90040937HCID 90040937, compoundYield 18%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2-bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (150 mg, 338 μmol), pyridin-3-amine (47.8 mg, 507 μmol), xantphos (58.7 mg, 101 μmol), Pd2(dba)3 (31.0 mg, 33.8 μmol) and cesium carbonate (220 mg, 677 μmol) in dioxane (2 mL) was heated in a microwave at 150° C. for 20 min. The mixture was cooled then filtered through a pad of celite. The filtrate was concentrated in vacuo then purified by chromatography (silica, 40-100% ethyl acetate in hexanes gradient then dichloromethane/methanol) to give N-(1-hydroxy-2-methylpropan-2-yl)-2-(pyridin-3-ylamino)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (32 mg, 59.6 μmol, 18%) as a light yellow solid. (EI/CI) m/z: 472.3 [M+H].

Workup

  1. temperatureThe mixture was cooled
  2. filtrationthen filtered through a pad of celite
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthen purified by chromatography (silica, 40-100% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-c92178c6981148998c343ad11a73c83c
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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