Cesium carbonate → N-methyl-6-(1H-pyrrolo[2,3-b]pyridin-5-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine

HRID 715041Notes

Reaction equation

HRID 715041 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[CH:17]=[CH:16][NH:15][C:12]3=[N:13][CH:14]=2)O1.Cl[C:20]1[N:25]=[C:24]([N:26]([CH3:34])[CH2:27][CH:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[CH:23]=[N:22][CH:21]=1.C([O-])([O-])=O.[Cs+].[Cs+].CO.C(Cl)(Cl)Cl>C1(C)C=CC=CC=1.C(O)C.C(Cl)(Cl)Cl.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>[CH3:34][N:26]([CH2:27][CH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)[C:24]1[CH:23]=[N:22][CH:21]=[C:20]([C:9]2[CH:10]=[C:11]3[CH:17]=[CH:16][NH:15][C:12]3=[N:13][CH:14]=2)[N:25]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 21584188Chloroform methanolHCID 242087895-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridineHCID 534103026-Chloro-N-methyl-N-(tetrahydro-2H-pyran-4-ylmethyl)-2-pyrazinamine

Product 1

HCID 66556275N-methyl-6-(1H-pyrrolo[2,3-b]pyridin-5-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 6212ChloroformSolvent

Conditions

Temperature
80 °C

Procedure

A stirred solution of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (124) (100 mg, 0.409 mmol) and 6-chloro-N-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (69) (90 mg, 0.409 mmol) in toluene (8 mL) and ethanol (2 ml) was degassed and purged under nitrogen for 10 min followed by the addition of Cs2CO3 (260 mg, 0.819 mmol, 2.0 eq) and Pd(PPh3)4 (14 mg, 0.022 mmol, 0.03 eq) and the reaction mixture was degassed and purged again for 15 min. The resulting reaction contents were heated at 80° C. overnight under sealed condition. After completion of the reaction the mixture was diluted with chloroform and filtered through Celite and the organic layer was distilled off to get the crude product. The crude was passed through neutral alumina eluting with 1-2% MeOH/CHCl3 to give off white colored solid N-methyl-6-(1H-pyrrolo[2,3-b]pyridin-5-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine 143 in 9 mg quantity. 1H NMR (400 MHz, CDCl3) δ: 9.05 (s, 1H), 8.97 (d, J=1.95, 1H), 8.53 (d, J=1.95, 1H), 8.34 (s, 1H), 7.94 (s, 1H), 7.36 (s, 1H), 6.60 (d, J=3.29, 1H), 4.01 (s, 2H), 3.56 (d, 2H), 3.21 (s, 3H), 3.01 (m, 4H), 2.24 (m, 2H), 2.22 (s, 1H); MS m/z 324.1 (M+H)+.

Workup

  1. custompurged under nitrogen for 10 min
  2. customthe reaction mixture was degassed
  3. custompurged again for 15 min
  4. customThe resulting reaction contents
  5. customunder sealed condition
  6. customAfter completion of the reaction the mixture
  7. filtrationfiltered through Celite
  8. distillationthe organic layer was distilled off
  9. customto get the crude product

Sources & evidence

ORD record
ord-a01704a7e6c04545b02c8e2b1c211b0f
Source dataset
uspto-grants-2015_11
Patent number
US09187473B2

Reaction notes

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