Water → 2-(3-(tert-butylamino)-2-methylpyrido[3,4-b]pyrazin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1056247Notes

Reaction equation

HRID 1056247 reaction equation
CC1(C)C(C)(C)OB([C:9]2[NH:17][C:16]3[CH2:15][CH2:14][NH:13][C:12](=[O:18])[C:11]=3[CH:10]=2)O1.[C:20]([NH:24][C:25]1[N:30]=[C:29]2[C:31](Cl)=[N:32][CH:33]=[CH:34][C:28]2=[N:27][C:26]=1[CH3:36])([CH3:23])([CH3:22])[CH3:21].O.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.C(Cl)(Cl)Cl.CC(O)C.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]>[C:20]([NH:24][C:25]1[N:30]=[C:29]2[C:31]([C:9]3[NH:17][C:16]4[CH2:15][CH2:14][NH:13][C:12](=[O:18])[C:11]=4[CH:10]=3)=[N:32][CH:33]=[CH:34][C:28]2=[N:27][C:26]=1[CH3:36])([CH3:23])([CH3:22])[CH3:21]

Participants

8

Reactant 4

HCID 962WaterHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 89781928N-(tert-butyl)-5-chloro-2-methylpyrido[3,4-b]pyrazin-3-amineHCID 897834962-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-C]pyridin-4-one

Product 1

HCID 897833592-(3-(tert-butylamino)-2-methylpyrido[3,4-b]pyrazin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneYield 24%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (609) (31 mg, 0.12 mmol) and N-(tert-butyl)-5-chloro-2-methylpyrido[3,4-b]pyrazin-3-amine (15 mg, 0.06 mmol) in 1,4-Dioxane (0.8 mL)/Water (0.2 mL) followed by Xphos (2.8 mg, 6.0 μmol) (Sigma Aldich), Pd2dba3 (2.7 mg, 3.0 μmol) (Strem) and K2PO4 (38 mg, 0.18 mmol) (Sigma Aldich). The reaction mixture was stirred and heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 1 h. The mixture was diluted with CHCl3/iPrOH (4:1, 30 mL) and washed with water. The organic layer was dried (MgSO4), filtered and concentrated. The residue was purified with prep-TLC (eluted with 8% MeOH in DCM) to give 2-(3-(tert-butylamino)-2-methylpyrido[3,4-b]pyrazin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (5.0 mg, 0.014 mmol, 24% yield) as a light brown solid. MS (ESI, pos. ion) m/z: 351.1 (M+1); 1H NMR (400 MHz, MEOH-D4-d4) δ ppm 8.33 (1H, d, J=5.5 Hz), 7.79 (1H, s), 7.45 (1H, d, J=5.5 Hz), 3.62 (2H, t, J=7.0 Hz), 3.01 (2H, t, J=7.0 Hz), 2.62 (3H, s), 1.70 (9H, s).

Workup

  1. customA glass microwave reaction vessel
  2. washwashed with water
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified with prep-TLC (eluted with 8% MeOH in DCM)

Sources & evidence

ORD record
ord-494b63ded5ae48488f52e42e909d0a7a
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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