Cesium carbonate → HCID 90041275, compound

HRID 523013Notes

Reaction equation

HRID 523013 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:5]2=[N:6][CH:7]=1.[CH3:26][N:27]1[C:35]2[CH2:34][CH2:33][CH2:32][NH:31][C:30]=2[CH:29]=[N: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+]>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].O1CCOCC1>[C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([N:31]3[CH2:32][CH2:33][CH2:34][C:35]4[N:27]([CH3:26])[N:28]=[CH:29][C:30]3=4)[N:3]=2)[N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideHCID 83872254HCID 83872254, compound

Product 1

HCID 90041275HCID 90041275, compoundYield 99.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A microwave vial was charged with a mixture of 2-bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (68.5 mg, 160 μmol), 1-methyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridine (22 mg, 160 μmol), xantphos (27.8 mg, 48.1 μmol), Pd2(dba)3 (14.7 mg, 16.0 μmol), Cs2CO3 (105 mg, 321 μmol) and dioxane (2 mL). The reaction mixture was purged with argon and then heated to 150° C. for 20 min under microwave irradiation. The mixture was diluted with CH2Cl2 and then filtered through a pad of celite. The filtrate was concentrated in vacuo and the residue purified by chromatography (40 g column, 50 μm silica-gel from Analogix, 0 to 5% 9:1 methanol:ammonium hydroxide in CH2Cl2, min) to give N-tert-butyl-2-(1-methyl-6,7-dihydro-1H-pyrazolo[4,3-b]pyridin-4(5H)-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (77 mg, 99%) as a yellow foam. 1H NMR (CHLOROFORM-d) δ: 8.29 (s, 1H), 8.14 (s, 1H), 8.10 (s, 1H), 7.88 (s, 1H), 5.63 (s, 2H), 3.93-4.01 (m, 2H), 3.87 (s, 3H), 3.52-3.63 (m, 2H), 2.80-2.91 (m, 2H), 2.16-2.29 (m, 2H), 1.55-1.61 (m, 11H), 0.87-1.02 (m, 2H), 0.00 (s, 9H). MS (EI/CI) m/z: 484.0 [M+H]+.

Workup

  1. customThe reaction mixture was purged with argon
  2. additionThe mixture was diluted with CH2Cl2
  3. filtrationfiltered through a pad of celite
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue purified by chromatography (40 g column, 50 μm silica-gel from Analogix, 0 to 5% 9:1 methanol:ammonium hydroxide in CH2Cl2, min)

Sources & evidence

ORD record
ord-ce07aee47080489b876605b317a2e99e
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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