Cesium carbonate → HCID 90040990, compound

HRID 523010Notes

Reaction equation

HRID 523010 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[CH:35]=[C:30]2[NH:31][CH2:32][CH2:33][CH2:34][C:29]2=[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+]>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]>[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:29]4=[N:28][N:27]([CH3:26])[CH:35]=[C:30]34)[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 86767714HCID 86767714, compound

Product 1

HCID 90040990HCID 90040990, compoundYield 99%

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 (77.9 mg, 182 μmol), 2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-b]pyridine (25 mg, 182 μmol), xantphos (31.6 mg, 54.7 μmol), Pd2(dba)3 (16.7 mg, 18.2 μmol) and Cs2CO3 (119 mg, 364 μmol) in dioxane (2 mL). The 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 m silica-gel from Analogix, 0 to 5% 9:1 methanol:ammonium hydroxide in CH2Cl2, 20 min) to give N-tert-butyl-2-(2-methyl-6,7-dihydro-2H-pyrazolo[4,3-b]pyridin-4(5H)-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (87 mg, 99%) as a yellow foam. 1H NMR (CHLOROFORM-d) δ: 8.20 (s, 1H), 8.15 (s, 1H), 7.99 (s, 1H), 7.85 (s, 1H), 5.64 (s, 2H), 3.91 (s, 3H), 3.50-3.63 (m, 2H), 2.93 (t, J=6.6 Hz, 2H), 2.15-2.30 (m, 2H), 1.53-1.62 (m, 11H), 0.86-1.05 (m, 2H), 0.00 (s, 9H). MS (EI/CI) m/z: 484.0 [M+H].

Workup

  1. customThe 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 m silica-gel from Analogix, 0 to 5% 9:1 methanol:ammonium hydroxide in CH2Cl2, 20 min)

Sources & evidence

ORD record
ord-df01d5aa27964aab962eafa51e9eb1bd
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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