Cesium carbonate → N,N-Dicyclopropyl-6-ethyl-1-methyl-4-(1-methyl-1H-pyrazol-3-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

HRID 220398Notes

Reaction equation

HRID 220398 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH2:7])=[N:3]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+].Br[C:57]1[N:62]=[C:61]2[N:63]([CH2:75][CH3:76])[C:64]([C:66]([N:68]([CH:72]3[CH2:74][CH2:73]3)[CH:69]3[CH2:71][CH2:70]3)=[O:67])=[CH:65][C:60]2=[C:59]2[N:77]([CH3:80])[CH:78]=[N:79][C:58]=12>COCCOC.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]>[CH:72]1([N:68]([CH:69]2[CH2:70][CH2:71]2)[C:66]([C:64]2[N:63]([CH2:75][CH3:76])[C:61]3=[N:62][C:57]([NH:7][C:4]4[CH:5]=[CH:6][N:2]([CH3:1])[N:3]=4)=[C:58]4[N:79]=[CH:78][N:77]([CH3:80])[C:59]4=[C:60]3[CH:65]=2)=[O:67])[CH2:74][CH2:73]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 1372541-Methyl-3-aminopyrazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 581805664-Bromo-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

Product 1

HCID 58180500N,N-Dicyclopropyl-6-ethyl-1-methyl-4-(1-methyl-1H-pyrazol-3-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamideYield 29.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a vial containing 1-methyl-1H-pyrazol-3-amine (11.89 mg, 0.122 mmol), Pd2(dba)3 (4.67 mg, 5.10 μmol), Xantphos (5.90 mg, 10.20 μmol), and cesium carbonate (100 mg, 0.306 mmol) was added 4-bromo-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (example 97A, 41.0 mg, 0.102 mmol) in DME (1020 μL). The reaction mixture was sparged with argon for 5 min, the vial was capped, and the reaction mixture was heated at 60° C. for 4 h and 80° C. for 16 h. The reaction mixture was concentrated in vacuo. The crude residue was purified by flash column chromatography using an Isco 40 g column eluting with 0-5% MeOH/CH2Cl2 followed by additional purification with preparative HPLC. N,N-Dicyclopropyl-6-ethyl-1-methyl-4-(1-methyl-1H-pyrazol-3-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (13 mg, 0.030 mmol, 29.5% yield) was isolated as a white solid.

Workup

  1. customThe reaction mixture was sparged with argon for 5 min
  2. customthe vial was capped
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customThe crude residue was purified by flash column chromatography
  5. washeluting with 0-5% MeOH/CH2Cl2
  6. customfollowed by additional purification with preparative HPLC

Sources & evidence

ORD record
ord-c51d5603b1684694ac38d2b943c22c04
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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