Cesium carbonate → Bms-911543

HRID 1188068Notes

Reaction equation

HRID 1188068 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([NH2:8])=[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+].[CH:57]1([N:60]([CH:79]2[CH2:81][CH2:80]2)[C:61]([C:63]2[N:76]([CH2:77][CH3:78])[C:66]3=[N:67][C:68](I)=[C:69]4[N:73]=[CH:72][N:71]([CH3:74])[C:70]4=[C:65]3[CH:64]=2)=[O:62])[CH2:59][CH2:58]1>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:79]1([N:60]([CH:57]2[CH2:58][CH2:59]2)[C:61]([C:63]2[N:76]([CH2:77][CH3:78])[C:66]3=[N:67][C:68]([NH:8][C:4]4[CH:5]=[C:6]([CH3:7])[N:2]([CH3:1])[N:3]=4)=[C:69]4[N:73]=[CH:72][N:71]([CH3:74])[C:70]4=[C:65]3[CH:64]=2)=[O:62])[CH2:81][CH2:80]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 70177471,5-dimethyl-1H-pyrazol-3-amineHCID 581806494-iodo-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

Product 1

HCID 50922691Bms-911543Yield 31.7%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

To a vial containing 1,5-dimethyl-1H-pyrazol-3-amine (13.60 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 N,N-dicyclopropyl-6-ethyl-4-iodo-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (45.8 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 90° C. 1 h. The reaction mixture was diluted with dichloromethane and vacuum filtered through Celite. The filtrate was concentrated in vacuo. The crude residue was purified via flash column chromatography using an ISCO 12 g column eluting with 1-10% MeOH/CH2Cl2). N,N-Dicyclopropyl-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide (14 mg, 31.7% yield) was isolated as an off-white solid.

Workup

  1. customThe reaction mixture was sparged with argon for 5 min
  2. customthe vial was capped
  3. custom1 h
  4. additionThe reaction mixture was diluted with dichloromethane and vacuum
  5. filtrationfiltered through Celite
  6. concentrationThe filtrate was concentrated in vacuo
  7. customThe crude residue was purified via flash column chromatography
  8. washeluting with 1-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-1e8915b28dfb4e98b9e8f2c00e6ff6f7
Source dataset
uspto-grants-2014_03
Patent number
US08673933B2

Reaction notes

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