Cesium carbonate → Bms-911543

HRID 220390Notes

Reaction equation

HRID 220390 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-dfea846404ed4fea81b7bc61544c16f1
Source dataset
uspto-grants-2012_06
Patent number
US08202881B2

Reaction notes

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