Cesium carbonate → HCID 22477513, compound

HRID 549035Notes

Reaction equation

HRID 549035 reaction equation
[C:1](=[O:4])([O-])[O-].[Cs+].[Cs+].Cl[C:8]1[CH:13]=[CH:12][N:11]=[C:10]2[N:14]([S:29]([C:32]3[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=3)(=[O:31])=[O:30])[C:15]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH3:27])[CH:24]=4)[N:19]([CH3:28])[CH:18]=3)=[CH:16][C:9]=12.C1(P(C2CCCCC2)C2C=CC=CC=2[C:52]2C=CC=C[C:53]=2[N:58](C)[CH3:59])CCCCC1>COCCOC.N1CCOCC1>[N:58]1([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[N:14]([S:29]([C:32]4[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=4)(=[O:31])=[O:30])[C:15]([C:17]4[C:25]5[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH3:27])[CH:24]=5)[N:19]([CH3:28])[CH:18]=4)=[CH:16][C:9]=23)[CH2:59][CH2:1][O:4][CH2:52][CH2:53]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 22477518HCID 22477518, compound

Product 1

HCID 22477513HCID 22477513, compound

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolvent3×HCID 8083MorpholineSolvent

Conditions

Temperature
80 °C

Procedure

Into a tube containing cesium carbonate (153 mg) was added (i) a solution of 4-chloro-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine [50 mg, Reference Example 13(i)] in 1,2-dimethoxyethane (1 mL), (ii) tris-(dibenzylideneacetone)-dipalladium(0) (15 mg) in 1,2-dimethoxyethane (0.5 mL), (iii) 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)-biphenyl (42 mg) in 1,2-dimethoxyethane (0.5 mL) and (iv) morpholine (30 mg). This mixture was heated under agitation at 80° C. for 15 hours and then filtered on a silica plug that was then washed with dichloromethane and methanol (1 mL each). The combined filtrate plus washings were evaporated using a centrifuge evaporator. The residue was dissolved in dimethylsulfoxyde (1 mL) and then subjected to LC-MS triggered purification (injections corresponding to 20 mg crude compound) affording 4-(morpholine-4yl)-2-(5-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine which was resuspended in methanol (2 mL) and magnesium turnings (89 mg, 15 equivalents from the mass measured after evaporation of the chromatographic solvent) were added. The suspension was then agitated for 15 hours at room temperature and then filtered on Celite. The filtrate was evaporated and the residue was solubilized in dimethylsulfoxide and subjected to LC-MS triggered purification according affording the title compound. LC-MS: METHOD C: RT=3.27 minutes, 363.3[M+H]+.

Workup

  1. filtrationfiltered on a silica plug that
  2. washwas then washed with dichloromethane and methanol (1 mL each)
  3. customThe combined filtrate plus washings were evaporated
  4. customa centrifuge evaporator
  5. dissolutionThe residue was dissolved in dimethylsulfoxyde (1 mL)
  6. custompurification (injections corresponding to 20 mg crude compound)

Sources & evidence

ORD record
ord-7515f98e21914370aed0c01a9db5af64
Source dataset
uspto-grants-2011_05
Patent number
US07943616B2

Reaction notes

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