Cesium carbonate → HCID 86679608, compound

HRID 577662Notes

Reaction equation

HRID 577662 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=2)[C:5]2[C:10]([F:11])=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1.[CH3:30][N:31]1[CH:35]=[CH:34][C:33]([NH2:36])=[N:32]1.C([O-])([O-])=O.[Cs+].[Cs+].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>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]>[F:11][C:10]1[C:5]2[C:4]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=3)=[N:3][C:2]([NH:36][C:33]3[CH:34]=[CH:35][N:31]([CH3:30])[N:32]=3)=[N:7][C:6]=2[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:9]=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 86679606HCID 86679606, compound

Product 1

HCID 86679608HCID 86679608, compoundYield 95.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 2-chloro-5-fluoro-4-(3-nitrophenoxy)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (483 mg, 1.1 mmol), in 1,4-dioxane (12 mL) was added 1-methyl-1H-pyrazol-3-amine (128 mg, 1.32 mmol), Cs2CO3 (717 mg, 2.2 mmol), Xantphos (66 mg, 0.11 mmol) and Pd2(dba)3 (101 mg, 0.11 mmol). The reaction vial was flushed with nitrogen, capped, stirred and heated at 140° C. in a microwave reactor for 45 min. After removing the reaction solvent, the residue was partitioned in EtOAc (120 mL) and water (20 mL). The organic layer was separated, washed with water (20 mL) and brine (10 mL), dried over Na2SO4 and evaporated. Purification via flash chromatography with a gradient of 0%-50% EtOAc in heptanes afforded the title compound (523 mg, 95% yield) as a thick oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.62 (s, 1H) 8.28-8.32 (m, 1H) 8.26 (d, J=8.06 Hz, 1H) 7.90-7.95 (m, 1H) 7.81-7.88 (m, 1H) 7.45 (br. s., 1H) 7.32 (d, J=2.27 Hz, 1H) 5.52 (s, 2H) 3.74 (s, 3H) 3.55-3.66 (m, 2H) 0.94 (t, J=8.18 Hz, 2H) 0.00 (s, 9H). m/z (APCI+) for C22H26FN7O4Si 500.1 (M+H)+.

Workup

  1. customThe reaction
  2. customvial was flushed with nitrogen
  3. customcapped
  4. customAfter removing the reaction solvent
  5. customthe residue was partitioned in EtOAc (120 mL)
  6. customThe organic layer was separated
  7. washwashed with water (20 mL) and brine (10 mL)
  8. dry with materialdried over Na2SO4
  9. customevaporated
  10. customPurification via flash chromatography with a gradient of 0%-50% EtOAc in heptanes

Sources & evidence

ORD record
ord-ebb5e206a3084a4c93c3c59aaaa088b3
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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