Cesium carbonate → HCID 86679636, compound

HRID 577693Notes

Reaction equation

HRID 577693 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([N+:32]([O-:34])=[O:33])[CH:27]=2)[C:5]2[C:10]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]=2[N:7]=1.[CH3:35][N:36]1[CH:40]=[C:39]([NH2:41])[CH:38]=[N:37]1.C([O-])([O-])=O.[Cs+].[Cs+]>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].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>[CH3:35][N:36]1[CH:40]=[C:39]([NH:41][C:2]2[N:3]=[C:4]([O:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([N+:32]([O-:34])=[O:33])[CH:27]=3)[C:5]3[C:10]([C:11]4[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=4)=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:22])[CH3:23])[C:6]=3[N:7]=2)[CH:38]=[N:37]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 47709901-methyl-1H-pyrazol-4-amineHCID 86679634HCID 86679634, compound

Product 1

HCID 86679636HCID 86679636, compoundYield 199.7%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

To a microwave reaction vial was added 2-chloro-4-(3-nitrophenoxy)-5-(pyridin-3-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (130 mg, 0.26 mmol), 1-methyl-1H-pyrazol-4-amine (28 mg, 0.29 mmol, 1.1 mol eq), 1,4-dioxane (5 mL), Cs2CO3 (ca. 170 mg), Xantphos (16 mg) and Pd2(dba)3 (24 mg). The reaction vial was flushed with nitrogen, capped, stirred and heated to 140° C. using microwave at high absorption level for 45 min. The reaction was diluted with EtOAc (120 mL) and water (20 mL). The organic layer was separated, washed with water (20 mL) and with brine (10 mL), dried over Na2SO4 and evaporated to give crude product (TLC: Rf 0.2 in 100 ethyl acetate). The crude product was purified on silica to give the title compound as a green gum (290 mg, 100% yield). 1H NMR (400 MHz, methanol-d4) δ ppm 8.99 (s, 1H) 8.48 (d, J=3.78 Hz, 1H) 8.18-8.32 (m, 3H) 7.71-7.81 (m, 2H) 7.48-7.55 (m, 2H) 5.70 (s, 2H) 3.77-3.87 (m, 2H) 3.70-3.77 (m, 3H) 0.94-1.06 (m, 2H) 0.00 (s, 9H). m/z (APCI+) for C27H30N8O4Si 559.1 (M+H)+.

Workup

  1. customTo a microwave reaction
  2. customThe reaction
  3. customvial was flushed with nitrogen
  4. customcapped
  5. customfor 45 min
  6. additionThe reaction was diluted with EtOAc (120 mL) and water (20 mL)
  7. customThe organic layer was separated
  8. washwashed with water (20 mL) and with brine (10 mL)
  9. dry with materialdried over Na2SO4
  10. customevaporated
  11. customto give crude product (TLC: Rf 0.2 in 100 ethyl acetate)
  12. customThe crude product was purified on silica

Sources & evidence

ORD record
ord-2b7315a0a3ff480882607c51d0423d61
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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