Sodium Carbonate → HCID 178453659, compound

HRID 577711Notes

Reaction equation

HRID 577711 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([O:20][C@H:21]2[CH2:24][C@H:23]([CH2:25][NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:22]2)[C:5]2[C:10](I)=[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.[N:34]1[CH:39]=[CH:38][CH:37]=[C:36](B(O)O)[CH:35]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:29]([O:28][C:27](=[O:33])[NH:26][CH2:25][C@H:23]1[CH2:24][C@H:21]([O:20][C:4]2[C:5]3[C:10]([C:36]4[CH:35]=[N:34][CH:39]=[CH:38][CH:37]=4)=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=3[N:7]=[C:2]([Cl:1])[N:3]=2)[CH2:22]1)([CH3:32])([CH3:31])[CH3:30]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 27343783-Pyridinylboronic acidHCID 178453660HCID 178453660, compound

Product 1

HCID 178453659HCID 178453659, compoundYield 77.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of tert-butyl {trans-3-[(2-chloro-5-iodo-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4yl)oxy]cyclobutyl}methylcarbamate (450 mg, 0.7 mmol), pyridin-3-ylboronic acid (95 mg, 0.8 mmol), 1,4-dioxane (10 mL), water (3 mL), sodium carbonate (94 mg, 0.9 mmol), PdCl2(dppf) (54 mg, 0.07 mmol) was stirred and heated at 70° C. for 1 hr. The reaction was diluted with ethyl acetate (60 mL) and water (15 mL). The organic layer was separated, washed with brine (20 mL), dried over Na2SO4 and evaporated to give a residue, which was purified via flash chromatography (eluting with a gradient of 0%-100% EtOAc in heptanes) to give the title compound (304 mg, 73% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.90 (d, J=1.83 Hz, 1H) 8.53 (dd, J=4.71, 1.41 Hz, 1H) 8.12 (dt, J=8.01, 1.86 Hz, 1H) 7.98 (s, 1H) 7.48 (dd, J=7.82, 4.89 Hz, 1H) 5.58 (s, 2H) 5.40 (t, J=6.60 Hz, 1H) 4.67 (br. s., 1H) 3.52-3.65 (m, 2H) 2.78 (s, 3H) 2.59-2.71 (m, 2H) 2.21-2.37 (m, 2H) 1.38 (s, 9H) 0.82-0.93 (m, 2H) −0.06 (s, 9H). m/z (APCI+) for C27H38ClN5O4Si 560.2 (M+H)+.

Workup

  1. customThe organic layer was separated
  2. washwashed with brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customto give a residue, which
  6. customwas purified via flash chromatography (
  7. washeluting with a gradient of 0%-100% EtOAc in heptanes)

Sources & evidence

ORD record
ord-97ab5d78baca4cc781b707982b75a989
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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