Sodium Carbonate → 4-Pyridin-3-yl-2-pyridin-2-yl-7H-pyrrolo[2,3-d]pyrimidine

HRID 1878590Notes

Reaction equation

HRID 1878590 reaction equation
Cl[C:2]1[C:3]2[CH:16]=[CH:15][NH:14][C:4]=2[N:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[N:7]=1.[N:17]1[CH:22]=[CH:21][CH:20]=[C:19](B(O)O)[CH:18]=1.C([O-])([O-])=O.[Na+].[Na+].COCCOC.CCO>CC#N.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:2]2[C:3]3[CH:16]=[CH:15][NH:14][C:4]=3[N:5]=[C:6]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=3)[N:7]=2)[CH:18]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 20074477Dimethoxyethane ethanolHCID 866324274-Chloro-2-pyridin-2-yl-7H-pyrrolo[2,3-d]pyrimidine2×

Product 1

HCID 687388684-Pyridin-3-yl-2-pyridin-2-yl-7H-pyrrolo[2,3-d]pyrimidine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 178418476HCID 178418476, compoundCatalyst2×HCID 6342AcetonitrileSolvent2×

Procedure

4-Chloro-2-pyridin-2-yl-7H-pyrrolo[2,3-d]pyrimidine (Intermediate 1) (1 eq, 1.17 mmol, 285 mg) and pyridine-3-boronic acid (ABCR GmbH & Co. KG, Karlsruhe, Germany) (2 eq, 2.35 mmol, 294 mg) are dissolved in MeCN (8 ml). Then an aqueous Na2CO3 solution (2 M, 4 eq, 4.7 mmol, 2.3 ml) and PdCl2(PPh3)2 (0.1 eq, 0.117 mmol, 84 mg) are added and the resulting mixture is heated using microwave radiation at 150° C. for 20 min. Alternatively Pd(PPh3)4 and DME/EtOH (1:1) can be used instead of PdCl2(PPh3)2 and MeCN. The solvents are removed in vacuo, then aqueous NaOH solution (1 M) is added, and the solution is extracted with DCM. The organic layer is dried with MgSO4, filtered, and concentrated. The crude product is recrystallized from EtOAc affording the title compound; [M+H]+=274; 1H-NMR (400 MHz, DMSO): δ 12.52 (s, 1H), 9.46 (dd, 1H), 8.76 (m, 2H), 8.66 (td, 1H), 8.57 (td, 1H), 7.97 (dt, 1H), 7.80 (d, 1H), 7.65 (ddd, 1H), 7.48 (ddd, 1H), 7.01 (d, 1H).

Workup

  1. temperaturethe resulting mixture is heated
  2. customat 150° C.
  3. customfor 20 min
  4. customThe solvents are removed in vacuo
  5. additionaqueous NaOH solution (1 M) is added
  6. extractionthe solution is extracted with DCM
  7. dry with materialThe organic layer is dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product is recrystallized from EtOAc affording the title compound

Sources & evidence

ORD record
ord-6b75bded78fe43e687580a5d7c2e73b1
Source dataset
uspto-grants-2012_11
Patent number
US08314112B2

Reaction notes

Loading…