Sodium Carbonate → Tert-butyl 4-[4-amino-7-(4-pyridinyl)thieno[3,2-c]pyridin-3-yl]phenylcarbamate

HRID 2390627Notes

Reaction equation

HRID 2390627 reaction equation
[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:13][CH:12]=3)=[CH:9][S:10][C:6]=2[C:5](I)=[CH:4][N:3]=1.[N:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.CO.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]>[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:13][CH:12]=3)=[CH:9][S:10][C:6]=2[C:5]([C:29]2[CH:30]=[CH:31][N:26]=[CH:27][CH:28]=2)=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 18451463Tert-butyl 4-(4-amino-7-iodothieno[3,2-c]pyridin-3-yl)phenylcarbamate

Product 1

HCID 18451458Tert-butyl 4-[4-amino-7-(4-pyridinyl)thieno[3,2-c]pyridin-3-yl]phenylcarbamateYield 46.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of Example 77A (1.559 g, 3.34 mmol), 4-pyridylboronic acid (0.431 g, 3.51 mmol) and Na2CO3 (0.37 g, 3.51 mmol) in THF/methanol/water (12 mL:2.4 mL:4 mL) was degassed by bubbling nitrogen through the solution for 15 minutes, then treated with Pd(dppf)Cl2 (136 mg, 0.17 mmol). The reaction vessel was sealed and heated to 90° C. for 17 hours. The reaction was cooled to room temperature and partitioned between water and ethyl acetate. The aqueous phase was extracted twice with ethyl acetate. The combined extracts were dried (Na2SO4), filtered, concentrated, and the residue was purified by flash column chromatography on silica gel with 3% methanol/dichloromethane to provide 0.65 g (46%) of the desired product. MS (ESI(+)) m/e 419 (M+H)+.

Workup

  1. customby bubbling nitrogen through the solution for 15 minutes
  2. customThe reaction vessel was sealed
  3. temperatureThe reaction was cooled to room temperature
  4. custompartitioned between water and ethyl acetate
  5. extractionThe aqueous phase was extracted twice with ethyl acetate
  6. dry with materialThe combined extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customthe residue was purified by flash column chromatography on silica gel with 3% methanol/dichloromethane

Sources & evidence

ORD record
ord-c35fa0c88c5944af8f16f5c80b60fdba
Source dataset
uspto-grants-2012_09
Patent number
US08273736B2

Reaction notes

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