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

HRID 17131Notes

Reaction equation

HRID 17131 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 (136mg, 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-f47544f5ee31496b85f33eb5ce7b544f
Source dataset
uspto-grants-2010_06
Patent number
US07737160B2

Reaction notes

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