Sodium Carbonate → Methyl 6-amino-5-{5-[(tert-butoxycarbonyl)amino]-1-benzothien-2-yl}nicotinate

HRID 2205554Notes

Reaction equation

HRID 2205554 reaction equation
[NH2:1][C:2]1[C:11](I)=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[C:13]([O:17][C:18](=[O:38])[NH:19][C:20]1[CH:37]=[CH:36][C:23]2[S:24][C:25](B3OC(C)(C)C(C)(C)O3)=[CH:26][C:22]=2[CH:21]=1)([CH3:16])([CH3:15])[CH3:14].C(=O)([O-])[O-].[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C:2]1[C:11]([C:25]2[S:24][C:23]3[CH:36]=[CH:37][C:20]([NH:19][C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:38])=[CH:21][C:22]=3[CH:26]=2)=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 15350913Methyl 6-amino-5-iodopyridine-3-carboxylateHCID 131735691Tert-butyl (2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[b]thiophen-5-yl)carbamate

Product 1

HCID 121267855Methyl 6-amino-5-{5-[(tert-butoxycarbonyl)amino]-1-benzothien-2-yl}nicotinate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To the degassed mixture of methyl 6-amino-5-iodonicotinate (4.17 g, 15 mmol, 1 eq), {[2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophen-5-yl]-carbamic acid tert-butyl ester} (6.47 g, 1.15 eq), and aq sodium carbonate (2M, 22.5 mL, 3 eq) in dioxane (30 mL) was added Ph3P (393 mg, 0.1 eq) and Pd(OAc)2 (340 mg, 0.1 eq). The mixture was heated to 50° C. with vigorous stirring for 45 minutes. The reaction mixture was then partitioned between aq NH4Cl and EtOAc. The organic layer was isolated, washed with sat aq NaHCO3, brine, and finally dried with anhydrous sodium sulfate. The upper solution-layer was decanted, concentrated, and the solid residue was treated with EtOAc-Hex (1:4) with stirring at room temperature for 3 hours. methyl 6-amino-5-{5-[(tert-butoxycarbonyl)amino]-1-benzothien-2-yl}nicotinate was obtained upon filtration as a slightly green-yellowish solid.

Workup

  1. customThe reaction mixture was then partitioned between aq NH4Cl and EtOAc
  2. customThe organic layer was isolated
  3. washwashed with sat aq NaHCO3, brine
  4. dry with materialfinally dried with anhydrous sodium sulfate
  5. customThe upper solution-layer was decanted
  6. concentrationconcentrated
  7. additionthe solid residue was treated with EtOAc-Hex (1:4)
  8. stirringwith stirring at room temperature for 3 hours

Sources & evidence

ORD record
ord-b56e6c5e699945d19e7533252d0cee10
Source dataset
uspto-grants-2016_06
Patent number
US09371314B2

Reaction notes

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