Sodium Carbonate → Tert-butyl 4-(4-aminofuro[3,2-c]pyridin-3-yl)-2-methoxyphenylcarbamate

HRID 2390686Notes

Reaction equation

HRID 2390686 reaction equation
Br[C:2]1[C:6]2[C:7]([NH2:11])=[N:8][CH:9]=[CH:10][C:5]=2[O:4][CH:3]=1.[CH3:12][O:13][C:14]1[CH:19]=[C:18](B2OC(C)(C)C(C)(C)O2)[CH:17]=[CH:16][C:15]=1[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[NH2:11][C:7]1[C:6]2[C:2]([C:18]3[CH:17]=[CH:16][C:15]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:34])[CH3:35])=[C:14]([O:13][CH3:12])[CH:19]=3)=[CH:3][O:4][C:5]=2[CH:10]=[CH:9][N:8]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 177502214-(tert-Butoxycarbonylamino)-3-methoxyphenylboronic acid, pinacol esterHCID 184507953-Bromofuro[3,2-c]pyridin-4-amine

Product 1

HCID 18451465Tert-butyl 4-(4-aminofuro[3,2-c]pyridin-3-yl)-2-methoxyphenylcarbamateYield 98.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 3-bromofuro[3,2-c]pyridin-4-amine (0.443 g, 2.1 mmol) in 1,2-dimethoxyethane (16 mL) and water (8 mL) was treated with tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (0.872 g, 2.5 mmol), sodium carbonate (0.749 g, 7.1 mmol) and tetrakis triphenylphosphine palladium (0) (0.144 g, 0.12 mmol) at 80° C. for 18 hours. The organic solvent was removed in vacuo and the aqueous mixture was extracted with ethyl acetate (3×10 mL). The combined organic phases were dried over anhydrous magnesium sulfate and the solvent was removed in vacuo. The residue was purified by flash column chromatography on silica gel using heptane/ethyl acetate (4:1) followed by ethyl acetate as an eluents to give the title compound (0.734 g, 85%) as a tan solid. 1H NMR (DMSO-d6, 400 MHz) δ 8.07 (s, 1H), 7.96 (s, 1H), 7.87 (d, 1H), 7.84 (d, 1H), 7.14 (d, 1H), 7.05 (dd, 1H), 6.94 (d, 1H), 5.55-5.62 (bs, 2H), 3.87 (s, 3H), 1.48 (s, 9H); RP-HPLC (Conditions f) Rt 12.13 min.; MS: MH+ 356.

Workup

  1. customThe organic solvent was removed in vacuo
  2. extractionthe aqueous mixture was extracted with ethyl acetate (3×10 mL)
  3. dry with materialThe combined organic phases were dried over anhydrous magnesium sulfate
  4. customthe solvent was removed in vacuo
  5. customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-da80bf08501f49e1a2252085dce0f381
Source dataset
uspto-grants-2012_09
Patent number
US08273736B2

Reaction notes

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