Triethylamine → Ethyl 2-(3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)phenylamino)-2-oxoacetate

HRID 1676235Notes

Reaction equation

HRID 1676235 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[CH:17][S:18][C:11]=12)[NH2:5].C(N(CC)CC)C.Cl[C:27](=[O:33])[C:28]([O:30][CH2:31][CH3:32])=[O:29]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:27](=[O:33])[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[CH:17][S:18][C:11]=12

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 20884Ethoxalyl chlorideHCID 594244303-Fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)aniline

Product 1

HCID 24983242Ethyl 2-(3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)phenylamino)-2-oxoacetateYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)aniline (prepared in Example 1, Step B; 0.78 g, 3.0 mmol), triethylamine (0.84 mL, 6.0 mmol), and CH2Cl2 (5 mL) was added a solution of ethyl 2-chloro-2-oxoacetate (0.45 g, 3.3 mmol) in CH2Cl2 (1 mL) dropwise at room temperature. Stirring was continued for 15 minutes. The mixture was washed with water (3×5 mL), dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by Biotage Flash 40 silica gel chromatography, eluting with 30% EtOAc/hexanes, then 1:1 EtOAc/hexanes. The product was obtained as a white powder (656 mg, 61%). 1H NMR (400 MHz, CDCl3) δ 9.10 (s, 1H), 8.53 (d, J=6 Hz, 1H), 7.85 (d, J=12 Hz, 1H), 7.76 (d, J=6 Hz, 1H), 7.58 (d, J=6 Hz, 1H), 7.39 (d, J=9 Hz, 1H), 7.30 (d, J=9 Hz, 1H), 6.52 (d, J=6 Hz, 1H), 4.44 (q, J=7 Hz, 2H), 1.44 (t, J=7 Hz, 3H). LRMS (APCI pos) m/e 361 (M+1). HPLC: 99% purity (220 nm).

Workup

  1. washThe mixture was washed with water (3×5 mL)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting crude was purified by Biotage Flash 40 silica gel chromatography
  6. washeluting with 30% EtOAc/hexanes

Sources & evidence

ORD record
ord-528ed1081d624ca1bbf4b1493fce7d75
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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