Triethylamine → 5-fluoro-3-iodo-1H-indole-2-carboxylic acid (3-oxo-propyl)-amide

HRID 29785Notes

Reaction equation

HRID 29785 reaction equation
C(Cl)(=O)C(Cl)=O.[OH:7][CH2:8][CH2:9][CH2:10][NH:11][C:12]([C:14]1[NH:15][C:16]2[C:21]([C:22]=1[I:23])=[CH:20][C:19]([F:24])=[CH:18][CH:17]=2)=[O:13].CCN(CC)CC>C(Cl)Cl.CS(C)=O>[O:7]=[CH:8][CH2:9][CH2:10][NH:11][C:12]([C:14]1[NH:15][C:16]2[C:21]([C:22]=1[I:23])=[CH:20][C:19]([F:24])=[CH:18][CH:17]=2)=[O:13]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 597892045-Fluoro-3-iodo-1H-indole-2-carboxylic acid (3-hydroxy-propyl)-amide

Product 1

HCID 597892255-fluoro-3-iodo-1H-indole-2-carboxylic acid (3-oxo-propyl)-amide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of oxalyl chloride (3.68 g, 30 mmol) in anhydrous CH2Cl2 (50 mL) at −40° C. is added DMSO (4.52 g, 57.9 mmol) drop-wise. The mixture is stirred at this temperature for 5 minutes. 5-Fluoro-3-iodo-1H-indole-2-carboxylic acid (3-hydroxy-propyl)-amide, prepared as in reference 12, (6.99 g, 19.3 mmol) is dissolved in CH2Cl2 (800 mL) with small amount of DMSO (10 mL) and added to the above-mentioned solution at −40° C. The reaction is stirred for additional 30 minutes before adding Et3N (11.7 g, 0.116 mol). The mixture is allowed to warm to room temperature and quenched with H2O (1 L). The organic layer is separated and washed with citric acid (10%, 500 mL), saturated NaHCO3 (500 mL) and brine (500 mL). It is dried with Na2SO4 to give 5-fluoro-3-iodo-1H-indole-2-carboxylic acid (3-oxo-propyl)-amide; 1H NMR (DMSO-d6) δ 2.75 (dt, 2H, J1=1.2 Hz, J2=6.0 Hz), 3.61 (q, 2H, J=5.2 Hz), 7.06-7.17 (m, 2H), 7.45 (dd, 1H, J1=4.8 Hz, J2=8.8 Hz), 8.11 (t, 1H, J=5.6 Hz), 9.74 (t, 1H, 1.2 Hz), 12.10 (s, 1H); m/z [M++1] 361.0.

Workup

  1. additionadded to the above-mentioned solution at −40° C
  2. stirringThe reaction is stirred for additional 30 minutes
  3. customquenched with H2O (1 L)
  4. customThe organic layer is separated
  5. washwashed with citric acid (10%, 500 mL), saturated NaHCO3 (500 mL) and brine (500 mL)
  6. dry with materialIt is dried with Na2SO4

Sources & evidence

ORD record
ord-e679a5a3e40f4c9eba0c23dab1bd192f
Source dataset
uspto-grants-2008_09
Patent number
US07423031B2

Reaction notes

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