Triethylamine → HCID 11643282, compound

HRID 1663609Notes

Reaction equation

HRID 1663609 reaction equation
[C:1]([N:8]([CH2:21][CH2:22][C:23]#[CH:24])[S:9]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=1)(=[O:11])=[O:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH:25]([NH:38][C:39]1[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][C:40]=1I)([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(N(CC)CC)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CN(C=O)C>[C:4]([O:3][C:1]([N:8]([CH2:21][CH2:22][C:23]#[C:24][C:40]1[CH:41]=[C:42]([Cl:45])[CH:43]=[CH:44][C:39]=1[NH:38][CH:25]([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[S:9]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=1)(=[O:11])=[O:10])=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 11486936HCID 11486936, compoundHCID 86603350HCID 86603350, compound

Product 1

HCID 11643282HCID 11643282, compoundYield 94%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst2×HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
55 °C

Procedure

A warm (45° C.) solution of N-BOC-N-but-3-ynyl-(3,4-dichloro-phenyl)-methanesulfonamide (347 g, 0.885 mol), dichlorobis(triphenylphosphine)palladium (II) (3.50 g, 4.99 mmol), and DMF (700 mL) was added slowly over 8 h to a warm (55° C.), stirred mixture of benzhydryl-(4-chloro-2-iodo-phenyl)-amine (350 g, 0.833 mol), dichlorobis(triphenylphosphine)palladium (II) (3.5 g, 4.99 mmol), copper (I) iodide (20.0 g, 0.105 mol), triethylamine, (259 g, 2.56 mol), and DMF (250 mL). The reaction mixture was stirred and maintained at 55° C. for 30 m after complete addition. The reaction mixture was distilled at reduced pressure using a heating bath temperature of 40-45° C. to remove triethylamine. The reaction mixture was filtered through a celite pad. The pad was washed with DMF (40 mL). 2-Propanol (280 mL) was added to the filtrate. The mixture was warmed to 55° C. Water (280 mL) was added slowly over 1 h to the stirred mixture. The stirred mixture was maintained at 55° C. for 30 m after complete water addition. The mixture was cooled to 10° C. The solid product was collected by filtration and washed with cold 1/1 (v/v) IPA/water (2×300 mL). The solid was vacuum dried at <50° C. to give N-t-butoxycarbonyl-N{4-[2-(benzhydryl-amino)-5-chloro-phenyl]-but-3-ynyl}-C-(3,4-dichlorophenyl)-methanesulfonamide (534.5 g, 94%) with 98% purity (as determined by HPLC).

Workup

  1. additionwas added slowly over 8 h to
  2. stirringThe reaction mixture was stirred
  3. temperaturemaintained at 55° C. for 30 m
  4. additionafter complete addition
  5. distillationThe reaction mixture was distilled at reduced pressure
  6. customtemperature of 40-45° C.
  7. customto remove triethylamine
  8. filtrationThe reaction mixture was filtered through a celite pad
  9. washThe pad was washed with DMF (40 mL)
  10. addition2-Propanol (280 mL) was added to the filtrate
  11. temperatureThe mixture was warmed to 55° C
  12. additionWater (280 mL) was added slowly over 1 h to the stirred mixture
  13. temperatureThe stirred mixture was maintained at 55° C. for 30 m
  14. additionafter complete water addition
  15. temperatureThe mixture was cooled to 10° C
  16. filtrationThe solid product was collected by filtration
  17. washwashed with cold 1/1 (v/v) IPA/water (2×300 mL)
  18. customdried at <50° C.

Sources & evidence

ORD record
ord-2e38ba31b18647eba747ae9ce4f62788
Source dataset
uspto-grants-2011_10
Patent number
US08034960B2

Reaction notes

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