1,2-Dichloroethane → N-(6-acetyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-3-(4-fluoro-phenyl)-3-(3-trifluoromethyl-benzenesulfonylamino)-propionamide

HRID 32116Notes

Reaction equation

HRID 32116 reaction equation
C(O[C:6](=[O:21])[NH:7][CH:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18](=[O:20])[CH3:19])=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.Cl.NC1CCCC2C=C(C(=O)C)C=CC1=2.[F:37][C:38]1[CH:43]=[CH:42][C:41]([CH:44]([NH:49][S:50]([C:53]2[CH:58]=[CH:57][CH:56]=[C:55]([C:59]([F:62])([F:61])[F:60])[CH:54]=2)(=[O:52])=[O:51])[CH2:45]C(O)=O)=[CH:40][CH:39]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>Cl.CCOC(C)=O.C(Cl)Cl.CN(C=O)C>[C:18]([C:14]1[CH:13]=[C:12]2[C:17](=[CH:16][CH:15]=1)[CH:8]([NH:7][C:6](=[O:21])[CH2:45][CH:44]([C:41]1[CH:40]=[CH:39][C:38]([F:37])=[CH:43][CH:42]=1)[NH:49][S:50]([C:53]1[CH:58]=[CH:57][CH:56]=[C:55]([C:59]([F:60])([F:62])[F:61])[CH:54]=1)(=[O:51])=[O:52])[CH2:9][CH2:10][CH2:11]2)(=[O:20])[CH3:19]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 454662383-(4-Fluorophenyl)-3-(3-trifluoromethyl-benzenesulfonylamino)-propionic acidHCID 686795031-(5-Amino-5,6,7,8-tetrahydro-naphthalen-2-yl)-ethanone hydrogen chlorideHCID 68680146Tert-butyl 6-acetyl-1,2,3,4-tetrahydronaphthalen-1-ylcarbamate

Product 1

HCID 68929305N-(6-acetyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-3-(4-fluoro-phenyl)-3-(3-trifluoromethyl-benzenesulfonylamino)-propionamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 21866389Hydrogen chloride-ethyl acetateSolvent

Procedure

A mixture of (6-acetyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-carbamic acid tert-butyl ester (Step e, 543 mg, 1.88 mmol, 1.0 eq) in HCl/EtOAc (4.7 M, 20 mL) was stirred at RT for 200 min. The solvent was removed with a rotary evaporator, and the resulting 1-(5-amino-5,6,7,8-tetrahydro-naphthalen-2-yl)-ethanone hydrogen chloride was dried in vacuo. A mixture of 1-(5-amino-5,6,7,8-tetrahydro-naphthalen-2-yl)-ethanone hydrogen chloride, 3-(4-fluoro-phenyl)-3-(3-trifluoromethyl-benzenesulfonylamino)-propionic acid (882 mg, 2.26 mmol, 1.2 eq), EDC (Aldrich, 649 mg, 3.38 mmol, 1.8 eq), HOBt (Aldrich, 51 mg, 0.376 mmol, 0.2 eq) and DIEA (Aldrich, 486 mg, 3.76 mmol, 2.0 eq) in CH2Cl2 (20 mL) and DMF (5 mL) was stirred at RT overnight. The reaction was quenched with H2O (100 mL). The crude was extracted with CH2Cl2 (150 mL×3). The extract phase was washed with saturated NaCl, dried over Na2SO4, filtered and concentrated. Flash column chromatography (silica gel, 0-5% MeOH—CH2Cl2) afforded the title compound as an off-white solid. MS (ESI, pos. ion) m/z: 563 (M+1).

Workup

  1. customThe solvent was removed with a rotary evaporator
  2. dry with materialthe resulting 1-(5-amino-5,6,7,8-tetrahydro-naphthalen-2-yl)-ethanone hydrogen chloride was dried in vacuo
  3. stirringwas stirred at RT overnight
  4. customThe reaction was quenched with H2O (100 mL)
  5. extractionThe crude was extracted with CH2Cl2 (150 mL×3)
  6. washThe extract phase was washed with saturated NaCl
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-a16e7227010c461e85dbaf56530e6547
Source dataset
uspto-grants-2008_09
Patent number
US07425631B2

Reaction notes

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