Diisopropylethylamine → N-{(1S)-1-[5-chloro-2-(1-{[(1R,2R,4R)-2-(2,4-difluorophenyl)-4-(dimethylamino)cyclopentyl]carbonyl}piperidin-4-yl)phenyl]ethyl}acetamide

HRID 1743955Notes

Reaction equation

HRID 1743955 reaction equation
C(N(CC)C(C)C)(C)C.Cl.[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[C@@H:19]1[CH2:23][C@@H:22]([N:24]([CH3:26])[CH3:25])[CH2:21][C@H:20]1[C:27]([OH:29])=O.Cl.[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([CH:44]2[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]2)=[C:36]([C@@H:38]([NH:40][C:41](=[O:43])[CH3:42])[CH3:39])[CH:37]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C)C=O.O>[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([CH:44]2[CH2:45][CH2:46][N:47]([C:27]([C@@H:20]3[CH2:21][C@H:22]([N:24]([CH3:25])[CH3:26])[CH2:23][C@H:19]3[C:13]3[CH:14]=[CH:15][C:16]([F:18])=[CH:17][C:12]=3[F:11])=[O:29])[CH2:48][CH2:49]2)=[C:36]([C@@H:38]([NH:40][C:41](=[O:43])[CH3:42])[CH3:39])[CH:37]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68520135(1R,2R,4R)-2-(2,4-difluorophenyl)-4-(dimethylamino)cyclopentanecarboxylic acid hydrochlorideHCID 68520212N-[(1S)-1-(5-chloro-2-piperidin-4ylphenyl)ethyl]acetamide hydrochloride

Product 1

HCID 68516348N-{(1S)-1-[5-chloro-2-(1-{[(1R,2R,4R)-2-(2,4-difluorophenyl)-4-(dimethylamino)cyclopentyl]carbonyl}piperidin-4-yl)phenyl]ethyl}acetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

N,N-diisopropylethylamine (82.4 μL, 0.473 mmol) was added to a stirred suspension of (1R,2R,4R)-2-(2,4-difluorophenyl)-4-(dimethylamino)cyclopentanecarboxylic acid hydrochloride (48.2 mg, 0.158 mmol, prepared essentially as described in EXAMPLE 44), N-[(1S)-1-(5-chloro-2-piperidin-4-ylphenyl)ethyl]acetamide hydrochloride (50 mg, 0.158 mmol), and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (72.0 mg, 0.189 mmol) in N,N-dimethylformamide (1.5 mL) at ambient temperature. After approximately 18 h, the reaction mixture was poured into water and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification of the crude residue by preparative reversed phase high pressure liquid chromatography on YMC Pack Pro C18 phase (gradient elution; 0–100% acetonitrile/water as eluent, 0.1% TFA modifier) afforded the title compound as a buff white solid (m/z (ES) 532 (MH+).

Workup

  1. customprepared essentially
  2. customat ambient temperature
  3. extractionextracted three times with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customPurification of the crude residue by preparative reversed phase high pressure liquid chromatography on YMC Pack Pro
  8. washC18 phase (gradient elution; 0–100% acetonitrile/water as eluent, 0.1% TFA modifier)

Sources & evidence

ORD record
ord-dfdedfa77a824990bf56787fe1d893dc
Source dataset
uspto-grants-2006_03
Patent number
US07012084B2

Reaction notes

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