Hydrochloric Acid → 2-[2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}Piperidin-4-yl)-5-Chlorophenyl]-N-Methylacetamide

HRID 2415545Notes

Reaction equation

HRID 2415545 reaction equation
[CH:1]([N:4](CC)C(C)C)(C)C.[C:10]([N:14]1[CH2:18][C@@H:17]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])[C@H:16]([C:27]([N:29]2[CH2:34][CH2:33][CH:32]([C:35]3[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:36]=3[CH2:42][C:43](O)=[O:44])[CH2:31][CH2:30]2)=[O:28])[CH2:15]1)([CH3:13])([CH3:12])[CH3:11].CN.Cl.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[C:10]([N:14]1[CH2:18][C@@H:17]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])[C@H:16]([C:27]([N:29]2[CH2:30][CH2:31][CH:32]([C:35]3[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:36]=3[CH2:42][C:43]([NH:4][CH3:1])=[O:44])[CH2:33][CH2:34]2)=[O:28])[CH2:15]1)([CH3:12])([CH3:11])[CH3:13]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69717242[2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}Piperidin-4-yl)-5-Chlorophenyl]Acetic Acid

Product 1

HCID 693623392-[2-(1-{[(3S,4R)-1-Tert-Butyl-4-(2,4-Difluorophenyl)Pyrrolidin-3-yl]Carbonyl}Piperidin-4-yl)-5-Chlorophenyl]-N-Methylacetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N-diisopropylethylamine (0.166 mL, 0.953 mmol) was added to a stirred suspension of [2-(1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}piperidin-4-yl)-5-chlorophenyl]acetic acid (1-10) (40.0 mg), methylamine.HCl (42.9 mg, 0.635 mmol), O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (48.3 mg, 0.127 mmol) and 1-hydroxy-7-azabenotriazole (17.3 mg, 0.127 mmol) in N,N-dimethylformamide (0.65 mL) at ambient temperature. After approximately 18 h, the reaction mixture was poured into saturated aqueous sodium bicarbonate and extracted three times with ethyl acetate. The combined organic extracts were washed with water, brine, dried (Na2SO4) and concentrated in vacuo. Purification of the 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) gave 1-11 as a buff white solid (m/z (ES) 532 (MH+).

Workup

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

Sources & evidence

ORD record
ord-8d30d2dcf2144b6f998866b2a366a5e9
Source dataset
uspto-grants-2004_11
Patent number
US06818658B2

Reaction notes

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