Hydrochloric Acid → HCID 67980639, compound

HRID 2407029Notes

Reaction equation

HRID 2407029 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[CH:13][C:12]([CH:15]([NH:19][C:20]3[CH:29]=[CH:28][C:23]([C:24](OC)=[O:25])=[CH:22][N:21]=3)[CH2:16][CH2:17][CH3:18])=[CH:11][N:10]=2)=[CH:5][CH:4]=1.[Li+].[OH-].Cl.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:60][CH2:61][CH2:62][C:63]([O:65][CH3:66])=[O:64].C(N(CC)C(C)C)(C)C>C1COCC1.[NH4+].[Cl-]>[F:31][C:2]([F:1])([F:30])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[CH:13][C:12]([CH:15]([NH:19][C:20]3[CH:29]=[CH:28][C:23]([C:24]([NH:60][CH2:61][CH2:62][C:63]([O:65][CH3:66])=[O:64])=[O:25])=[CH:22][N:21]=3)[CH2:16][CH2:17][CH3:18])=[CH:11][N:10]=2)=[CH:5][CH:4]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68081111HCID 68081111, compound

Product 1

HCID 67980639HCID 67980639, compoundYield 107.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (+/−)-methyl 6-(1-(2-(4-(trifluoromethyl)phenyl)pyrimidin-5-yl)butylamino)nicotinate (796 mg, 1.85 mmol) in THF (10 mL) was added 2N aqueous LiOH (8 mL, 16 mmol). The mixture was stirred at 50° C. overnight. The mixture was neutralized by addition of 1N aqueous HCl and extracted with ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The residue was dissolved in DMF (5 mL). HATU (1.026 g, 2.7 mmol) was added. The mixture was stirred for 45 min. Methyl 3-aminopropanoate hydrochloride (373 mg, 2.7 mmol) and N,N-diisopropylethylamine (930 mg, 7.2 mmol) were added. The resulting mixture was stirred at room temperature for 2 h. The mixture was diluted with aqueous NH4Cl. The organic layer was washed with water, dried over Na2SO4, and concentrated under reduced pressure to give crude (+/−)-methyl 3-(6-(1-(2-(4-(trifluoromethyl)phenyl)pyrimidin-5-yl)butylamino)nicotinamido)propanoate (1.0 g). Resolution by SFC (Column: OJ 250 mm*20 mm*20 μm, Mobile phase: 75:25 CO2:methanol, Flow rate: 80 mL/min, Modifier: 0.1% diethylamine) to give methyl 3-(6-(1-(2-(4-(trifluoromethyl)phenyl)pyrimidin-5-yl)butylamino)nicotinamido)propanoate, Isomer 1 (Retention time 0.959 min, 390 mg) and methyl 3-(6-(1-(2-(4-(trifluoromethyl)phenyl)pyrimidin-5-yl)butylamino)nicotinamido)propanoate, Isomer 2 (Retention time 1.87 min, 400 mg).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in DMF (5 mL)
  5. stirringThe mixture was stirred for 45 min
  6. stirringThe resulting mixture was stirred at room temperature for 2 h
  7. washThe organic layer was washed with water
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f2f17eae9159419885fca16d25af2f3d
Source dataset
uspto-grants-2014_08
Patent number
US08809342B2

Reaction notes

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