Hydrochloric Acid → 2-(4-Chloro-3-methoxy-phenyl)-8-[2-(4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-2,8-diaza-spiro[4.5]decan-1-one

HRID 2115297Notes

Reaction equation

HRID 2115297 reaction equation
C(O[C:6]([N:8]1[CH2:27][CH2:26][C:11]2([C:15](=[O:16])[N:14]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([O:24][CH3:25])[CH:18]=3)[CH2:13][CH2:12]2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.Cl.[Cl:29][C:30]1[C:31]([C:40]([F:43])([F:42])[F:41])=[N:32][N:33]([CH2:36]C(O)=O)[C:34]=1[CH3:35].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O1CCOCC1.CCOC(C)=O.CN(C=O)C>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([N:14]2[CH2:13][CH2:12][C:11]3([CH2:10][CH2:9][N:8]([C:6](=[O:7])[CH2:36][N:33]4[C:34]([CH3:35])=[C:30]([Cl:29])[C:31]([C:40]([F:42])([F:43])[F:41])=[N:32]4)[CH2:27][CH2:26]3)[C:15]2=[O:16])=[CH:18][C:19]=1[O:24][CH3:25]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 1876853(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59813962HCID 59813962, compound

Product 1

HCID 112376932-(4-Chloro-3-methoxy-phenyl)-8-[2-(4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-2,8-diaza-spiro[4.5]decan-1-one

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

2-(4-Chloro-3-methoxy-phenyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester ( 39.5 mg, 0.1 mmol, 1 equiv) was treated with 4 mL of 4N HCl in dioxane at rt for 1 h. The volatile was removed and to the residue were added 1 mL of DMF, (4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid (24.3 mg, 1 equiv), HATU (42 mg, 1.1 equiv), TEA (50 μL, 3 equiv). After stirring at rt over night, the mixture was taken up in EtOAc, washed with saturated sodium NaHCO3. Purification by reverse phase HPLC (acetonitrile-H2O with 0.1% TFA as eluent) gave 2-(4-Chloro-3-methoxy-phenyl)-8-[2-(4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-2,8-diaza-spiro[4.5]decan-1-one. LCMS observed for (M+H)+: 519. Retention time: 4.75 minutes (Agilent Zorbax SB-C18, 2.1×50 mm, 5μ, 35° C.) using a 4.5 minutes gradient of 20% to 95% B with a 1.1 minutes wash at 95% B (A=0.1 % formic acid/5% acetonitrile/94.9% water, B=0.1 % formic acid/99.9% acetonitrile).

Workup

  1. customThe volatile was removed and to the residue
  2. washwashed with saturated sodium NaHCO3
  3. customPurification by reverse phase HPLC (acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-fedd2bd9ba3a486d8872ddab22a18082
Source dataset
uspto-grants-2008_10
Patent number
US07435831B2

Reaction notes

Loading…