Water → tert-butyl [2-chloro-5-({[1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)benzyl]carbamate

HRID 1500059Notes

Reaction equation

HRID 1500059 reaction equation
[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[CH3:19][N:20]1[C:24]([C:25](O)=[O:26])=[C:23]([C:28]([F:31])([F:30])[F:29])[C:22]([C:32]([F:38])([F:37])[C:33]([F:36])([F:35])[F:34])=[N:21]1.[NH2:39][C:40]1[CH:41]=[CH:42][C:43]([Cl:55])=[C:44]([CH:54]=1)[CH2:45][NH:46][C:47](=[O:53])[O:48][C:49]([CH3:52])([CH3:51])[CH3:50].O>C1COCC1>[Cl:55][C:43]1[CH:42]=[CH:41][C:40]([NH:39][C:25]([C:24]2[N:20]([CH3:19])[N:21]=[C:22]([C:32]([F:37])([F:38])[C:33]([F:35])([F:36])[F:34])[C:23]=2[C:28]([F:30])([F:31])[F:29])=[O:26])=[CH:54][C:44]=1[CH2:45][NH:46][C:47](=[O:53])[O:48][C:49]([CH3:50])([CH3:51])[CH3:52]

Participants

6

Reactant 4

HCID 962WaterHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 21077619Tert-butyl (5-amino-2-chlorobenzyl)carbamateHCID 866600921-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid

Product 1

HCID 131734263tert-butyl [2-chloro-5-({[1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)benzyl]carbamateYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride (=DMTMM, see Tetrahedron 1999, 55, 13159-13170) (1.25 g, 4.51 mmol, 1.1 eq.) was added to 1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (1.28 g, 4.1 mmol; preparation according to WO2010/051926) and tert-butyl (5-amino-2-chlorobenzyl)carbamate (1.05 g, 4.1 mmol, 1.0 eq.) in THF (15 ml), and the mixture was left at room temperature for 18 h. Water (30 ml) was added, the mixture was extracted with ethyl acetate (3×30 ml) and the extracts were dried over MgSO4. After concentration under reduced pressure, the product was purified by column chromatography on silica gel (hexane/ethyl acetate), giving tert-butyl [2-chloro-5-({[1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl}amino)benzyl]carbamate (924 mg, 41%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×30 ml)
  2. dry with materialthe extracts were dried over MgSO4
  3. concentrationAfter concentration under reduced pressure
  4. customthe product was purified by column chromatography on silica gel (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-cd729f0ec4364cedbaae3247b1a9251a
Source dataset
uspto-grants-2015_12
Patent number
US09204645B2

Reaction notes

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