Diisopropylethylamine → (1S)-N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxamide

HRID 643527Notes

Reaction equation

HRID 643527 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][C:26]1[N:27]([CH:32]2[CH2:36][C@@:35]([CH:40]([CH3:42])[CH3:41])([C:37]([OH:39])=O)[CH:34]=[CH:33]2)[C:28]([CH3:31])=[CH:29][CH:30]=1.[C:43]([O:47][C:48]1[CH:55]=[CH:54][C:53]([C:56]([F:59])([F:58])[F:57])=[CH:52][C:49]=1[CH2:50][NH2:51])([CH3:46])([CH3:45])[CH3:44].C(N(C(C)C)C(C)C)C>CN(C=O)C.CCOC(C)=O>[C:43]([O:47][C:48]1[CH:55]=[CH:54][C:53]([C:56]([F:57])([F:58])[F:59])=[CH:52][C:49]=1[CH2:50][NH:51][C:37]([C@:35]1([CH:40]([CH3:42])[CH3:41])[CH2:36][CH:32]([N:27]2[C:28]([CH3:31])=[CH:29][CH:30]=[C:26]2[CH3:25])[CH:33]=[CH:34]1)=[O:39])([CH3:46])([CH3:44])[CH3:45]

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 431536542-Tert-butoxy-5-trifluoromethyl-benzylamineHCID 58617122(1S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylic acid

Product 1

HCID 58617139(1S)-N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxamideYield 120.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

HATU (33 g, 88.4 mmol) was added to a cooled (0° C.) mixture of (1S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylic acid (20 g, 80.3 mmol), [2-tert-butoxy-5-(trifluoromethyl)benzyl]amine (24 g, 96.4 mmol), and iPr2EtN (42 mL, 241 mmol) in DMF (400 mL). The resulting mixture was allowed to warm to r.t. and was stirred at r.t. for 18 hr. The reaction mixture was diluted with EtOAc and washed with brine (5×). The organic phase was then dried over sodium sulfate and evaporated to dryness. The dark oily residue was purified by column chromatography on silica gel eluting with hexane:EtOAc (7:3) to yield 46 g of (1S)—N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxamide as a yellow oil.

Workup

  1. temperaturea cooled
  2. washwashed with brine (5×)
  3. dry with materialThe organic phase was then dried over sodium sulfate
  4. customevaporated to dryness
  5. customThe dark oily residue was purified by column chromatography on silica gel eluting with hexane:EtOAc (7:3)

Sources & evidence

ORD record
ord-4407829f6ae947f0ab83e29c196e9f1d
Source dataset
uspto-grants-2010_04
Patent number
US07700591B2

Reaction notes

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