Diisopropylethylamine → HCID 53379102, compound

HRID 2360992Notes

Reaction equation

HRID 2360992 reaction equation
Cl.[CH:2]1([CH2:8][NH:9][C:10]([C:12]2([C:18]3[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=3)[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[O:11])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C(OC([NH:39][C@@H:40]([CH2:44][C:45]1[S:46][CH:47]=[CH:48][CH:49]=1)[C:41](O)=[O:42])=O)(C)(C)C.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH:2]1([CH2:8][NH:9][C:10]([C:12]2([C:18]3[CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[C:20]([C:28]([F:31])([F:29])[F:30])[CH:19]=3)[CH2:17][CH2:16][N:15]([C:41](=[O:42])[C@@H:40]([NH2:39])[CH2:44][C:45]3[S:46][CH:47]=[CH:48][CH:49]=3)[CH2:14][CH2:13]2)=[O:11])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27344843-(Thien-2-yl)-L-alanine, N-BOC protectedHCID 86657554HCID 86657554, compound

Product 1

HCID 53379102HCID 53379102, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(3,5-bis-trifluoromethylphenyl)-piperidine-4-carboxylic acid cyclohexylmethylamide hydrochloride (0.169 mmol; 0.08 g) in DMF (3 mL) was added (S)-2-tert-butoxycarbonylamino-3-thiophen-2-yl-propionic acid (0.203 mmol; 55.1 mg), N,N-diisopropyl-N-ethylamine (0.338 mmol; 0.059 mL) and HBTU (0.203 mmol; 77 mg), and the resulting mixture was stirred at room temperature for 20 min. The mixture was then purified via reverse phase HPLC and the desired fractions were combined and lyophilized. The resulting residue was dissolved in 1,4-dioxane (3 mL) and a 4N HCl solution in 1,4-dioxane (3 mL) was added. The resulting solution was stirred for 2 hours at room temperature and evaporated. The residue was triturated with diethyl ether to yield 1-(2-(S)-amino-3-thiophen-2-yl-propionyl)-4-(3,5-bis-trifluoromethylphenyl)-piperidine-4-carboxylic acid cyclohexylmethylamide as a hydrochloride salt.

Workup

  1. customThe mixture was then purified via reverse phase HPLC
  2. dissolutionThe resulting residue was dissolved in 1,4-dioxane (3 mL)
  3. additiona 4N HCl solution in 1,4-dioxane (3 mL) was added
  4. stirringThe resulting solution was stirred for 2 hours at room temperature
  5. customevaporated
  6. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-bb06337e2a834a76aa2aab502e9ed3ef
Source dataset
uspto-grants-2014_04
Patent number
US08686152B2

Reaction notes

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