Diisopropylethylamine → (3-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl)-1,4-diazepan-1-yl)methanone

HRID 874921Notes

Reaction equation

HRID 874921 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:15][CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[N:7][CH:8]=1.[F:18][C:19]([F:35])([F:34])[C:20]1[O:24][N:23]=[C:22]([C:25]2[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=2)[C:28](O)=[O:29])[N:21]=1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>ClCCl>[F:34][C:19]([F:18])([F:35])[C:20]1[O:24][N:23]=[C:22]([C:25]2[CH:26]=[C:27]([C:28]([N:12]3[CH2:13][CH2:14][CH2:15][N:9]([C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:16])[F:17])=[CH:8][N:7]=4)[CH2:10][CH2:11]3)=[O:29])[CH:31]=[CH:32][CH:33]=2)[N:21]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27607791-[5-(Trifluoromethyl)pyridin-2-yl]-1,4-diazepaneHCID 251808543-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid

Product 1

HCID 53259017(3-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl)-1,4-diazepan-1-yl)methanoneYield 14%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-(5-(Trifluoromethyl)pyridin-2-yl)-1,4-diazepane (60 mg, 0.23 mmol), 3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid (68 mg, 0.28 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCl) (89 mg, 0.46 mmol) were dissolved in dichloromethane (3 mL) at room temperature. Diisopropylethylamine (DIEA) (0.085 mL, 0.93 mmol) was then introduced at room temperature and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with dichloromethane (60 mL) and washed with water (1×20 mL) and brine (1×20 mL). The organic layer was then dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was then purified on Prep TLC (30% Ethyl Acetate:Hexanes) to give (3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl)-1,4-diazepan-1-yl)methanone (14 mg, 14% yield). 1H NMR (300 MHz, CDCl3) δ 8.41 (s, 1H), 8.19-8.06 (m, 2H), 7.88 (s, 1H), 7.66-7.44 (m, 2H), 6.55 (bs, 1H), 3.98-3.64 (m, 8H), 1.74 (m, 2H). MS (ESI) m/z: Calculated for C21H17F6N5O2S: 485.13. found: 486.1 (M+H)+.

Workup

  1. washwashed with water (1×20 mL) and brine (1×20 mL)
  2. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto give the crude product
  5. customThe crude product was then purified on Prep TLC (30% Ethyl Acetate:Hexanes)

Sources & evidence

ORD record
ord-695c0f2fb5664b2c9aa834a0230977e1
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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