2-Dimethylaminopyridine → HCID 53327927, compound

HRID 875021Notes

Reaction equation

HRID 875021 reaction equation
CN(C1C=CC=CN=1)C.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[NH:32]1[CH2:35][CH:34]([CH2:36][C:37]2[S:38][CH:39]=[C:40]([C:42]3[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=3)[N:41]=2)[CH2:33]1.[F:49][C:50]([F:66])([F:65])[C:51]1[O:55][N:54]=[C:53]([C:56]2[CH:57]=[C:58]([CH:62]=[CH:63][CH:64]=2)[C:59](O)=[O:60])[N:52]=1>CN(C=O)C>[F:48][C:45]1[CH:46]=[CH:47][C:42]([C:40]2[N:41]=[C:37]([CH2:36][CH:34]3[CH2:35][N:32]([C:59]([C:58]4[CH:62]=[CH:63][CH:64]=[C:56]([C:53]5[N:52]=[C:51]([C:50]([F:65])([F:49])[F:66])[O:55][N:54]=5)[CH:57]=4)=[O:60])[CH2:33]3)[S:38][CH:39]=2)=[CH:43][CH:44]=1

Participants

7

Reactant 5

HCID 218852-DimethylaminopyridineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 251808543-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acidHCID 67323950HCID 67323950, compound

Product 1

HCID 53327927HCID 53327927, compoundYield 46.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Dimethylaminopyridine (0.151 g, 1.24 mmol), EDCl (0.142 g, 0.744 mmol), and HOBt (0.095 g, 0.620 mmol) were added to a solution of 2-(azetidin-3-ylmethyl)-4-(4-fluorophenyl)thiazole (0.170 g, 0.682 mmol) in DMF (10.0 mL), followed by 3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid (0.160 g, 0.62 mmol). The reaction was stirred at room temperature for 2 h and concentrated under reduced pressure. The residue was diluted with EtOAc, washed with water and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure to yield the crude product which was purified by preparative thin layer chromatography using (40% EtOAc/Hexane) to provide (3-((4-(4-fluorophenyl)thiazol-2-yl)methyl)azetidin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone (0.140 g, 42.04%) 1H NMR (400 MHz, DMSO) δ 8.21 (s, 1H), 8.15-8.17 (d, 1H), 7.94-7.95 (d, 1H), 7.90-7.92 (m, 2H), 7.86-7.88 (d, 1H), 7.66-7.78 (t, 1H), 7.19-7.23 (t, 2H), 4.48-4.52 (t, 1H), 4.17-4.25 (m, 2H), 3.91-3.95 (m, 1H), 3.42-3.43 (m, 2H), 3.10-3.17 (m, 1H). MS (ESI) m/z: Calculated for C23H16F4N4O2S: 488.09. found: 489.0 (M+H)+

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was diluted with EtOAc
  3. washwashed with water and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto yield the crude product which
  7. customwas purified by preparative thin layer chromatography

Sources & evidence

ORD record
ord-376a1d8f3d1c47ee82cb27f0a987a76f
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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