Dimethylformamide → HCID 70558848, compound

HRID 2278800Notes

Reaction equation

HRID 2278800 reaction equation
[CH:1]1([C:6]2[CH:7]=[C:8]([CH:12]=[C:13]([O:15][CH3:16])[N:14]=2)[C:9]([OH:11])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C=O)C.[Cl:22][C:23]1[CH:24]=[C:25]([CH:30]=[C:31]([CH3:42])[C:32]=1[O:33][CH2:34][CH:35]([O:39][CH2:40][CH3:41])[O:36][CH2:37][CH3:38])[C:26](=[NH:29])[NH:27]O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CCN(C(C)C)C(C)C.CC(=O)OCC>[Cl:22][C:23]1[CH:24]=[C:25]([C:26]2[N:29]=[C:9]([C:8]3[CH:12]=[C:13]([O:15][CH3:16])[N:14]=[C:6]([CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)[CH:7]=3)[O:11][N:27]=2)[CH:30]=[C:31]([CH3:42])[C:32]=1[O:33][CH2:34][CH:35]([O:39][CH2:40][CH3:41])[O:36][CH2:37][CH3:38]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 584180372-Cyclopentyl-6-methoxyisonicotinic acidHCID 178467977HCID 178467977, compound2×

Product 1

HCID 70558848HCID 70558848, compoundYield 70.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 81531DiisopropylethylamineSolvent

Procedure

To a solution of 2-cyclopentyl-6-methoxy-isonicotinic acid (704 mg, 3.18 mmol) in DMF (5 mL) TBTU (1.43 g, 4.45 mmol) and Hünig's base is added. The mixture is stirred at rt for 15 min before 3-chloro-4-(2,2-diethoxyethoxy)-N-hydroxy-5-methylbenzimidamide (907 mg, 2.86 mmol) is added. Stirring is continued for 18 h before another portion of 3-chloro-4-(2,2-diethoxyethoxy)-N-hydroxy-5-methylbenzimidamide (503 mg, 1.59 mmol) and TBTU (510 mg, 1.59 mmol) is added. Stirring is continued for 4 h. The mixture is diluted with EA (100 mL) and washed with water (50 mL). The washing is extracted three times with EA (3×50 mL). The combined org. extracts are dried over MgSO4, filtered and concentrated. The residue is dissolved in dioxane (35 mL) and the resulting solution is stirred at 110° C. for 18 h. The solvent is evaporated and the crude product is purified by MPLC on silica gel eluting with heptane:EA 7:3 to give 3-(3-chloro-4-(2,2-diethoxyethoxy)-5-methylphenyl)-5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazole (1.01 g) as a yellow oil; LC-MS: tR=1.43 min, [M+H]+=502.29; 1H NMR (CDCl3): δ 8.06 (d, J=1.9 Hz, 1H), 7.92 (d, J=1.4 Hz, 1H), 7.50 (d, J=0.9 Hz, 1H), 7.29 (d, J=1.1 Hz, 1H), 4.94 (t, J=5.3 Hz, 1H), 4.08 (d, J=5.3 Hz, 2H), 4.02 (s, 3H), 3.77-3.86 (m, 2H), 3.64-3.73 (m, 2H), 3.19-3.29 (m, 1H), 2.44 (s, 3H), 2.08-2.14 (m, 2H), 1.83-1.94 (m, 4H), 1.71-1.77 (m, 2H), 1.28 (t, J=7.1 Hz, 6H).

Workup

  1. additionis added
  2. additionis added
  3. stirringStirring
  4. washwashed with water (50 mL)
  5. extractionThe washing is extracted three times with EA (3×50 mL)
  6. dry with materialextracts are dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe residue is dissolved in dioxane (35 mL)
  10. stirringthe resulting solution is stirred at 110° C. for 18 h
  11. customThe solvent is evaporated
  12. customthe crude product is purified by MPLC on silica gel eluting with heptane:EA 7:3

Sources & evidence

ORD record
ord-e6774b37abec475bba06bbad246a0782
Source dataset
uspto-grants-2015_09
Patent number
US09133179B2

Reaction notes

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