Hydrochloric Acid → HCID 52258441, compound

HRID 574690Notes

Reaction equation

HRID 574690 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6]([N:9]=[C:10]=[O:11])=[CH:5][CH:4]=1.[NH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21](=[O:27])[CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[CH2:17][CH2:16]1.C(C(CC)C(O)=O)C.Cl>C1COCC1>[CH2:25]([CH:22]([CH2:23][CH3:24])[C:21]([N:18]1[CH2:17][CH2:16][CH:15]([NH:14][C:10]([NH:9][C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:12])([F:13])[F:1])=[CH:8][CH:7]=2)=[O:11])[CH2:20][CH2:19]1)=[O:27])[CH3:26]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 69152-Ethylbutyric acidHCID 737684-(Trifluoromethyl)phenyl isocyanateHCID 201179801016511-94-6

Product 1

HCID 52258441HCID 52258441, compoundYield 55.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice cold solution of 4-(trifluoromethyl)phenyl isocyanate (56.1 mg, 0.3 mmol) in THF (1.5 ml) was added 1-(4-aminopiperidin-1-yl)-2-ethylbutan-1-one (59.4 mg, 0.3 mmol), prepared via Example 14 and Example 15 using 2-ethylbutanoic acid. The reaction mixture was allowed to warm to rt and stirred overnight. 1 M HCl aqueous solution was added followed by extraction with EtOAc. Flash chromatography eluted with 50:1 DCM:MeOH followed by recrystallization from acetone afforded desired compound (64 mg, 55%) as a white solid. Mp 207.9-209.3° C. 1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 7.57 (m, 4H), 6.40 (d, J=7.6 Hz, 1H), 4.28 (brd, J=12.4 Hz, 1H), 3.96 (brd, J=13.6 Hz, 1H), 3.78-3.70 (m, 1H), 3.18 (t, J=11.6 Hz, 1H), 2.82 (t, J=11.0 Hz, 1H), 2.67-2.60 (m, 1H), 1.89 (d, J=10.8 Hz, p 1H), 1.83 (d, J=10.4 Hz, 1H), 1.56-1.42 (m, 2H), 1.42-1.31 (m, 2H), 1.31-1.16 (m, 2H), 0.83-0.75 (m, 6H). F NMR (300 M Hz, DMSO-d6) −60.324 (s).

Workup

  1. extractionfollowed by extraction with EtOAc
  2. washFlash chromatography eluted with 50:1 DCM
  3. customMeOH followed by recrystallization from acetone

Sources & evidence

ORD record
ord-1425d08cea054c71b41cc8faa72f7855
Source dataset
uspto-grants-2015_05
Patent number
US09034903B2

Reaction notes

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