2-(4-Fluorophenyl)acetic acid → 2-(4-fluorophenyl)-N-{5-methyl-3-[4-(trifluoromethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-2-yl}acetamide

HRID 1912967Notes

Reaction equation

HRID 1912967 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.[CH3:12][C:13]1[CH:18]=[CH:17][N:16]2[N:19]=[C:20]([NH2:33])[C:21]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=3)=[C:15]2[N:14]=1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.N1C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([NH:33][C:20]2[C:21]([C:22]3[CH:23]=[CH:24][C:25]([O:28][C:29]([F:32])([F:30])[F:31])=[CH:26][CH:27]=3)=[C:15]3[N:14]=[C:13]([CH3:12])[CH:18]=[CH:17][N:16]3[N:19]=2)=[O:11])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 98372-(4-Fluorophenyl)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 687500215-Methyl-3-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-2-amine

Product 1

HCID 687516032-(4-fluorophenyl)-N-{5-methyl-3-[4-(trifluoromethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-2-yl}acetamide

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

4-Fluorophenylacetic acid (32 mg, 0.21 mmol) was added to a stirring solution of the product from Example 168A (20 mg, 0.065 mmol) in DMF (0.5 mL) and pyridine (0.5 mL). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (43 mg, 0.22 mmol) was added and stirring was continued at room temperature for 40 h. The reaction mixture was quenched by addition of MeOH (1 mL) and HOAc (0.1 mL) and stirred for 40 minutes. The solution was concentrated under vacuum, and the residue was purified by HPLC (30×100 mm XBridge column eluted with aqueous 0.1 M (NH4)2CO3-MeOH, 60:40-0:100 over 15 min) to provide the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.56 (s, 3H), 3.65 (s, 2H), 7.03 (d, J=7.1 Hz, 1H), 7.15 (t, J=8.8 Hz, 2H), 7.25 (d, J=8.5 Hz, 2H), 7.29-7.40 (m, 2H), 7.76 (d, J=8.8 Hz, 2H), 8.94 (d, J=7.1 Hz, 1H), 10.42 (s, 1H); MS (DCI/NH3) m/z 445 (M+H)+.

Workup

  1. customThe reaction mixture was quenched by addition of MeOH (1 mL) and HOAc (0.1 mL)
  2. stirringstirred for 40 minutes
  3. concentrationThe solution was concentrated under vacuum
  4. customthe residue was purified by HPLC (30×100 mm XBridge column eluted with aqueous 0.1 M (NH4)2CO3-MeOH, 60:40-0:100 over 15 min)

Sources & evidence

ORD record
ord-5c02937e9ca5435dbe5d12f86e55f22e
Source dataset
uspto-grants-2013_12
Patent number
US08609669B2

Reaction notes

Loading…