4-Methylmorpholine → 2-[5-[(4-Fluorophenyl)methyl]-3-(4-pyridinyl)-1H-pyrazol-1-yl]-1-[4-(methylsulfonyl)-1-piperidinyl]ethanone

HRID 2074084Notes

Reaction equation

HRID 2074084 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][C:7]2[N:11]([CH2:12][C:13]([OH:15])=O)[N:10]=[C:9]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH:8]=2)=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CN1CCOCC1.[CH3:52][S:53]([CH:56]1[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]1)(=[O:55])=[O:54]>CC(N(C)C)=O>[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][C:7]2[N:11]([CH2:12][C:13]([N:59]3[CH2:60][CH2:61][CH:56]([S:53]([CH3:52])(=[O:55])=[O:54])[CH2:57][CH2:58]3)=[O:15])[N:10]=[C:9]([C:16]3[CH:17]=[CH:18][N:19]=[CH:20][CH:21]=3)[CH:8]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 222750384-(Methanesulfonyl)piperidineHCID 670925255-[(4-fluorophenyl)methyl]-3-(4-pyridinyl)-1H-Pyrazole-1-acetic acid

Product 1

HCID 670918992-[5-[(4-Fluorophenyl)methyl]-3-(4-pyridinyl)-1H-pyrazol-1-yl]-1-[4-(methylsulfonyl)-1-piperidinyl]ethanone

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of [5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetic acid (150 mg, 0.48 mmol) in DMA (3 mL) at room temperature was added HOBt (72 mg, 0.53 mmol), EDCI (102 mg, 0.53 mmol), NMM (0.13 mL, 1.20 mmol) and 4-(methylsulfonyl)piperidine (117 mg, 0.72 mmol) and the mixture sonicated to a fine suspension and stirred for 18 hours at room temperature. The volatiles were removed under high vacuum and the residue partitioned between EtOAc (70 mL) and water (25 mL). The aqueous layer was removed and the organics washed with NaHCO3 (30 mL), brine (30 mL), dried over MgSO4, filtered and stripped to yield the title compound as an off-white solid, 144 mg, 66%. 1H NMR (400 MHz, DMSO-D6) δ ppm 8.46-8.56 (2 H, m), 7.60-7.71 (2 H, m), 7.25-7.37 (2 H, m), 7.07-7.19 (2 H, m), 6.53 (1 H, s), 5.10-5.41 (2 H, m), 4.40 (1 H, d, J=13.14 Hz), 3.97-4.15 (1 H, m), 3.95 (2 H, s), 3.34-3.49 (1 H, m), 3.12 (1 H, t, J=12.00 Hz), 2.96 (3 H, s), 2.64 (1 H, t, J=11.62 Hz), 2.06 (2 H, d, J=12.88 Hz), 1.59-1.79 (1 H, m), 1.36-1.54 (1 H, m); m/z (APCI+) for C23H25N4O3F 457.1 (M+H)+.

Workup

  1. customthe mixture sonicated to a fine suspension
  2. customThe volatiles were removed under high vacuum
  3. customthe residue partitioned between EtOAc (70 mL) and water (25 mL)
  4. customThe aqueous layer was removed
  5. washthe organics washed with NaHCO3 (30 mL), brine (30 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered

Sources & evidence

ORD record
ord-8527494472f1461bb2ebff0bae62cc25
Source dataset
uspto-grants-2011_04
Patent number
US07919488B2

Reaction notes

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