4-Methylmorpholine → HCID 86617956, compound

HRID 2074085Notes

Reaction equation

HRID 2074085 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][C:7]2[N:11]([CH2:12]C(O)=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.[CH:24]1[CH:25]=[CH:26][C:27]2N(O)N=[N:30][C:28]=2C=1.CCN=C=NCCCN(C)C.CN1CC[O:49][CH2:48]C1.[CH3:52][N:53](C1CCNCC1)[C:54](=[O:60])[O:55][C:56]([CH3:59])([CH3:58])[CH3:57]>CC(N(C)C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[N:11]([CH2:12][C:48]([N:30]3[CH2:24][CH2:25][CH:26]([CH2:52][NH:53][C:54](=[O:60])[O:55][C:56]([CH3:59])([CH3:58])[CH3:57])[CH2:27][CH2:28]3)=[O:49])[N:10]=[C:9]([C:16]3[CH:17]=[CH:18][N:19]=[CH:20][CH:21]=3)[CH:8]=2)=[CH:22][CH:23]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27568064-N-Boc-4-N-Methyl-aminopiperidineHCID 670925255-[(4-fluorophenyl)methyl]-3-(4-pyridinyl)-1H-Pyrazole-1-acetic acid

Product 1

HCID 86617956HCID 86617956, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a suspension of [5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetic acid (3.75 g, 12.06 mmol) in DMA (40 mL) at room temperature was added HOBt (1.79 g, 13.26 mmol), EDCI (2.54 g, 13.26 mmol), NMM (3.31 mL, 30.15 mmol) and tert-butyl methyl(piperidin-4-yl)carbamate (2.84 g, 13.26 mmol) and the mixture sonicated to a solution and stirred for 18 hours at room temperature. The volatiles were removed under high vacuum and the residue partitioned between EtOAc (300 mL) and water (100 mL). The aqueous layer was removed and the organics washed with NaHCO3 (100 mL), water (100 mL), brine (100 mL), dried over MgSO4, filtered and stripped to yield tert-butyl (1-{[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)methylcarbamate as a white solid. This was then taken into DCM (40 mL) and TFA (40 mL) added with stirring and the resulting solution stirred at ambient temperature for 18 hours. The volatiles were removed under vacuum and the residue suspended in DCM (200 mL) and 2 M NaOH added (200 mL) with stirring. The bi phasic solution was then stirred for 15 minutes and the phases separated. The organic layer was dried over MgSO4, filtered and stripped to yield the crude product which was then purified by Biotage flash chromatography (45 M cartridge), eluting with a DCM/MeOH/NH4OH gradient to afford the title compound as a white solid, 4.6 g, 94%. 1H NMR (400 MHz, DMSO-D6) δ ppm 8.52 (d, 2 H), 7.66 (d, 2 H), 7.29 (t, 2 H), 7.15 (t, 2 H), 6.51 (s, 1 H), 5.16 (q, 2 H), 4.04 (d, 1 H), 3.95 (s, 2 H), 3.79 (d, 1 H), 3.07-3.17 (m, 1 H), 2.76-2.89 (m, 1 H), 2.27 (s, 3 H), 1.71-1.86 (m, 2 H), 1.59-1.65 (m, 1 H), 1.18-1.31 (m, 1 H), 1.03-1.14 (m, 1 H); m/z (APCI+) for C23H26N5OF 408.2 (M+H)+.

Workup

  1. customthe mixture sonicated to a solution
  2. customThe volatiles were removed under high vacuum
  3. customthe residue partitioned between EtOAc (300 mL) and water (100 mL)
  4. customThe aqueous layer was removed
  5. washthe organics washed with NaHCO3 (100 mL), water (100 mL), brine (100 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered

Sources & evidence

ORD record
ord-82d6dd8499e141cb958edf3f3e6bdae7
Source dataset
uspto-grants-2011_04
Patent number
US07919488B2

Reaction notes

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