4-Methylmorpholine → HCID 178521262, compound

HRID 2074113Notes

Reaction equation

HRID 2074113 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][C:7]2[N:11]([CH2:12][C:13]([OH:15])=O)[N:10]=[C:9]([C:16]3[N:17]=[CH:18][NH:19][CH:20]=3)[CH:8]=2)=[CH:4][CH:3]=1.[NH:23]1[CH2:28][CH2:27][CH2:26][C@@H:25]([OH:29])[CH2:24]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[N:11]([CH2:12][C:13]([N:23]3[CH2:28][CH2:27][CH2:26][C@@H:25]([OH:29])[CH2:24]3)=[O:15])[N:10]=[C:9]([C:16]3[N:17]=[CH:18][NH:19][CH:20]=3)[CH:8]=2)=[CH:21][CH:22]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27593343-Hydroxypiperidine, (R)-HCID 178525854HCID 178525854, compound

Product 1

HCID 178521262HCID 178521262, compoundYield 15.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of [5-(4-fluorobenzyl)-3-(1H-imidazol-4-yl)-1H-pyrazol-1-yl]acetic acid (0.5 g, 1.67 mmol), (R)-piperidin-3-ol (0.30 g, 2.50 mmol), EDCI (0.58 g, 3.0 mmol), HOBt (0.40 g, 3.0 mmol) and NMM (1.0 mL, 10.0 mmol) in DMF (15 mL) was stirred at room temperature overnight. The mixture was concentrated in vacuo and the residue was diluted with water (5 mL). The mixture was extracted with CH2Cl2 (3×5 mL) and the organics combined, washed with 1 N aq. NaOH (3×10 mL), water (3×5 mL) and brine (25 mL), dried over MgSO4 and evaporated. The residue was purified via column chromatography (silica gel, EtOAc/Petroleum ether 1:4) to yield crude material (201.0 mg), which was further purified via prep. HPLC to yield the title compound (100 mg, 15%) as a white solid. 1H NMR (400 MHz, MeOD): δ ppm 8.837 (s, 1H), 7.699 (s, 1 H), 7.303 (m, 2 H), 7.078 (m, 2 H), 6.337 (s, 1 H), 3.992-3.039 (m, 7 H), 1.994-1.400 (m, 4 H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionthe residue was diluted with water (5 mL)
  3. extractionThe mixture was extracted with CH2Cl2 (3×5 mL)
  4. washwashed with 1 N aq. NaOH (3×10 mL), water (3×5 mL) and brine (25 mL)
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customThe residue was purified via column chromatography (silica gel, EtOAc/Petroleum ether 1:4)
  8. customto yield crude material (201.0 mg), which
  9. customwas further purified via prep

Sources & evidence

ORD record
ord-f030163ca0e04ec4bb953bff2a8fe462
Source dataset
uspto-grants-2011_04
Patent number
US07919488B2

Reaction notes

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