Acetic Acid → HCID 178452458, compound

HRID 2075772Notes

Reaction equation

HRID 2075772 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[C:11]([C:15]3[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=3[OH:22])=[N:12][NH:13][CH:14]=2)=[CH:4][CH:3]=1.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][O:33][CH2:32][C@H:31]1[C:36](O)=[O:37])=[O:29])([CH3:26])([CH3:25])[CH3:24].C(N=C=NC(C)C)(C)C.O[Li].O.C(O)(=O)C>ClCCl.O.C(OCC)(=O)C>[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][O:33][CH2:32][C@H:31]1[C:36](=[O:37])[NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[C:11]([C:15]3[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=3[OH:22])=[N:12][NH:13][CH:14]=2)=[CH:4][CH:3]=1)=[O:29])([CH3:26])([CH3:25])[CH3:24]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 12734DiisopropylcarbodiimideHCID 168937Lithium hydroxide, monohydrateHCID 1512537(3S)-4-(tert-Butoxycarbonyl)morpholine-3-carboxylic acidHCID 1785075482-[4-(4-Amino-phenylethynyl)-1H-pyrazol-3-yl]-4-chloro-phenol

Product 1

HCID 178452458HCID 178452458, compoundYield 71.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of compound 24A (930 mg, 3.0 mmol) and (S)-morpholine-3,4-dicarboxylic acid 4-tert-butyl ester (19A, 2.09 g, 9.0 mmol) in anhydrous dichloromethane (20 mL) was added N,N′-diisopropylcarbodiimide (DIPC, 1.4 mL, 9.0 mmol). The reaction mixture was stirred at rt overnight. Solvent was removed. To the residua were added THF (20 mL) and methanol (20 mL) and a solution of LiOH.H2O (1.0 g, 23.84 mmol) in water (10 mL). The mixture was stirred at rt for 2 h. It was then neutralized with acetic acid (1.36 mL, 23.84 mmol). The mixture was diluted with ethyl acetate (˜100 mL), washed with brine, and dried over sodium sulfate. It was filtered, concentrated and filtered again to remove diisopropylurea. The filtrate was purified with silica column chromatography eluting with dichloromethane/ethyl acetate (v/v 5/1, 3/1, 2/1, 1/1) to provide the title compound (28A, 1.12 g) as a yellowish solid in 71.3% yield. LCMS (ESI) m/z 587.15 (MNa+), 521.05 (MH+), 421.06; HPLC: tR=5.32 min.

Workup

  1. customSolvent was removed
  2. additionTo the residua were added THF (20 mL) and methanol (20 mL)
  3. stirringThe mixture was stirred at rt for 2 h
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationIt was filtered
  7. concentrationconcentrated
  8. filtrationfiltered again
  9. customto remove diisopropylurea
  10. customThe filtrate was purified with silica column chromatography
  11. washeluting with dichloromethane/ethyl acetate (v/v 5/1, 3/1, 2/1, 1/1)

Sources & evidence

ORD record
ord-adbb3e7842b04fda9aaad5fd9a282c7c
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Reaction notes

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