Acetic Acid → HCID 178451867, compound

HRID 2075769

Reaction equation

HRID 2075769 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]([N:30]1[CH2:35][CH2:34][CH2:33][CH2:32][C@H:31]1[C:36](O)=[O:37])([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].C(N=C=NC(C)C)(C)C.O[Li].O.C(O)(=O)C>ClCCl.O.C(OCC)(=O)C>[C:26]([O:25][C:23]([N:30]1[CH2:35][CH2:34][CH2:33][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:24])([CH3:29])([CH3:28])[CH3:27]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 12734DiisopropylcarbodiimideHCID 168937Lithium hydroxide, monohydrateHCID 688617(2S)-1-((tert-butoxy)carbonyl)piperidine-2-carboxylic acidHCID 1785075482-[4-(4-Amino-phenylethynyl)-1H-pyrazol-3-yl]-4-chloro-phenol

Product 1

HCID 178451867HCID 178451867, compoundYield 57.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of compound 24A (520 mg, 1.7 mmol) and N-Boc-2(S)-piperidinecarboxylic acid (8A) (584 mg, 2.55 mmol) in anhydrous dichloromethane (30 mL) was added N,N′-diisopropylcarbodiimide (DIPC, 0.4 mL, 2.55 mmol). The reaction mixture was stirred at rt overnight. The solvent was removed. To the residua were added THF (40 mL) and methanol (40 mL) and a solution of LiOH.H2O (2.0 g, 47.68 mmol) in water (20 mL). The mixture was stirred at rt for 3 h. It was then neutralized with acetic acid (3 mL, 52.41 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 hexanes/ethyl acetate (v/v 2/1, 3/2, 1/1) to provide the title compound (25A, 500 mg) as a yellowish solid in 57.2% yield. 1H NMR (CDCl3, 500 MHz) δ 10.62 (br s, 1H), 8.71 (d, 1H, J=2.0 Hz), 8.35 (br s, 1H), 7.84 (s, 1H), 7.55 (s, 4H), 7.22 (dd, 1H, J=9.0, 2.0 Hz), 6.99 (d, 1H, J=9.0 Hz), 4.90 (s, 1H), 4.05 (m, 1H), 2.90 (t, 1H, J=11.5 Hz), 2.35 (m, 1H), 1.80-1.30 (m, 16H). LCMS (ESI) m/z 587.15 (MNa+), 521.05 (MH+), 421.06; HPLC: tR=5.32 min.

Workup

  1. customThe solvent was removed
  2. additionTo the residua were added THF (40 mL) and methanol (40 mL)
  3. stirringThe mixture was stirred at rt for 3 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 hexanes/ethyl acetate (v/v 2/1, 3/2, 1/1)

Sources & evidence

ORD record
ord-9b8cbb0225dd473282649b4480a9deca
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Linked notes

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