Acetic Acid → HCID 135974936, compound

HRID 2075751Notes

Reaction equation

HRID 2075751 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[C:11]([C:16]3[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][C:17]=3[OH:23])=[N:12][N:13]([CH3:15])[CH:14]=2)=[CH:4][CH:3]=1.[C:24]([N:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH:32]1[C:37](O)=[O:38])([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25].C(N=C=NC(C)C)(C)C.O.[OH-].[Li+].C(O)(=O)C>CN(C)C1C=CN=CC=1.ClCCl.O.C(OCC)(=O)C>[C:27]([O:26][C:24]([N:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH:32]1[C:37](=[O:38])[NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]#[C:9][C:10]2[C:11]([C:16]3[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][C:17]=3[OH:23])=[N:12][N:13]([CH3:15])[CH:14]=2)=[CH:6][CH:7]=1)=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

10

Reactant 5

HCID 176Acetic AcidHCID 12734DiisopropylcarbodiimideHCID 168937Lithium hydroxide, monohydrateHCID 5818311-[(Tert-butoxy)carbonyl]piperidine-2-carboxylic acidHCID 135508239HCID 135508239, compound

Product 1

HCID 135974936HCID 135974936, compoundYield 78.1%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-[4-(4-amino-phenylethynyl)-1-methyl-1H-pyrazol-3-yl]-4-methyl-phenol (1) (15.2 g, 50 mmol) and N-Boc-2-piperidinecarboxylic acid (2) (34.4 g, 150 mmol) and 4-dimethylaminopyridine (DMAP, 0.6 g, 5 mmol) in dry dichloromethane (600 mL) was added N,N′-diisopropylcarbodiimide (DIPC, 23.3 mL, 150 mmol) slowly. The reaction mixture was stirred at rt overnight. Water (˜100 mL) was added, and the mixture was stirred at rt for one hour. The organic layer was collected, filtered and concentrated. To the resultant residua was added THF (200 mL) and methanol (200 mL). A solution of lithium hydroxide monohydrate (21 g, 500 mmol) in water (100 mL) was slowly added above solution. The mixture was stirred at rt for 2 hours. It was then neutralized with acetic acid (29 mL, 500 mmol). The mixture was diluted with ethyl acetate (˜300 mL), and washed with brine, and dried over sodium sulfate. It was filtered, concentrated and purified with silica column chromatography eluting with dichloromethane-ethyl acetate (v/v 9/1). After crystallizing with hexanes/ethyl acetate, the title compound (3, 20.09 g) was obtained as white powder in 78% yield. 1H NMR (CDCl3, 500 MHz) δ 10.48 (s, 1H), 8.41 (s, 1H), 7.60 (s, 1H), 7.54 (d, 2H, J=8.0 Hz), 7.48 (d, 2H, J=8.0 Hz), 7.06 (d, 1H, J=8.0 Hz), 6.94 (d, 1H, J=8.0 Hz), 4.88 (br s, 1H), 4.08 (br s, 1H), 3.94 (s, 3H), 2.87 (t, 1H, J=6.1 Hz), 2.34 (s, 3H), 1.76-1.55 (m, 4H), 1.53 (s, 9H), 1.47 (m, 1H), 1.27 (m, 1H). LCMS (ESI) m/z 515.16 (MH+, 100), 415.15; HPLC: tR=6.88 min.

Workup

  1. stirringthe mixture was stirred at rt for one hour
  2. customThe organic layer was collected
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionTo the resultant residua was added THF (200 mL) and methanol (200 mL)
  6. stirringThe mixture was stirred at rt for 2 hours
  7. washwashed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationIt was filtered
  10. concentrationconcentrated
  11. custompurified with silica column chromatography
  12. washeluting with dichloromethane-ethyl acetate (v/v 9/1)
  13. customAfter crystallizing with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-c3287a7011ce42f5ae48b8f0a143ec3b
Source dataset
uspto-grants-2011_04
Patent number
US07923004B2

Reaction notes

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