2-Methylbenzoic acid → HCID 10181552, compound

HRID 1374700Notes

Reaction equation

HRID 1374700 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:18]([C:19]3[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=3)=[C:11]3[CH:12]=[C:13]([CH2:16][OH:17])[CH:14]=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:44][C:45]1[CH:53]=[CH:52][CH:51]=[CH:50][C:46]=1[C:47](O)=[O:48].N(C(OCC)=O)=NC(OCC)=O>C1COCC1.CCCCCC.C(OCC)(=O)C>[CH3:44][C:45]1[CH:53]=[CH:52][CH:51]=[CH:50][C:46]=1[C:47]([O:17][CH2:16][C:13]1[CH:14]=[CH:15][N:10]2[N:9]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[C:18]([C:19]3[CH:20]=[CH:21][N:22]=[CH:23][CH:24]=3)=[C:11]2[CH:12]=1)=[O:48]

Participants

7

Reactant 4

HCID 83732-Methylbenzoic acidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 99667962-(4-Fluorophenyl)-5-hydroxymethyl-3-(4-pyridinyl)-pyrazolo[1,5-a]pyridine

Product 1

HCID 10181552HCID 10181552, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

2-(4-Fluorophenyl)-5-hydroxymethyl-3-(4-pyridinyl)pyrazolo[1,5-a]pyridine (Example 6. 50 mg, 0.157 mmol), triphenyl phosphine (82 mg, 0.314 mmol) and 2-methylbenzoic acid (0.314 mmol) are dissolved in dry THF (3 mL). To the stirred solution is added diethyl azodicarboxylate (55 mg, 0.314 mmol) dropwise. The resulting solution is stirred at room temperature until reaction is complete as determined by TLC and then diluted with hexane/ethyl acetate (30 mL of a 1:1 mixture) and washed with water (×3). The organic phase is then shaken with dilute hydrochloric acid. In cases were the hydrochloride salt of the product deposits at this stage it is filtered off, washed with water and then hexane and dried. If no deposit is observed, the acidic phase is separated, washed once with hexane/ethyl acetate (15 mL of a 1:1 mixture) and basified with saturated sodium bicarbonate solution. This is then extracted with dichloromethane (15 mL) five times and the dichloromethane solution dried (MgSO4), filtered and concentrated to give the title compound. 1H NMR (d6-DMSO) δ 2.50 (s, 3H), 5.41 (s, 2H), 7.25–7.33 (m, 5H), 7.48 (t, J=7.4 Hz, 1H), 7.56 (dd, J=5.6, 8.5 Hz, 2H), 7.73 (d, J=5.8 Hz, 2H), 7.88 (d, J=7.9 Hz, 1H), 8.06 (s, 1H), 8.71 (d, J=6.2 Hz, 2H), 8.92 (d, J=7.1 Hz, 1H). APESI-MS m/z 438 (M+1)+.

Workup

  1. washwashed with water (×3)
  2. stirringThe organic phase is then shaken with dilute hydrochloric acid
  3. filtrationis filtered off
  4. washwashed with water
  5. dry with materialhexane and dried
  6. customthe acidic phase is separated
  7. washwashed once with hexane/ethyl acetate (15 mL of a 1:1 mixture) and
  8. extractionThis is then extracted with dichloromethane (15 mL) five times
  9. dry with materialthe dichloromethane solution dried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-c02643f6b45946a69ef7b098ad53efb1
Source dataset
uspto-grants-2007_01
Patent number
US07166597B2

Reaction notes

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