tert-Butanol → HCID 131726106, compound

HRID 723993Notes

Reaction equation

HRID 723993 reaction equation
Cl.[CH:2]1([NH:7][C:8]2[N:13]=[C:12]([C:14]3[C:15]([C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)=[N:16][N:17]4[CH:22]=[C:21](C(O)=O)[CH:20]=[CH:19][C:18]=34)[CH:11]=[CH:10][N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3]1.C([N:35]([CH2:38]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:47])C=CC=CC=1.[C:57]([OH:61])([CH3:60])([CH3:59])[CH3:58]>C(OCC)(=O)C>[CH:2]1([NH:7][C:8]2[N:13]=[C:12]([C:14]3[C:15]([C:26]4[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=4)=[N:16][N:17]4[CH:22]=[C:21]([NH:35][C:38](=[O:47])[O:61][C:57]([CH3:60])([CH3:59])[CH3:58])[CH:20]=[CH:19][C:18]=34)[CH:11]=[CH:10][N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 131726107HCID 131726107, compound

Product 1

HCID 131726106HCID 131726106, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)-pyrazolo[1,5-α]pyridine-6-carboxylic acid hydrochloride (60 mg, 0.13 mmol) in tertbutanol was added triethylamine (39 μL, 0.28 mmol) and diphenylphosphoryl azide (34 μL, 0.16 mmol). The reaction mixture was heated at reflux for 2.5 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic layer was washed with 5% aqueous citric acid solution, water, saturated aqueous sodium bicarbonate solution, and brine. The organic layer was dried over sodium sulfate. Filtration and concentration followed by flash chromatography (39:1 dichloromethane:methanol) provided tert-butyl 3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-6-ylcarbamate (35 mg, 540/%) as a light green oil. Rf 0.32 (29:1 dichloromethane:methanol); 1H NMR (400 MHz, CDCl3) δ 8.95 (br, 1H), 8.35 (d, 1H), 8.01 (br, 1H), 7.60 (m, 2H), 7.19 (d, 1H), 7.12 (t, 2H), 6.51 (s, 1H), 6.31 (d, 1H), 4.34 (m, 1H), 2.07 (m, 2H), 1.90–1.52 (m, 6H), 1.53 (s, 9H); MS m/z 489 (M+1).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2.5 hours
  3. washThe organic layer was washed with 5% aqueous citric acid solution, water, saturated aqueous sodium bicarbonate solution, and brine
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-ab96e2cba2994a39accf891e52e902c0
Source dataset
uspto-grants-2006_11
Patent number
US07141569B2

Reaction notes

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