Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-formyl-pyrazol-1-yl]piperidine-1-carboxylate → Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-(1-hydroxyethyl)pyrazol-1-yl]piperidine-1-carboxylate

HRID 908468Notes

Reaction equation

HRID 908468 reaction equation
[CH3:1][Mg]Br.[NH2:4][C:5]1[N:10]=[CH:9][C:8]([C:11]2[C:12]([CH:29]=[O:30])=[N:13][N:14]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)[CH:15]=2)=[CH:7][C:6]=1[C:31]1[O:32][C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=1>O1CCCC1>[NH2:4][C:5]1[N:10]=[CH:9][C:8]([C:11]2[C:12]([CH:29]([OH:30])[CH3:1])=[N:13][N:14]([CH:16]3[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])[CH2:20][CH2:21]3)[CH:15]=2)=[CH:7][C:6]=1[C:31]1[O:32][C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=1

Participants

4

Reactant 2

HCID 86630148Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-formyl-pyrazol-1-yl]piperidine-1-carboxylateHCID 178418573HCID 178418573, compound

Product 1

HCID 67388061Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-(1-hydroxyethyl)pyrazol-1-yl]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Over a period of 1 minute at −10° C. under nitrogen, a solution of methylmagnesium bromide (1.287 ml, 1.4M in toluene) was added portionwise to a stirred solution of tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-formyl-pyrazol-1-yl]piperidine-1-carboxylate (0.44 g), dissolved in tetrahydrofuran (10 ml). The resulting solution was stirred at room temperature for 1 hour. The reaction mixture was allowed to warm to room temperature under stirring over a period of 1 hour, quenched with a saturated aqueous solution of ammonium chloride and extracted with dichloromethane (2×50 ml). The combined organic phases were washed with water (2×10 ml), dried over magnesium sulfate and concentrated to afford the crude product as a dark orange oil which solidified on standing. The product was purified by flash chromatography on silica gel eluting with 30 to 100% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-(1-hydroxyethyl)pyrazol-1-yl]piperidine-1-carboxylate (0.120 g) as a solid. NMR Spectrum: (DMSOd6) 1.42 (d, 3H), 1.43 (s, 9H), 1.79 (dd, 1H), 1.85 (dd, 1H), 2.01-2.08 (m, 2H), 2.93 (bs, 2H), 4.06 (bs, 2H), 4.28-4.38 (m, 1H), 4.77-4.87 (m, 1H), 5.22 (d, 1H), 7.40-7.48 (m, 2H), 7.64 (bs, 2H), 7.77 (dd, 1H), 7.84 (dd, 1H), 8.10 (s, 1H), 8.51 (d, 1H), 8.56 (d, 1H); Mass spectrum: M+H+ 505.

Workup

  1. temperatureto warm to room temperature
  2. stirringunder stirring over a period of 1 hour
  3. customquenched with a saturated aqueous solution of ammonium chloride
  4. extractionextracted with dichloromethane (2×50 ml)
  5. washThe combined organic phases were washed with water (2×10 ml)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customto afford the crude product as a dark orange oil which
  9. customThe product was purified by flash chromatography on silica gel eluting with 30 to 100% ethyl acetate in petroleum ether
  10. customThe solvent was evaporated to dryness

Sources & evidence

ORD record
ord-2d14f6f67d05486da34d596bf9f66ba7
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

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