Glycolic Acid → HCID 67095296, compound

HRID 1471821Notes

Reaction equation

HRID 1471821 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[N:20][C:21]=3[NH2:23])[N:16]([C@@H:24]3[CH2:29][CH2:28][CH2:27][NH:26][CH2:25]3)[N:15]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:30](O)(=[O:33])[CH2:31][OH:32].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[NH2:23][C:21]1[N:20]=[CH:19][N:18]=[C:17]2[N:16]([C@@H:24]3[CH2:29][CH2:28][CH2:27][N:26]([C:31](=[O:32])[CH2:30][OH:33])[CH2:25]3)[N:15]=[C:14]([C:11]3[CH:10]=[CH:9][C:8]([O:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:13][CH:12]=3)[C:22]=12

Participants

6

Reactant 4

HCID 757Glycolic AcidHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 582232723-(4-Phenoxy-phenyl)-1-piperidin-3-yl-1H-pyrazolo[3,4-d]pyriMidin-4-ylaMine

Product 1

HCID 67095296HCID 67095296, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (R)-3-(4-phenoxyphenyl)-1-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (6) (38.62 g), glycolic acid (9.13 g) and triethylamine (27.90 mL) in THF (500 mL) stirring in an ice bath, was added HATU (45.63 g) in one portion. The reaction was allowed to warm up to room temperature and stirred overnight (16 hrs). Solvent was removed by rotoevaporation. The residue was diluted with dichloromethane (500 mL), washed with aqueous NaOH solution (10%, 300 mL). The solid was filtered off and the bi-layer system was separated. The organic layer was washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was triturated with acetonitrile (300 mL) with some heating and cooled to room temperature. The mixture was filtered after sitting at room temperature overnight (16 hrs) and filtered. The solid collected was washed with small amount of acetonitrile and dried under high vacuo to provide the title compound a white powder with slight pink color (34.8 g).

Workup

  1. stirringstirred overnight (16 hrs)
  2. customSolvent was removed by rotoevaporation
  3. additionThe residue was diluted with dichloromethane (500 mL)
  4. washwashed with aqueous NaOH solution (10%, 300 mL)
  5. filtrationThe solid was filtered off
  6. customthe bi-layer system was separated
  7. washThe organic layer was washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe residue was triturated with acetonitrile (300 mL) with some heating and
  12. temperaturecooled to room temperature
  13. filtrationThe mixture was filtered
  14. filtration(16 hrs) and filtered
  15. customThe solid collected
  16. washwas washed with small amount of acetonitrile
  17. customdried under high vacuo

Sources & evidence

ORD record
ord-55c236c1d3084c8fbba656489ac31e6c
Source dataset
uspto-grants-2015_04
Patent number
US09012463B2

Reaction notes

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