Potassium Phosphate, Tribasic → ((2S,3R)-2-(((5-Cyclopropylpyridin-2-yl)amino)methyl)-3-methylpiperidin-1-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone

HRID 61058Notes

Reaction equation

HRID 61058 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][CH2:9][C@@H:10]2[C@H:15]([CH3:16])[CH2:14][CH2:13][CH2:12][N:11]2[C:17]([C:19]2[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][C:20]=2[N:26]2[N:30]=[CH:29][CH:28]=[N:27]2)=[O:18])=[N:6][CH:7]=1.[CH:31]1(B(O)O)[CH2:33][CH2:32]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.CC(O)=O.CC(O)=O.[Pd]>[CH:31]1([C:2]2[CH:3]=[CH:4][C:5]([NH:8][CH2:9][C@@H:10]3[C@H:15]([CH3:16])[CH2:14][CH2:13][CH2:12][N:11]3[C:17]([C:19]3[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][C:20]=3[N:26]3[N:30]=[CH:29][CH:28]=[N:27]3)=[O:18])=[N:6][CH:7]=2)[CH2:33][CH2:32]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 117727707HCID 117727707, compound

Product 1

HCID 117728315((2S,3R)-2-(((5-Cyclopropylpyridin-2-yl)amino)methyl)-3-methylpiperidin-1-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone

Reagents, catalysts & solvents 3

HCID 4144353Palladium (II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ((2S,3R)-2-(((5-bromopyridin-2-yl)amino)methyl)-3-methylpiperidin-1-yl)(5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone (0.052 g, 0.089 mmol), cyclopropylboronic acid (0.011 g, 1 mmol), Pd(Oac)2 (0.004 g, 0.018 mmol), tricyclohexylphosphine (0.01 g, 0.036 mmol) and K3PO4 (0.057 g, 0.267 mmol) in toluene (5 mL) and H2O (0.5 mL) was degassed, sealed and heated overnight at 100° C. in a microwave reactor. The reaction was filtered through a pad of diatomaceous earth, washing with EtOAc. The solvent was removed in vacuo and the crude was purified by reverse-phase preparative-HPLC to obtain the title compound. ESI-MS (m/z): 431 [M+1]+.

Workup

  1. customwas degassed
  2. customsealed
  3. filtrationThe reaction was filtered through a pad of diatomaceous earth
  4. washwashing with EtOAc
  5. customThe solvent was removed in vacuo
  6. customthe crude was purified by reverse-phase preparative-HPLC

Sources & evidence

ORD record
ord-9ebacd122e834c929b2fa87f12def3a0
Source dataset
uspto-grants-2016_09
Patent number
US09440982B2

Reaction notes

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