Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (S)-tert-butyl 4-((4-((3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl) carbamoyl)pyridin-2-yl)amino)piperidine-1-carboxylate

HRID 2202084Notes

Reaction equation

HRID 2202084 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:16]=[C:17]([CH:21]=[CH:22][N:23]=2)[C:18](O)=[O:19])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:48][CH2:49][C@H:50]([OH:62])[CH2:51][N:52]1[CH2:61][CH2:60][C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[CH2:53]1>C(Cl)Cl>[CH2:53]1[C:54]2[C:59](=[CH:58][CH:57]=[CH:56][CH:55]=2)[CH2:60][CH2:61][N:52]1[CH2:51][C@@H:50]([OH:62])[CH2:49][NH:48][C:18]([C:17]1[CH:21]=[CH:22][N:23]=[C:15]([NH:14][CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]2)[CH:16]=1)=[O:19]

Participants

5

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 25312355(S)-1-Amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-olHCID 902380262-((1-(Tert-butoxycarbonyl)piperidin-4-yl)amino)isonicotinic acid

Product 1

HCID 90241001(S)-tert-butyl 4-((4-((3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl) carbamoyl)pyridin-2-yl)amino)piperidine-1-carboxylateYield 53.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 2-((1-(tert-butoxycarbonyl)piperidin-4-yl)amino)isonicotinic acid (150 g, 0.47 mol) in DCM (1500 mL) was added HATU (178 g, 0.47 mol) and TEA (47 g, 0.47 mol) at 20° C., then the mixture was stirred at the temperature for 2 h. (S)-1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (113 g, 0.55 mol) was added to the solution, and the mixture was stirred at 20° C. for another 16 h, at which time TLC showed the completion of the reaction. The mixture washed with water (200 mL) and the combined organic phases were dried and concentrated. The residue was purified by flash chromatography (EtOAc˜DCM:MeOH=10:1) to give the title compound as yellowish oil. Four batches were run in parallel and produced a combined product weight of 510 g, yield: 53.2%. LCMS (m/z): 510.2 [M+H]+.

Workup

  1. additionwas added to the solution
  2. customthe completion of the reaction
  3. washThe mixture washed with water (200 mL)
  4. customthe combined organic phases were dried
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (EtOAc˜DCM:MeOH=10:1)

Sources & evidence

ORD record
ord-cab27e9d3a2f4581a3817320ba2fa109
Source dataset
uspto-grants-2016_06
Patent number
US09365519B2

Reaction notes

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