Ammonia → (S)-2-(1H-Benzo[d][1,2,3]triazol-1-yloxy)-4-(1-(5-fluoropyridin-2-yl)ethylamino) pyrimidine-5-carboxamide

HRID 573979Notes

Reaction equation

HRID 573979 reaction equation
Cl.C[N:3](C)CCCN=C=NCC.[OH:13][N:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=[N:15]1.Cl[C:24]1[N:29]=[C:28]([NH:30][C@H:31]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][N:34]=2)[CH3:32])[C:27]([C:40]([OH:42])=O)=[CH:26][N:25]=1.N>CN(C=O)C.O1CCOCC1>[N:14]1([O:13][C:24]2[N:29]=[C:28]([NH:30][C@H:31]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][N:34]=3)[CH3:32])[C:27]([C:40]([NH2:3])=[O:42])=[CH:26][N:25]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=[N:15]1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 89400397(S)-2-Chloro-4-(1-(5-fluoropyridin-2-yl)ethylamino)pyrimidine-5-carboxylic acid

Product 1

HCID 71245139(S)-2-(1H-Benzo[d][1,2,3]triazol-1-yloxy)-4-(1-(5-fluoropyridin-2-yl)ethylamino) pyrimidine-5-carboxamideYield 12.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

N-(3-Dimethylaminopropyl)-N′-ethyl carbodiimide hydrochloride (177 mg, 0.92 mmol) and 1-hydroxybenzotriazole (125 mg, 0.93 mmol) were added to a solution of (S)-2-chloro-4-(1-(5-fluoropyridin-2-yl)ethylamino)pyrimidine-5-carboxylic acid (Preparation 5b, 210 mg, 0.62 mmol) in N,N′-dimethylformamide (5 mL) and the mixture was stirred for 30 min at ambient temperature. 0.5M Ammonia solution in 1,4-dioxane (3 mL) was then added and the reaction mixture was stirred overnight at ambient temperature. The solvents were evaporated and the resulting residue was taken up in diethyl ether. The organic solution was washed with water and brine, dried (Na2SO4), filtered and the solvent evaporated under reduced pressure. The residue was purified by reverse phase chromatography (C-18 silica from Waters©, water/acetonitrile/methanol as eluents [0.1% v/v formic acid buffered] 0% to 100%) to yield the title compound (30 mg, 12%) as a solid.

Workup

  1. stirringthe reaction mixture was stirred overnight at ambient temperature
  2. customThe solvents were evaporated
  3. washThe organic solution was washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe residue was purified by reverse phase chromatography (C-18 silica from Waters©, water/acetonitrile/methanol as eluents [0.1% v/v formic acid

Sources & evidence

ORD record
ord-938c72a901b04bc787e2569bc7946a18
Source dataset
uspto-grants-2015_05
Patent number
US09034311B2

Reaction notes

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