Diisopropylethylamine → tert-Butyl (2S)-2-{[({8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridin-3-yl}-carbonyl)amino]methyl}pyrrolidin-1-carboxylate trifluoroacetate

HRID 2275830Notes

Reaction equation

HRID 2275830 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:13]([C:17]([OH:19])=O)=[C:14]([CH3:16])[N:15]=2)[CH:9]=[C:10]([CH3:12])[CH:11]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[NH2:58][CH2:59][C@@H:60]1[CH2:64][CH2:63][CH2:62][N:61]1[C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66].O.[C:73]([OH:79])([C:75]([F:78])([F:77])[F:76])=[O:74]>CN(C=O)C>[F:76][C:75]([F:78])([F:77])[C:73]([OH:79])=[O:74].[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:13]([C:17]([NH:58][CH2:59][C@@H:60]3[CH2:64][CH2:63][CH2:62][N:61]3[C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66])=[O:19])=[C:14]([CH3:16])[N:15]=2)[CH:9]=[C:10]([CH3:12])[CH:11]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 1512533tert-Butyl (2S)-2-(aminomethyl)pyrrolidine-1-carboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22392675Trifluoroacetic acid waterHCID 867178848-[(2,6-Difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 86717912tert-Butyl (2S)-2-{[({8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridin-3-yl}-carbonyl)amino]methyl}pyrrolidin-1-carboxylate trifluoroacetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

75 mg of 8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid (Example 21A, 0.23 mmol, 1 equivalent), 90 mg of O-(7-azabenzotriazol-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (HATU, 0.24 mmol, 1.05 equivalents) and 88 mg of N,N-diisopropylethylamine (0.12 ml, 0.68 mmol, 3 equivalents) were initially charged in 1.4 ml of DMF and stirred at RT for 20 min. 50 mg (0.25 mmol, 1.1 equivalents) of tert-butyl (2S)-2-(aminomethyl)pyrrolidine-1-carboxylate were then added, and the mixture was stirred at RT overnight. The reaction solution was then diluted with water/TFA and purified by preparative HPLC (method: RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). This gave 143 mg (99% of theory; purity 98%) of the title compound.

Workup

  1. stirringthe mixture was stirred at RT overnight
  2. custompurified by preparative HPLC (method: RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)

Sources & evidence

ORD record
ord-7bee3a617e6d449e8539d0a0e813ce16
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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