Diisopropylethylamine → Methyl 4-[({7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]bicyclo[2.2.2]octane-1-carboxylate

HRID 1486342Notes

Reaction equation

HRID 1486342 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[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15]([OH:17])=O)=[C:10]2[CH:9]=[C:8]([CH3:19])[CH:7]=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][C:59]12[CH2:66][CH2:65][C:62]([C:67]([O:69][CH3:70])=[O:68])([CH2:63][CH2:64]1)[CH2:61][CH2:60]2>CN(C=O)C.C(#N)C.O>[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[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15]([NH:58][C:59]34[CH2:64][CH2:63][C:62]([C:67]([O:69][CH3:70])=[O:68])([CH2:61][CH2:60]3)[CH2:65][CH2:66]4)=[O:17])=[C:10]2[CH:9]=[C:8]([CH3:19])[CH:7]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 53426661Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylateHCID 117859510HCID 117859510, compound

Product 1

HCID 117859762Methyl 4-[({7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridin-3-yl}carbonyl)amino]bicyclo[2.2.2]octane-1-carboxylateYield 68.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 80 mg 7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid (75% purity, 0.181 mmol) from Example 4A, 76 mg of HATU (0.199 mmol) and 94 μl (0.542 mmol) of N,N-diisopropylethylamine in 0.54 ml of DMF was stirred at RT for 10 min Subsequently, 40 mg (0.217 mmol) of methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate were added and the mixture was stirred at RT overnight. The reaction mixture was admixed with water and acetonitrile and purified by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.05% formic acid). 62 mg of the target compound were obtained (70% of theory).

Workup

  1. stirringthe mixture was stirred at RT overnight
  2. custompurified by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.05% formic acid)

Sources & evidence

ORD record
ord-608f4e550d324ba7adc4392d21b6e094
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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