Methyl isonipecotate → HCID 44250958, compound

HRID 1256354Notes

Reaction equation

HRID 1256354 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9](C)[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[NH:25]1[CH2:30][CH2:29][CH:28]([C:31]([O:33][CH3:34])=[O:32])[CH2:27][CH2:26]1>O1CCOCC1.CS(C)=O.CO>[OH:23][C:20]([C:17]1[CH:16]=[CH:15][C:14]([C:13]([NH:12][C:4]2[CH:3]=[C:2]([N:25]3[CH2:30][CH2:29][CH:28]([C:31]([O:33][CH3:34])=[O:32])[CH2:27][CH2:26]3)[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=2)=[O:24])=[CH:19][CH:18]=1)([CH3:22])[CH3:21]

Participants

6

Reactant 2

HCID 424914Methyl isonipecotateHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 44250958HCID 44250958, compoundYield 28%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideCatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 500 mg, 1.51 mmol) and methyl piperidine-4-carboxylate (390 mg, 3.05 mmol) in Dioxane (15 mL) was stirred at 100° C. overnight. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, and was then purified by preparatory HPLC, 30-40% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (75 mg, 28%). 1H NMR (DMSO-d6) δ: 10.89 (s, 1H), 8.09 (d, J=2.3 Hz, 1H), 8.00 (d, J=8.6 Hz, 2H), 7.60 (d, J=8.6 Hz, 2H), 7.44 (s, 1H), 6.35 (d, J=2.3 Hz, 1H), 5.18 (s, 1H), 4.29-4.44 (m, 2H), 3.65 (s, 3H), 3.17 (d, J=5.3 Hz, 2H), 2.67-2.82 (m, 1H), 1.98-2.11 (m, 2H), 1.70-1.88 (m, 2H), 1.46 (s, 6H). ESI-MS: m/z 438.0 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC, 30-40% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-6f43267f6ecb44bcb8ff407ee6a96333
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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