Cyclopropanecarboxylic acid → HCID 91758313, compound

HRID 575534Notes

Reaction equation

HRID 575534 reaction equation
ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH:23]1([C:26]([OH:28])=O)[CH2:25][CH2:24]1.[NH2:29][C@@H:30]([CH3:50])[C:31]([N:33]1[CH2:38][CH2:37][CH:36]([CH2:39][CH2:40][C:41]2[C:42]([NH2:49])=[N:43][C:44]([CH3:48])=[N:45][C:46]=2[Cl:47])[CH2:35][CH2:34]1)=[O:32]>C1COCC1.CCOC(C)=O>[NH2:49][C:42]1[C:41]([CH2:40][CH2:39][CH:36]2[CH2:35][CH2:34][N:33]([C:31](=[O:32])[C@@H:30]([NH:29][C:26]([CH:23]3[CH2:25][CH2:24]3)=[O:28])[CH3:50])[CH2:38][CH2:37]2)=[C:46]([Cl:47])[N:45]=[C:44]([CH3:48])[N:43]=1

Participants

7

Reactant 4

HCID 15655Cyclopropanecarboxylic acidHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 118061026HCID 118061026, compound

Product 1

HCID 91758313HCID 91758313, compoundYield 78.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add 1-hydroxy-7-azabenzotriazole (281 mg, 2.03 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (430 mg, 2.21 mmol) to a slurry of cyclopropanecarboxylic acid (161 μL, 2.03 mmol), (2S)-2-amino-1-[4-[2-(4-amino-6-chloro-2-methyl-pyrimidin-5-yl)ethyl]-1-piperidyl]propan-1-one (600 mg, 1.84 mmol) in anhydrous THF (12 mL). Then add TEA (770 μL, 5.52 mmol) and stir the resulting mixture at RT for 12 h. Dilute the reaction mixture with EtOAc (10 mL), filter over diatomaceous earth, and concentrate the filtrate in vacuo. Purify the resulting residue by mass-guided HPLC reverse phase chromatography (Agilent® 1200 LCMS and MSD mass spectrometer, 75×30 mm Phenomenex Gemini-NX®, 5μ particle size column with a 10×20 mm guard, 12-46% ACN in 10 mM aqueous ammonium bicarbonate solution, pH 10, gradient over 9 min) to obtain the title compound as a colorless glass (572 mg, 78%). LC-ESMS m/z (35Cl/37Cl) 394.2/396.2 (M+H).

Workup

  1. filtrationfilter over diatomaceous earth
  2. concentrationconcentrate the filtrate in vacuo
  3. customPurify the resulting residue by mass-guided HPLC reverse phase chromatography (Agilent® 1200 LCMS and MSD mass spectrometer, 75×30 mm Phenomenex Gemini-NX®, 5μ particle size column with a 10×20 mm guard, 12-46% ACN in 10 mM aqueous ammonium bicarbonate solution, pH 10, gradient over 9 min)

Sources & evidence

ORD record
ord-3599dfc21332478c90ddd95bf21e08d7
Source dataset
uspto-grants-2015_05
Patent number
US09035051B1

Reaction notes

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