4-Aminomethyltetrahydropyran → HCID 44193423, compound

HRID 1850005Notes

Reaction equation

Br[C:2]([CH3:16])([CH3:15])[C:3]([NH:5][C:6]1ON=[C:8]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:7]=1)=[O:4].[O:17]1[CH2:22][CH2:21][CH:20]([CH2:23][NH2:24])[CH2:19][CH2:18]1.C(#[N:27])C.[OH2:28]>[Ag-]=O>[C:11]([C:8]1[O:28][N:27]=[C:6]([NH:5][C:3](=[O:4])[C:2]([CH3:16])([NH:24][CH2:23][CH:20]2[CH2:21][CH2:22][O:17][CH2:18][CH2:19]2)[CH3:15])[CH:7]=1)([CH3:14])([CH3:13])[CH3:12]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 2-bromo-N-(3-tert-butyl-isoxazol-5-yl)-2-methyl-propionamide (0.25 g, 0.87 mmol, prepared according to method C, step 1)) and 1-tetrahydro-2H-pyran-4-ylmethane-amine (0.20 g, 1.73 mmol) in acetonitrile/water (95/5, 4 mL) is added silver (I) oxide (0.80 g, 3.68 mmol). The reaction is heated to 60° C. for 18 h. After cooling, the reaction mixture is filtered through a plug of Na2SO4/cotton wool. The filtrate is concentrated under reduced pressure to give a brown oil, which is purified by mass-triggered preparative LC (neutral conditions) to afford N-(5-tert-butyl-isoxazol-3-yl)-2-methyl-2-[(tetrahydro-pyran-4-ylmethyl)-amino]-propionamide (28 mg, 10%). m/z 324 [M+H+]. The hydrochloride salt of the title compound is formed by trituration with 1M HCl solution in ether.

Workup

temperatureAfter cooling
filtrationthe reaction mixture is filtered through a plug of Na2SO4/cotton wool
concentrationThe filtrate is concentrated under reduced pressure
customto give a brown oil, which
customis purified by mass-triggered preparative LC (neutral conditions)

Sources & evidence

ORD record: ord-da87d428483d4b0db809074bbb5f3e69
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08957063B2

Reaction notes

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