Water → 2-chloro-5-(2-methyl-2-(tetrahydro-2H-pyran-2-yloxy)propyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

HRID 1696032Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([NH:9][CH2:10][C:11]([CH3:20])([O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[CH3:12])=[CH:4][N:3]=1.Cl.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH:23]1[C:28](O)=[O:29].C(N(C(C)C)CC)(C)C.O>CS(C)=O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:9]([CH2:10][C:11]([CH3:20])([O:13][CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][O:15]3)[CH3:12])[C:28](=[O:29])[CH:23]3[CH2:24][O:25][CH2:26][CH2:27][N:22]3[C:6]=2[N:7]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a mixture of 2,4-dichloro-N-(2-methyl-2-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrimidin-5-amine (315 mg, 0.982 mmol) and morpholine-3-carboxylic acid hydrochloride (247 mg, 1.47 mmol) in DMSO (6 ml) was added diisopropylethylamine (0.686 ml, 3.93 mmol), and the reaction mixture was stirred at 95° C. for 4 hours. The reaction mixture was poured into water and extracted with EtOAc. The organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give a crude oil. The crude residue was chromatographed by silica gel (hexane/ethyl acetate, 19:1 to 1:1) to afford 2-chloro-5-(2-methyl-2-(tetrahydro-2H-pyran-2-yloxy)propyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (96.2 mg, 0.242 mmol, 25% yield) as a pale yellow oil which was used in the next reaction without further purification. MS [M+H] found 397.

Workup

extractionextracted with EtOAc
dry with materialThe organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customto give a crude oil
customThe crude residue was chromatographed by silica gel (hexane/ethyl acetate, 19:1 to 1:1)

Sources & evidence

ORD record: ord-4ec27a7178d840aba6743ca7efeca091
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163755B2

Reaction notes

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