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

HRID 2169551Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([NH2:9])=[C:4]([CH3:10])[N:3]=1.Cl.[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH:13]1[C:18](O)=[O:19].CCN(C(C)C)C(C)C>CS(C)=O>[Cl:1][C:2]1[N:3]=[C:4]([CH3:10])[C:5]2[NH:9][C:18](=[O:19])[CH:13]3[CH2:14][O:15][CH2:16][CH2:17][N:12]3[C:6]=2[N:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A round-bottom flask was charged with crude 2,4-dichloro-6-methylpyrimidin-5-amine (6.644 g, 37.3 mmol), morpholine-3-carboxylic acid hydrochloride (7.51 g, 44.8 mmol), DIPEA (26.1 mL, 149 mmol) and DMSO (49.0 mL). The flask was heated overnight at 100° C. The mixture was subsequently cooled to room temperature and then poured into ice. The solution was stirred while slowly warmed to room temperature. The mixture was subsequently filtered, and the filtrate was purified by preparatory HPLC using a gradient of 15-40% CH3CN (with 0.035% TFA) in H2O (with 0.05% TFA). The fractions were collected and concentrated in vacuo to give the title compound as a white solid (387 mg, 4.1%). 1H NMR (400 MHz, DMSO-d6) δ 2.26 (s, 3 H), 2.54 (s, 1 H), 2.87-2.99 (m, 1 H), 3.43-3.52 (m, 1 H), 3.91 (dd, J=11.72, 3.42 Hz, 1 H), 4.10-4.22 (m, 2 H), 4.29 (dd, J=10.74, 3.91 Hz, 1 H), 10.51 (s, 1 H). ESI-MS m/z [M+H]+ calc'd for C10H11ClN4O2, 255.06; found 255.5.

Workup

temperatureThe mixture was subsequently cooled to room temperature
additionpoured into ice
temperaturewhile slowly warmed to room temperature
filtrationThe mixture was subsequently filtered
customthe filtrate was purified by preparatory HPLC
customThe fractions were collected
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-6e6aae6d123647ebb86d7c8c77d153fd
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09045496B2

Reaction notes

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