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

HRID 2169551ノート

反応式

HRID 2169551 の反応式
[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

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 146659712,4-Dichloro-6-methylpyrimidin-5-amineHCID 45790954Morpholine-3-carboxylic acid hydrochloride

生成物 1

HCID 866700992-chloro-4-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one収率 4.1%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  1. temperatureThe mixture was subsequently cooled to room temperature
  2. additionpoured into ice
  3. temperaturewhile slowly warmed to room temperature
  4. filtrationThe mixture was subsequently filtered
  5. customthe filtrate was purified by preparatory HPLC
  6. customThe fractions were collected
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-6e6aae6d123647ebb86d7c8c77d153fd
出典データセット
uspto-grants-2015_06
特許番号
US09045496B2

反応ノート

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