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

HRID 2169551노트

반응식

HRID 2169551 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-6e6aae6d123647ebb86d7c8c77d153fd
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045496B2

반응 노트

불러오는 중…