Proton sponge → (S)-3-isopropyl-6-((1-(o-tolyl)ethyl)amino)pyrimidine-2,4(1H,3H)-dione

HRID 709438

반응식

HRID 709438 반응식
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:8]([NH2:10])[CH3:9].CN(C1C2C(N(C)C)=CC=CC=2C=CC=1)C.Cl[C:28]1[NH:33][C:32](=[O:34])[N:31]([CH:35]([CH3:37])[CH3:36])[C:30](=[O:38])[CH:29]=1>CN1C(=O)CCC1.CS(C)=O>[CH:35]([N:31]1[C:30](=[O:38])[CH:29]=[C:28]([NH:10][C@H:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[CH3:1])[CH3:9])[NH:33][C:32]1=[O:34])([CH3:37])[CH3:36]

참가 물질

6

반응물 3

HCID 88675Proton spongeHCID 197800(alphaS)-alpha,2-DimethylbenzenemethanamineHCID 8201076-Chloro-3-(propan-2-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione

생성물 1

HCID 117764102(S)-3-isopropyl-6-((1-(o-tolyl)ethyl)amino)pyrimidine-2,4(1H,3H)-dione수율 8.1%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
130 °C

실험 절차

To a stirred solution of (1S)-1-(2-methylphenyl)ethan-1-amine (310 mg, 2.29 mmol, 1.50 equiv) in NMP (1 mL) was added proton sponge (491.4 mg, 2.30 mmol, 1.50 equiv) and 1.3 (288 mg, 1.53 mmol, 1.00 equiv). The resulting solution was stirred for 1 h at 130° C. in an oil bath, cooled to room temperature, and then diluted with DMSO (2 mL). The solids were filtered and the filtrate was purified by Flash-Prep-HPLC with the following conditions: Column: X Bridge C18, 19*150 mm, 5 um; Mobile Phase A: H2O/0.05% TFA, Mobile Phase B: CH3CN; Flow rate: 20 mL/min; Gradient: 30% B to 70% B in 10 min. This afforded 50 mg of crude product which was subsequently separated by chiral preparative HPLC with the following conditions: Column, Chiralpak IC, 2*25 cm, Sum; mobile phase, hexanes and ethanol (9:1, 15 min). This resulted in 35.6 mg (8%) of the title compound as a white solid. LC/MS: m/z (ES+) 288 (M+H)+. 1H-NMR (300 MHz, DMSO-d6): δ ppm 9.76 (br s, 1H), 7.28 (d, J=7.2 Hz, 1H) 7.24-7.14 (m, 3H), 6.48 (d, J=6.3 Hz, 1H), 4.95-4.86 (m, 1H), 4.60 (quin, J=6.9 Hz, 1H), 4.19 (s, 1H), 2.34 (s, 3H), 1.37 (d, J=6.6 Hz, 3H), 1.27 (d, J=6.9 Hz, 6H).

후처리

  1. temperaturecooled to room temperature
  2. filtrationThe solids were filtered
  3. customthe filtrate was purified by Flash-Prep-HPLC with the following conditions
  4. waitGradient: 30% B to 70% B in 10 min
  5. customThis afforded 50 mg of crude product which was subsequently separated by chiral preparative HPLC with the following conditions
  6. custommobile phase, hexanes and ethanol (9:1, 15 min)

출처 및 근거

ORD 기록
ord-8daa09b225c0443fb61c802a6d203ab6
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181200B2

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