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

HRID 709438

反応式

HRID 709438 の反応式
[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]

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
130 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-8daa09b225c0443fb61c802a6d203ab6
出典データセット
uspto-grants-2015_11
特許番号
US09181200B2

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