N-methyl-2-pyrrolidone → HCID 71227465, 화합물

HRID 715529노트

반응식

HRID 715529 반응식
[CH2:1]([N:3]1[C:7]([CH3:8])=[C:6]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:5]=[N:4]1)[CH3:2].[Li]CCCC.[CH3:22][C@:23]1([CH2:31][N:32]2[C:36]3[CH:37]=[C:38]([C:41]#[N:42])[CH:39]=[CH:40][C:35]=3[N:34]=[CH:33]2)CCC[C@:25]2(OC2)[CH2:24]1.CN1C(=O)CCC1>C1COCC1.O>[CH2:1]([N:3]1[C:7]([CH3:8])=[C:6]([N:9]2[CH2:13][C@@:12]3([CH2:15][CH2:25][CH2:24][C@@:23]([CH2:31][N:32]4[C:36]5[CH:37]=[C:38]([C:41]#[N:42])[CH:39]=[CH:40][C:35]=5[N:34]=[CH:33]4)([CH3:22])[CH2:14]3)[O:11][C:10]2=[O:16])[CH:5]=[N:4]1)[CH3:2]

참가 물질

7

반응물 4

HCID 13387N-methyl-2-pyrrolidoneHCID 86716577((3S,5S)-5-methyl-1-oxaspiro[2.5]octan-5-ylmethyl)-1H-benzo[d]imidazole-6-carbonitrileHCID 131734098HCID 131734098, 화합물HCID 178418339Butyllithium

생성물 1

HCID 71227465HCID 71227465, 화합물수율 38.9%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 1-ethyl-5-methyl-1H-pyrazol-4-amine, 2 hydrochloride (0.5 g, 2.52 mmol), Boc2O (0.703 ml, 3.03 mmol), TEA (1.055 mL, 7.57 mmol) and DMAP (10 mg, 0.082 mmol) in DCM (18.74 mL) was stirred at RT for 16 h. The mixture was then extracted with DCM, dried over Na2SO4 and filtered. The filtrate was concentrated and purified via silica gel chromatography (ISCO, 40 g column; 0-5% MeOH/DCM) to give tert-butyl (1-ethyl-5-methyl-1H-pyrazol-4-yl)carbamate as brown oil (300 mg, 52.8% yield). To a solution of tert-butyl (1-ethyl-5-methyl-1H-pyrazol-4-yl)carbamate (0.162 g, 0.719 mmol) in THF (1 mL) at −78° C. under N2 was added n-BuLi (2.5M in hexane) (0.27 ml, 0.675 mmol) dropwise. The mixture was allowed to warm up to RT and stirred for 20 min. 1-{[(3S,5S)-5-methyl-1-oxaspiro[2.5]oct-5-yl]methyl}-1H-benzimidazole-6-carbonitrile (0.15 g, 0.533 mmol) was then added followed by NMP (0.5 mL). The solution was then heated at 70° C. for 16 h. Water was then added to the reaction mixture and extracted with EtOAc. The organic layer was concentrated and purified via HPLC to give 1-(((5S,7S)-3-(1-ethyl-5-methyl-1H-pyrazol-4-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile as a white solid (89.6 mg, 38.9% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.47 (s, 1H), 8.38 (s, 1H), 7.83 (d, J=8.28 Hz, 1H), 7.59 (dd, J=1.51, 8.28 Hz, 1H), 7.41 (s, 1H), 4.16 (br. s., 2H), 4.03 (q, J=7.03 Hz, 2H), 3.54 (s, 2H), 2.14 (s, 3H), 1.95 (d, J=14.0 Hz, 1H), 1.86 (d, J=14.31 Hz, 1H), 1.61 (d, J=13.55 Hz, 3H), 1.31-1.51 (m, 3H), 1.28 (t, 3H), 1.06 (s, 3H). MS (m/z) 433.3 (M+H+).

후처리

  1. temperatureThe solution was then heated at 70° C. for 16 h
  2. extractionextracted with EtOAc
  3. concentrationThe organic layer was concentrated
  4. custompurified via HPLC

출처 및 근거

ORD 기록
ord-a8adcd2cc18b4e44bc07c10ca4628185
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187464B2

반응 노트

불러오는 중…