1,2-Dichloroethane → tert-Butyl 4-((3-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methylphenyl)ethynyl)piperidine-1-carboxylate

HRID 1469170노트

반응식

HRID 1469170 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[C:15][C:16]2[CH:17]=[C:18]([N:26]([CH2:33][CH3:34])[CH:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[C:19]([CH3:25])=[C:20]([CH:24]=2)[C:21](O)=[O:22])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[Cl-].[CH3:43][C:44]1[CH:49]=[C:48]([CH3:50])[NH:47][C:46](=[O:51])[C:45]=1[CH2:52][NH3+:53].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CS(C)=O>[CH3:43][C:44]1[CH:49]=[C:48]([CH3:50])[NH:47][C:46](=[O:51])[C:45]=1[CH2:52][NH:53][C:21]([C:20]1[CH:24]=[C:16]([C:15]#[C:14][CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[CH:17]=[C:18]([N:26]([CH2:33][CH3:34])[CH:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[C:19]=1[CH3:25])=[O:22]

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 867155755-((1-(tert-Butoxycarbonyl)piperidin-4-yl)ethynyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoic acidHCID 178425248HCID 178425248, 화합물

생성물 1

HCID 86715576tert-Butyl 4-((3-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methylphenyl)ethynyl)piperidine-1-carboxylate수율 98%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

실험 절차

To a solution of 5-((1-(tert-butoxycarbonyl)piperidin-4-yl)ethynyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoic acid (1.06 g, 2.25 mmol) in DMSO (5.8 mL) at rt was added triethylamine (0.90 mL, 6.44 mmol) and (4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methanaminium chloride (0.405 g, 2.15 mmol). The clear solution become heterogenous. Then HOBT (0.493 g, 3.22 mmol) and EDC (0.617 g, 3.22 mmol) were added and the resulting reaction mixture was stirred at rt overnight. The reaction was quenched with water (80 mL) and the slurry was stirred for 1 h at rt. The slurry was filtrated and the cake was washed with water (2×20 mL). The collected solid was dried under vacuum to give the titled compound (1.27 g, 98% yield). 1H-NMR (500 MHz, CD3OD) 8 ppm; 7.22 (s, 1H), 7.08 (d, J=1.0 Hz 1H), 6.11 (s, 1H), 4.45 (s, 2H), 3.92 (brd, J=10.8 Hz, 2H), 3.78 (dd, J=4.4, 5.4 Hz, 1H), 3.75 (dd, J=4.4, 5.4 Hz, 1H), 3.36 (t, J=11.7 Hz, 2H), 3.21 (br t, J=8.3 Hz, 2H), 3.07 (q, J=7.3 Hz, 2H), 3.01 (dddd, J=3.9, 3.9, 11.3, 11.3 Hz, 1H), 2.84 (dddd, J=3.4, 3.4. 3.9, 3.9 Hz, 1H), 2.38 (s, 3H), 2.28 (s, 3H), 2.25 (s, 3H), 1.88 (m, 2H), 1.70 ((brd, J=12.2 Hz, 2H), 1.60 (m, 4H), 1.47 (s, 9H), 0.87 (t, J=7.3 Hz, 3H); MS (ESI) [M+H]+605.6.

후처리

  1. customthe resulting reaction mixture
  2. customThe reaction was quenched with water (80 mL)
  3. stirringthe slurry was stirred for 1 h at rt
  4. filtrationThe slurry was filtrated
  5. washthe cake was washed with water (2×20 mL)
  6. customThe collected solid was dried under vacuum

출처 및 근거

ORD 기록
ord-5732207f5e934a7cae706036e06652ed
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09006242B2

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