Dimethylformamide → (R)-N-{1-[8-Acetyl-3-(4-ethoxy-phenyl)-4-oxo-3,4,5,6,7,8-hexahydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl}-N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-2-(4-fluoro-3-trifluoromethyl-phenyl)-acetamide

HRID 2223148노트

반응식

HRID 2223148 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].C(Cl)(=O)C(Cl)=O.CN(C)C=O.[C:27]([N:30]1[C:35]2[N:36]=[C:37]([C@H:50]([NH:52][CH2:53][C:54]3[N:55]([CH3:60])[N:56]=[C:57]([CH3:59])[CH:58]=3)[CH3:51])[N:38]([C:41]3[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH3:49])=[CH:43][CH:42]=3)[C:39](=[O:40])[C:34]=2[CH2:33][CH2:32][CH2:31]1)(=[O:29])[CH3:28].C(N(CC)CC)C>ClCCl>[C:27]([N:30]1[C:35]2[N:36]=[C:37]([C@H:50]([N:52]([CH2:53][C:54]3[N:55]([CH3:60])[N:56]=[C:57]([CH3:59])[CH:58]=3)[C:9](=[O:11])[CH2:8][C:5]3[CH:6]=[CH:7][C:2]([F:1])=[C:3]([C:12]([F:15])([F:14])[F:13])[CH:4]=3)[CH3:51])[N:38]([C:41]3[CH:42]=[CH:43][C:44]([O:47][CH2:48][CH3:49])=[CH:45][CH:46]=3)[C:39](=[O:40])[C:34]=2[CH2:33][CH2:32][CH2:31]1)(=[O:29])[CH3:28]

참가 물질

7

반응물 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27375934-Fluoro-3-(trifluoromethyl)phenylacetic acidHCID 58617388(R)-8-Acetyl-2-{1-[(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-amino]-ethyl}-3-(4-ethoxy-phenyl)-5,6,7,8-tetrahydro-3H-pyrido[2,3-d]pyrimidin-4-one

생성물 1

HCID 58617380(R)-N-{1-[8-Acetyl-3-(4-ethoxy-phenyl)-4-oxo-3,4,5,6,7,8-hexahydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl}-N-(2,5-dimethyl-2H-pyrazol-3-ylmethyl)-2-(4-fluoro-3-trifluoromethyl-phenyl)-acetamide수율 61.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

4-fluoro-3-trifluoromethylphenylacetic acid (45 mg, 0.20 mmol) was dissolved in dichloromethane and cooled to 0° C. Oxalyl chloride (18 μL, 0.20 mmol) was added, then after 5 min, dimethylformamide (1.6 μL, 0.02 mmol) was added. The reaction stirred at 0° C. for 30 min and room temperature for 1 h. The solution was added slowly to a mixture of D5 (55 mg, 0.12 mmol) and triethylamine (50 μL, 0.36 mmol) in dichloromethane at −78° C. This stirred for 30 min, then was washed with saturated aqueous sodium bicarbonate and brine. It was dried over magnesium sulfate, filtered, and concentrated in vacuo. Purified by reverse-phase HPLC to yield 49 mg of a colorless solid, 3. MS (MH+): 669.1. 1H NMR (500 MHz; CDCl3; T=298 K): δ 7.47-7.02 (m, 7H), 5.74-5.42 (m, 1H), 5.30-5.04 (m, 1H), 4.63-4.31 (m, 2H), 4.09-3.86 (m, 3H), 3.75-3.59 (m, 3H), 2.81-2.60 (m, 1H), 2.60-2.43 (m, 5H), 2.18 (m, 3H), 1.93 (broad s, 2H), 1.46 (t, 3H, J=6.7 Hz), 1.30 (t, 3H, J=7.7 Hz) ppm.

후처리

  1. stirringThis stirred for 30 min
  2. washwas washed with saturated aqueous sodium bicarbonate and brine
  3. dry with materialIt was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurified by reverse-phase HPLC

출처 및 근거

ORD 기록
ord-2965b68d220348299eb2aa2196a032ea
출처 데이터셋
uspto-grants-2008_05
특허 번호
US07375102B2

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