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 2223148Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2223148
[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]

Komponenten

7

Edukt 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

Produkt 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)-acetamideAusbeute 61,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-2965b68d220348299eb2aa2196a032ea
Quelldatensatz
uspto-grants-2008_05
Patentnummer
US07375102B2

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