Trifluoroacetic acid → HCID 58292903, 화합물

HRID 1947951노트

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HRID 1947951 반응식
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:19]([F:22])([F:21])[F:20])=[CH:4][N:3]=1.[CH2:23]([O:25][P:26]([CH:31]([C:33]1[CH:38]=[CH:37][C:36]([NH2:39])=[CH:35][CH:34]=1)[OH:32])(=[O:30])[O:27][CH2:28][CH3:29])[CH3:24].[C:40](O)([C:42](F)(F)F)=O>CCO>[CH2:28]([O:27][P:26]([CH:31]([O:32][CH2:40][CH3:42])[C:33]1[CH:34]=[CH:35][C:36]([NH:39][C:2]2[N:7]=[C:6]([NH:8][C:9]3[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=3[C:11](=[O:12])[NH:13][CH3:14])[C:5]([C:19]([F:22])([F:21])[F:20])=[CH:4][N:3]=2)=[CH:37][CH:38]=1)(=[O:30])[O:25][CH2:23][CH3:24])[CH3:29]

참가 물질

5

반응물 3

HCID 6422Trifluoroacetic acidHCID 23061737Diethyl P-[(4-aminophenyl)hydroxymethyl]phosphonateHCID 866338612-((2-Chloro-5-(trifluoromethyl)pyrimidin-4-yl)amino)-N-methylbenzamide

생성물 1

HCID 58292903HCID 58292903, 화합물수율 12%

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
105 °C

실험 절차

Under N2, a solution of 2-{[2-chloro-5-(trifluoromethyl)pyrimidin-4-yl]amino}-N-methylbenzamide (40.0 mg, 0.12 mmol) and diethyl[(4-aminophenyl)(hydroxy)methyl]-phosphonate (37.6 mg, 0.15 mmol) in a mixture of TFA (28 uL, 0.36 mmol) and EtOH (0.5 mL) was stirred at 105° C. for 45 min in a Biotage microwave reactor. The solvents were removed under reduced pressure and to the residue was added sat. NaHCO3 (aq) (2 mL) and DCM (5 mL). Layers were separated and the aqueous layer was extracted with DCM (3×5 mL). The combined organic phases were dried over MgSO4, concentrated, and purified by silica gel chromatography (5% 7 N NH3 in MeOH in DCM) to afford the desired product as a white-colored solid (8.4 mg, yield: 12%). 1H NMR (CD3OD, 400 MHz): δ=1.22 (dt, J=0.8, 7.6 Hz, 6H), 1.30 (t, J=7.2 Hz, 3H), 2.90 (s, 3H), 3.47-3.57 (m, 2H), 3.95-4.15 (m, 4H), 4.72 (d, J=16.0 Hz, 1H), 7.18 (dt, J=1.2, 7.6 Hz, 1H), 7.35 (dd, J=2.0, 8.4 Hz, 2H), 7.49 (dd, J=1.6, 8.8 Hz, 1H), 7.63-7.65 (m, 3H), 8.34 (s, 1H), 8.45 (m, 1H). MS (ES+): m/z 582.17 [MH+] HPLC: tR=3.44 min (OpenLynx, polar—5 min).

후처리

  1. customThe solvents were removed under reduced pressure and to the residue
  2. additionwas added sat. NaHCO3 (aq) (2 mL) and DCM (5 mL)
  3. customLayers were separated
  4. extractionthe aqueous layer was extracted with DCM (3×5 mL)
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography (5% 7 N NH3 in MeOH in DCM)

출처 및 근거

ORD 기록
ord-62090c4927864e5dbc529843773c9c27
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399433B2

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