Trifluoroacetic acid → HCID 58292903、化合物

HRID 511383ノート

反応式

HRID 511383 の反応式
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.[NH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH:30]([P:32](=[O:39])([O:36][CH2:37][CH3:38])[O:33][CH2:34][CH3:35])[OH:31])=[CH:26][CH:25]=1.[C:40](O)([C:42](F)(F)F)=O>CCO>[CH2:40]([O:31][CH:30]([P:32](=[O:39])([O:33][CH2:34][CH3:35])[O:36][CH2:37][CH3:38])[C:27]1[CH:28]=[CH:29][C:24]([NH:23][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:25][CH:26]=1)[CH3:42]

参加物

5

反応物 3

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

生成物 1

HCID 58292903HCID 58292903、化合物収率 12%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
105 °C

実験手順

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, 6 H), 1.30 (t, J=7.2 Hz, 3 H), 2.90 (s, 3 H), 3.47-3.57 (m, 2 H), 3.95-4.15 (m, 4 H), 4.72 (d, J=16.0 Hz, 1 H), 7.18 (dt, J=1.2, 7.6 Hz, 1 H), 7.35 (dd, J=2.0, 8.4 Hz, 2 H), 7.49 (dd, J=1.6, 8.8 Hz, 1 H), 7.63-7.65 (m, 3 H), 8.34 (s, 1 H), 8.45 (m, 1 H). MS (ES+): m/z 582.17 [MH+]. HPLC: tR=3.44 min (OpenLynx, polar—5 min).

後処理

  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)

出典と根拠

ORDレコード
ord-2bde4af5eaba47cf95fef7e2d953b94b
出典データセット
uspto-grants-2015_08
特許番号
US09096624B2

反応ノート

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