Ammonia → 6'-Bromo-5-methyl-5'',6''-dihydro-4''H-dispiro[imidazole-2,4'-chromene-2',3''-pyran]-4-amine

HRID 539357ノート

反応式

HRID 539357 の反応式
[Br:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1([CH2:12][CH2:11][CH2:10][O:9][CH2:8]1)[CH2:6][C:5]12[NH:20][C:19](=S)[C:18]([CH3:22])=[N:17]1.[NH3:23]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1([CH2:12][CH2:11][CH2:10][O:9][CH2:8]1)[CH2:6][C:5]12[N:20]=[C:19]([NH2:23])[C:18]([CH3:22])=[N:17]1

参加物

3

反応物 2

HCID 222Ammonia2 回HCID 86667276HCID 86667276、化合物

生成物 1

HCID 573861526'-Bromo-5-methyl-5'',6''-dihydro-4''H-dispiro[imidazole-2,4'-chromene-2',3''-pyran]-4-amine収率 43%

反応条件

温度
120 °C

実験手順

6′-Bromo-5-methyl-5″,6″-dihydro-4″H-dispiro[imidazole-2,4′-chromene-2′,3″-pyran]-4(3H)-thione (Example 45 Step 3, 319 mg, 0.84 mmol) was taken up in ammonia (7M in MeOH, 10 mL, 70.00 mmol) and the resulting mixture was heated in the microwave reactor at 120° C. for 2 h. The solvent was evaporated and ammonia (7M in MeOH, 10 mL, 70.00 mmol) was added and the reaction was heated using MW for 1 h at 120° C. The solvent was evaporated and the resulting residue was taken up in DCM and saturated NaHCO3 and poured into a phase separator. The organic phase was dried and concentrated. The crude product was purified by flash chromatography using a gradient of 0-100% EtOAc in heptane followed by a gradient of 0-40% MeOH with 1% NH3 in DCM. The desired fractions were evaporated to give the title compound (130 mg, 43% yield) as a mixture of diastereomers in a 1:1 ratio as determined by NMR: 1H NMR (500 MHz, DMSO-d6) δ ppm 1.41-1.49 (m), 1.76-1.89 (m), 1.89-1.95 (m), 1.95-2.06 (m), 2.21 (s), 2.23 (s), 3.16 (m), 3.41 (d), 3.51 (dd), 3.69 (dd), 3.92 (t), 4.07-4.12 (m), 6.45 (d), 6.47 (d), 6.57 (br. s.), 6.61 (br. s.), 6.82 (d), 7.25 (d), 7.26 (d); MS (ES+) m/z 366.0 [M+H]+.

後処理

  1. customThe solvent was evaporated
  2. temperaturethe reaction was heated
  3. customfor 1 h
  4. customat 120° C
  5. customThe solvent was evaporated
  6. additionsaturated NaHCO3 and poured into a phase separator
  7. customThe organic phase was dried
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography
  10. customThe desired fractions were evaporated

出典と根拠

ORDレコード
ord-8685ea6bb6db483aadcb335c2e1c20b7
出典データセット
uspto-grants-2014_10
特許番号
US08865911B2

反応ノート

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