Carbamimidoylazanium Chloride → HCID 178448652、化合物

HRID 733249ノート

反応式

HRID 733249 の反応式
CC(C)([O-])C.[K+].[Cl-].[NH2:8][C:9]([NH2:11])=[NH2+:10].[F:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:21]=1[CH:20]([CH2:22][C:23](OCC)=[O:24])[N:19]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:18]2=[O:32]>>[F:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:21]=1[CH:20]([CH2:22][C:23]([NH:10][C:9]([NH2:11])=[NH:8])=[O:24])[N:19]([CH2:28][CH:29]([CH3:30])[CH3:31])[C:18]2=[O:32]

参加物

4

反応物 3

HCID 5460839Carbamimidoylazanium ChlorideHCID 23665647Potassium tert-butoxideHCID 69713989Ethyl (7-fluoro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate

生成物 1

HCID 178448652HCID 178448652、化合物収率 21.4%

反応条件

温度
20 °C

実験手順

N-[(7-Fluoro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetyl]guanidine is prepared as described in Example 1, starting with 1.29 g of potassium tert-butoxide, 1.32 g of guanidinium chloride and 0.67 g of ethyl (7-fluoro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetate. The reaction mixture is stirred at a temperature in the region of 20° C. for 20 hours, and is then filtered. The filtrate is taken up in 40 cm3 of water and 60 cm3 of ethyl acetate. After separation of the phases by settling, the organic phase is separated out and the aqueous phase is extracted with twice 60 cm3 of ethyl acetate. The organic extracts are combined, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure (0.6 kPa) at a temperature in the region of 55° C. The evaporation residue is taken up in diethyl ether and concentrated to dryness again under the same conditions, and then taken up in water and concentrated to dryness again under the same conditions. The residue is purified by chromatography under argon pressure (50 kPa), on a column of silica gel (particle size 15-40 μm), eluting with a mixture of dichloromethane/methanol (90/10 by volume). The fractions comprising the expected product are combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 20° C. The residue is taken up in diisopropyl ether, triturated, filtered and then dried. 0.15 g of N-[(7-fluoro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetyl]guanidine is thus obtained in the form of a pale yellow solid melting at 205° C. 1H NMR (300 MHz, d6-(CD3)2SO, δ in ppm): 0.74 (d, J=6.5 Hz: 3H); 0.89 (d, J=6.5 Hz: 3H); 2.06 (mt: 1H); 2.38 (dd, J=15 and 7.5 Hz: 1H); 2.90 (dd, J=15 and 4.5 Hz: 1H); 3.04 (dd, J=13.5 and 4.5 Hz: 1H); 3.56 (dd, J=13.5 and 10 Hz: 1H); 5.23 (dd, J=7.5 and 4.5 Hz: 1H); from 6.20 to 7.00 (broad multiplet: 2H); from 7.35 to 7.60 (mt: 3H); from 7.50 to 8.20 (broad multiplet: 2H).

後処理

  1. customN-[(7-Fluoro-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetyl]guanidine is prepared
  2. filtrationis then filtered
  3. customAfter separation of the phases
  4. customthe organic phase is separated out
  5. extractionthe aqueous phase is extracted with twice 60 cm3 of ethyl acetate
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (0.6 kPa) at a temperature in the region of 55° C
  9. concentrationconcentrated to dryness again under the same conditions
  10. concentrationconcentrated to dryness again under the same conditions
  11. customThe residue is purified by chromatography under argon pressure (50 kPa)
  12. washon a column of silica gel (particle size 15-40 μm), eluting with a mixture of dichloromethane/methanol (90/10 by volume)
  13. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 20° C
  14. customtriturated
  15. filtrationfiltered
  16. customdried

出典と根拠

ORDレコード
ord-b26b8cc95c394012a60e4abbe9089f3f
出典データセット
uspto-grants-2009_09
特許番号
US07589117B2

反応ノート

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