Hydrochloric Acid → HCID 178432513、化合物

HRID 1621963ノート

反応式

HRID 1621963 の反応式
[Cl:1][C:2]1[C:7]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[CH:6][C:5]([NH:13][C:14]2[C:19]([C:20]3[N:28]=[C:27]([CH3:29])[N:26]=[C:25]4[C:21]=3[N:22]=[CH:23][N:24]4C3CCCCO3)=[CH:18][C:17]([CH:36]([N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[CH3:37])=[CH:16][N:15]=2)=[CH:4][N:3]=1.Cl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[OH-].[Na+]>[OH-].[Na+].C1COCC1>[Cl:1][C:2]1[C:7]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[CH:6][C:5]([NH:13][C:14]2[C:19]([C:20]3[N:28]=[C:27]([CH3:29])[N:26]=[C:25]4[C:21]=3[N:22]=[CH:23][NH:24]4)=[CH:18][C:17]([CH:36]([N:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)[CH3:37])=[CH:16][N:15]=2)=[CH:4][N:3]=1

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 23674961citric acid NaOHHCID 86647079N-(2-chloro-5-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-(1-morpholinoethyl)pyridin-2-ylamino)pyridin-3-yl)methanesulfonamide

生成物 1

HCID 178432513HCID 178432513、化合物収率 70.6%

試薬・触媒・溶媒 2

HCID 14798Sodium Hydroxide触媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a 20 mL scintillation vial, N-(2-chloro-5-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-(1-morpholinoethyl)pyridin-2-ylamino)pyridin-3-yl)methanesulfonamide (0.165 g, 0.263 mmol) and 5N hydrochloric acid (0.5 mL, 2.5 mmol) were mixed into THF (3 mL). The solution was stirred at room temperature for 30 min. 10 mL of buffer (pH 5, citric acid/NaOH) was added and the pH was further adjusted to about 5 by adding a few drops of 6N NaOH. The aqueous phase was extracted with 10% isopropanol in chloroform (3×20 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by preparative HPLC using a Phenomenex, Gemni 5 micron C18 100×30 mm column (1% to 90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min). The corresponding fractions were collected and concentrated down to dryness. The residue was treated with about 5 mL of pH 5 buffer and pH 7 buffer were added to adjust pH to about 6. The aqueous phase was extracted with 10% isopropanol in chloroform (3×20 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo to afford 0.101 g of yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.65 (br. s., 1H) 13.11 (br. s., 1H) 9.82 (br. s., 1H) 9.68 (br. s., 1H) 8.71 (d, J=1.96 Hz, 1H) 8.66 (s, 1H) 8.53 (s, 1H) 8.34 (d, J=1.17 Hz, 1H) 3.50-3.67 (m, 5H) 3.15 (s, 3H) 2.88 (s, 3H) 2.35-2.46 (m, 2H) 1.42 (d, J=6.65 Hz, 3H). Note: 2 protons were buried under DMSO peak and could not be integrated. m/z (ESI, positive ion): 544.0 (M+H)+.

後処理

  1. extractionThe aqueous phase was extracted with 10% isopropanol in chloroform (3×20 mL)
  2. dry with materialThe combined organic phases were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by preparative HPLC
  6. customC18 100×30 mm column (1% to 90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min)
  7. customThe corresponding fractions were collected
  8. concentrationconcentrated down to dryness
  9. additionThe residue was treated with about 5 mL of pH 5 buffer
  10. additionpH 7 buffer were added
  11. extractionThe aqueous phase was extracted with 10% isopropanol in chloroform (3×20 mL)
  12. dry with materialThe combined organic phases were dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-31257e9e1cd845dda1a2f7ff4539d020
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

反応ノート

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