1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-[(9S)-11-Oxo-9-phenyl-6,10-diazaspiro[4.6]undec-10-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

HRID 1367255Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1367255
[O:1]=[C:2]([NH:23][C:24]1[CH:25]=[C:26]2[C:39](=[CH:40][CH:41]=1)[CH2:38][C@:28]1([C:36]3[C:31](=[N:32][CH:33]=[CH:34][CH:35]=3)[NH:30][C:29]1=[O:37])[CH2:27]2)[CH2:3][NH:4][C@H:5]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:6][CH2:7][NH:8][C:9]1([C:14]([O-])=[O:15])[CH2:13][CH2:12][CH2:11][CH2:10]1.[K+].CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.C(=O)(O)[O-].[Na+].C(Cl)(Cl)Cl>[O:15]=[C:14]1[C:9]2([CH2:10][CH2:11][CH2:12][CH2:13]2)[NH:8][CH2:7][CH2:6][C@@H:5]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:4]1[CH2:3][C:2]([NH:23][C:24]1[CH:25]=[C:26]2[C:39](=[CH:40][CH:41]=1)[CH2:38][C@:28]1([C:36]3[C:31](=[N:32][CH:33]=[CH:34][CH:35]=3)[NH:30][C:29]1=[O:37])[CH2:27]2)=[O:1]

Komponenten

7

Edukt 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide2×HCID 181649HOAtHCID 66973455Potassium 1-({(3S)-3-[(2-oxo-2-{[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]amino}ethyl)amino]-3-phenylpropyl}amino)cyclo-pentanecarboxylate

Produkt 1

HCID 250199952-[(9S)-11-Oxo-9-phenyl-6,10-diazaspiro[4.6]undec-10-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6212ChloroformLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a stirred solution of potassium 1-({(3S)-3-[(2-oxo-2-{[(2R)-2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-5-yl]amino}ethyl)amino]-3-phenylpropyl}amino)cyclopentanecarboxylate from Step B (0.147 g, 0.249 mmol) in DMF (8.3 mL) was added EDCI (0.0720 g, 0.374 mmol) and HOAt (0.0340 g, 0.249 mmol). The reaction mixture was then heated to 40° C. After 1 h, additional EDCI (0.0350 mg) was added and the reaction temperature was increased to 50° C., for 15 h. The reaction was allowed to cool to ambient temperature before being diluted with 5% aqueous sodium bicarbonate (100 mL) and chloroform (100 mL). The organics were washed successively with water (100 mL) and saturated brine (100 mL). The combined organics were dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH—99:1 to 91:9, to give the title compound. MS: m/z=536 (M+1). HRMS: m/z=536.2694; calculated m/z=536.2656 for C32H34N5O3.

Aufarbeitung

  1. temperaturethe reaction temperature was increased to 50° C., for 15 h
  2. temperatureto cool to ambient temperature
  3. washThe organics were washed successively with water (100 mL) and saturated brine (100 mL)
  4. dry with materialThe combined organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil
  8. customThis oil was purified by silica gel chromatography
  9. washeluting with a gradient of CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-b549b58e15e145cfaf488ebdc547db72
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07893079B2

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