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 1864934Notes

Reaction equation

HRID 1864934 reaction equation
[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]

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
40 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-71a4dbdc5fff43f3988dbc6489015b85
Source dataset
uspto-grants-2009_12
Patent number
US07625901B2

Reaction notes

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