Triethylamine → Ammonium Hydroxide

HRID 1367253Notes

Reaction equation

HRID 1367253 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:25](=[CH:26][CH:27]=1)[CH2:24][C@:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[N:8](C[O:16]CC[Si](C)(C)C)[C:7]1=[O:23])[CH2:5]2.C(N(CC)CC)C.Br[CH2:36][C:37](Br)=[O:38].Cl.Cl.[NH2:42][C@H:43]([C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[CH2:44][CH2:45][NH:46][C:47]1([C:52]([O:54][CH3:55])=[O:53])[CH2:51][CH2:50][CH2:49][CH2:48]1>C1COCC1.C(Cl)(Cl)Cl.C(=O)(O)[O-].[Na+]>[NH4+:1].[OH-:16].[O:38]=[C:37]([NH:1][C:2]1[CH:3]=[C:4]2[C:25](=[CH:26][CH:27]=1)[CH2:24][C@:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]1=[O:23])[CH2:5]2)[CH2:36][NH:42][C@H:43]([C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1)[CH2:44][CH2:45][NH:46][C:47]1([C:52]([O:54][CH3:55])=[O:53])[CH2:51][CH2:50][CH2:49][CH2:48]1

Participants

9

Reactant 4

HCID 8471Triethylamine2×HCID 61147Bromoacetyl bromideHCID 66973378Methyl 1-{[(3S)-3-amino-3-phenylpropyl]amino}cyclopentanecarboxylate bis-hydrochloride2×HCID 66973634(R)-5-amino-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2×

Product 2

HCID 14923Ammonium HydroxideHCID 66973034Methyl 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

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a cooled (0° C.) solution of (2R)-5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (0.100 g, 0.398 mmol, Intermediate 9) and triethylamine (100. μL, 0.716 mmol) in THF (8 mL) was added bromoacetyl bromide (46.0 μL, 0.523 mmol). After allowing the reaction to warm to ambient temperature, triethylamine (0.230 mL, 1.67 mmol) and methyl 1-{[(3S)-3-amino-3-phenylpropyl]amino}cyclopentanecarboxylate bis-hydrochloride (0.139 g, 0.398 mmol, Intermediate 38) were added, prior to heating the reaction to 50° C. for 17 h. After cooling to ambient temperature, the reaction mixture was diluted with chloroform and saturated aqueous sodium bicarbonate. The aqueous layer was extracted twice with additional chloroform. 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:NH4OH—99:1:0.1 to 92:8:0.8, to give the title compound. MS: m/z=568 (M+1).

Workup

  1. customthe reaction
  2. temperatureto heating
  3. customthe reaction to 50° C. for 17 h
  4. temperatureAfter cooling to ambient temperature
  5. extractionThe aqueous layer was extracted twice with additional chloroform
  6. dry with materialThe combined organics were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give an oil
  10. customThis oil was purified by silica gel chromatography
  11. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-599137b9da784a11982cfbb9bf934ad0
Source dataset
uspto-grants-2011_02
Patent number
US07893079B2

Reaction notes

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