1,2-Dichloroethane → Ammonium Hydroxide

HRID 1890718Notes

Reaction equation

HRID 1890718 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]([NH:19][CH2:20][C:21]2[CH:22]=[N:23][C:24]3[C:29]([CH:30]=2)=[CH:28][C:27]2[CH2:31][C@:32]4([CH2:42][C:26]=2[CH:25]=3)[C:40]2[C:35](=[N:36][CH:37]=[CH:38][CH:39]=2)[NH:34][C:33]4=[O:41])([CH3:18])[CH2:10][NH:11][C:12]([CH3:17])([C:14](O)=[O:15])[CH3:13])[CH:5]=[C:6]([F:8])[CH:7]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C.C([O-])(O)=O.[Na+]>[NH4+:11].[OH-:15].[F:1][C:2]1[CH:3]=[C:4]([C@:9]2([CH3:18])[CH2:10][NH:11][C:12]([CH3:17])([CH3:13])[C:14](=[O:15])[N:19]2[CH2:20][C:21]2[CH:22]=[N:23][C:24]3[C:29]([CH:30]=2)=[CH:28][C:27]2[CH2:31][C@:32]4([CH2:42][C:26]=2[CH:25]=3)[C:40]2[C:35](=[N:36][CH:37]=[CH:38][CH:39]=2)[NH:34][C:33]4=[O:41])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 58550628HCID 58550628, compound

Product 2

HCID 14923Ammonium HydroxideHCID 58550636HCID 58550636, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of N-[2-(3,5-difluorophenyl)-2-({[(7S)-2′-oxo-1′,2′,6,8-tetrahydrospiro[cyclopenta[g]quinoline-7,3′-pyrrolo[2,3-b]pyridin]-3-yl]methyl}amino)propyl]-2-methylalanine from Step D (150 mg, 0.262 mmol), EDC (60.4 mg, 0.315 mmol), HOBT (48.2 mg, 0.315 mmol), and DIEA (0.229 mL, 1.31 mmol) in DMF (5 mL) was stirred for 16 h. The reaction mixture was diluted with saturated aqueous NaHCO3 (20 mL) and extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4OH—100:0:0 to 90:10:1, to give the title compound as a mixture of diastereomers. The mixture of diastereomers were resolved by HPLC, utilizing a Chiralpak AS-H column and eluting with MeOH:CO2—20:80. The first major peak to elute was (7S)-3-{[(2R)-2-(3,5-Difluorophenyl)-2,5,5-trimethyl-6-oxopiperazin-1-yl]methyl}-6,8-dihydrospiro[cyclopenta[g]quinoline-7,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one, isomer A, and the second major peak to elute was (7S)-{[(2R)-2-(3,5-Difluorophenyl)-2,5,5-trimethyl-6-oxopiperazin-1-yl]methyl}-6,8-dihydrospiro[cyclopenta[g]quinoline-7,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one, isomer B, the title compound. MS: m/z=554 (M+1). HRMS: m/z=554.2365; calculated m/z=554.2362 for C32H30F2N5O2.

Workup

  1. extractionextracted with CH2Cl2 (3×10 mL)
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by silica gel chromatography
  6. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-0bf0ee0486ce4c528ba8a4eadb209bc2
Source dataset
uspto-grants-2013_08
Patent number
US08507477B2

Reaction notes

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