Sodium Hydroxide → HCID 11953000, compound

HRID 1241466Notes

Reaction equation

HRID 1241466 reaction equation
C([O:5][C:6]([CH2:8][CH2:9][CH2:10][CH2:11][N:12]1[C:18]2[CH:19]=[CH:20][C:21]([C:23]([OH:25])=O)=[CH:22][C:17]=2[C:16](=[O:26])[N:15]([C@@H:27]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)[CH3:28])[C@@H:14]([C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=2)[C:13]1=[O:43])=[O:7])(C)(C)C.F[P-](F)(F)(F)(F)F.[N:51]1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C1C=CC2N(O)N=NC=2C=1.[Cl-].[NH4+].[Na].[OH-].[Na+]>CN(C=O)C.ClCCl.C(O)(C(F)(F)F)=O.CCO>[NH2:51][C:23]([C:21]1[CH:20]=[CH:19][C:18]2[N:12]([CH2:11][CH2:10][CH2:9][CH2:8][C:6]([OH:5])=[O:7])[C:13](=[O:43])[C@H:14]([C:36]3[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=3)[N:15]([C@@H:27]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=3)[CH3:28])[C:16](=[O:26])[C:17]=2[CH:22]=1)=[O:25]

Participants

11

Reactant 6

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 5360545SodiumHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11952999HCID 11952999, compound

Product 1

HCID 11953000HCID 11953000, compoundYield 65.1%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (3S)-1-(4-tert-Butoxycarbonyl-butyl)-3-(4-chloro-phenyl)-4-[(R)-1-(4-chloro-phenyl)-ethyl]-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]-diazepine-7-carboxylic acid (Example 33) (63 mg, 0.10 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (57 mg, 0.15 mmol), HOBT (20 mg, 0.15 mmol) N,N-diisopropylethylamine (70 μL, 0.4 mmol), ammonium chloride (11 mg, 0.2 mmol) in DMF (400 μL) was stirred at room temperature for 1 h. under argon atmosphere. After evaporation of the solvent, the residue was diluted with EtOAc (15 mL), washed with water (10 mL), dried (Na2SO4) then concentrated to dryness under reduced pressure. Chromatography on silica (EtOAc/hexanes, 1:1) afforded anoil (58 mg), which was dissolved in dichloromethane (1.5 mL) and TFA (0.5 mL). This solution was stirred at room temperature for 10 h, then evaporated to dryness. The residue was dissolved in ice-cold water (10 mL) and AcONa (100 mg)/AcOH (100 μL) were added. The solution was extracted with ether (3×20 mL), then the organic layer was dried (Na2SO4) and concentrated to dryness under reduced pressure. Purification by column chromatography (EtOAc/CH2Cl2/EtOH, 5:4:1) afforded a colorless oil, which was converted to its sodium salt with NaOH 1N in EtOH. Recrystallization from EtOH/ether yielded title compound (37 mg, 62%) as a white powder: Mass spectrum (LCMS, ESI pos.): Calcd for C29H27Cl2IN3O5: 567.13; found 568.0 (M+H).

Workup

  1. customAfter evaporation of the solvent
  2. additionthe residue was diluted with EtOAc (15 mL)
  3. washwashed with water (10 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationthen concentrated to dryness under reduced pressure
  6. customChromatography on silica (EtOAc/hexanes, 1:1) afforded anoil (58 mg), which
  7. customevaporated to dryness
  8. dissolutionThe residue was dissolved in ice-cold water (10 mL)
  9. additionAcONa (100 mg)/AcOH (100 μL) were added
  10. extractionThe solution was extracted with ether (3×20 mL)
  11. dry with materialthe organic layer was dried (Na2SO4)
  12. concentrationconcentrated to dryness under reduced pressure
  13. customPurification by column chromatography (EtOAc/CH2Cl2/EtOH, 5:4:1)
  14. customafforded a colorless oil, which
  15. customRecrystallization from EtOH/ether

Sources & evidence

ORD record
ord-ab995bc26f414855835c6a79669b910e
Source dataset
uspto-grants-2006_10
Patent number
US07115598B2

Reaction notes

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