Ammonia → HCID 67998631, compound

HRID 932071Notes

Reaction equation

HRID 932071 reaction equation
[C:1]([O:5][C:6](=[O:36])[C@@H:7]([N:10]1[C@H:15]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)[C@@H:14]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[CH2:13][C@@:12]([CH2:31][C:32](O)=[O:33])([CH3:30])[C:11]1=[O:35])[CH2:8][CH3:9])([CH3:4])([CH3:3])[CH3:2].Cl.C[N:39](C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C([O-])(O)=O.[Na+].N.CO>CN(C=O)C.O>[NH2:39][C:32](=[O:33])[CH2:31][C@@:12]1([CH3:30])[CH2:13][C@H:14]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[C@@H:15]([C:16]2[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=2)[N:10]([C@@H:7]([CH2:8][CH3:9])[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:36])[C:11]1=[O:35]

Participants

9

Reactant 6

HCID 222AmmoniaHCID 887MethanolHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 56591154HCID 56591154, compound

Product 1

HCID 67998631HCID 67998631, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-((3R,5R,6S)-1-((S)-1-tert-butoxy-1-oxobutan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid (230 mg, 0.430 mmol; Example 67) in DMF (4.3 mL) was treated with N-(3-dimethyaminopropyl)-N′-ethylcarbodiimide hydrochloride (165 mg, 0.86 mmol), 1-hydroxy-7-azabenzotriazole (117 mg, 0.86 mmol) and NaHCO3 (72.3 mg, 0.861 mmol) successively. After being stirred at rt for 0.5 h, 7 M ammonia in methanol (6.2 mL, 4.30 mmol) was added dropwise and the reaction was stirred overnight. Then, the reaction was diluted (water), extracted (2×EtOAc), and washed (1× saturated NaHCO3, and 2×sat. aq. NaCl solution). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification by RP-HPLC (45 to 70% MeCN/H2O (0.1% TFA), a gradient elution) provided the title compound as a white solid.

Workup

  1. stirringthe reaction was stirred overnight
  2. extractionextracted (2×EtOAc)
  3. washwashed (1× saturated NaHCO3, and 2×sat. aq. NaCl solution)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customPurification by RP-HPLC (45 to 70% MeCN/H2O (0.1% TFA)
  7. washa gradient elution)

Sources & evidence

ORD record
ord-f729dd5b6bce4e1eb2d57e19ad309f30
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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