Ammonia → HCID 67998960, compound

HRID 932117Notes

Reaction equation

HRID 932117 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:31][CH3:32])[CH2:22][N:23]([CH3:30])[S:24]([CH:27]3[CH2:29][CH2:28]3)(=[O:26])=[O:25])[C:11](=[O:33])[C@:10]([CH2:35][C:36](O)=[O:37])([CH3:34])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C[N:40](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+].N.CO>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([C@@H:21]([CH2:31][CH3:32])[CH2:22][N:23]([CH3:30])[S:24]([CH:27]3[CH2:29][CH2:28]3)(=[O:25])=[O:26])[C:11](=[O:33])[C@:10]([CH2:35][C:36]([NH2:40])=[O:37])([CH3:34])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 6

HCID 222AmmoniaHCID 887MethanolHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67999393HCID 67999393, compound

Product 1

HCID 67998960HCID 67998960, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-1-(N-methylcyclopropanesulfonamido)butan-2-yl)-2-oxopiperidin-3-yl)acetic acid (0.055 g, 0.095 mmol; Example 141) in DMF (2.0 mL) was treated with HBTU (0.072 g, 0.189 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.036 g, 0.189 mmol) and sodium hydrogencarbonate (0.016 g, 0.189 mmol) successively. Let it stir for 0.5 h. 7.0M ammonia in methanol (0.135 mL, 0.946 mmol) was added dropwise. After being stirred at room temperature for 18 h, the reaction was diluted with water, extracted (2×EtOAc), and washed (1×saturated NaHCO3, and 2×sat. aq. NaCl solution). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by reverse phase preparatory HPLC (eluent: 10 to 90% acetonitrile, water, 0.1% TFA, gradient elution) to give the title compound as a white solid after lyophilization.

Workup

  1. stirringAfter being stirred at room temperature for 18 h
  2. extractionextracted (2×EtOAc)
  3. washwashed (1×saturated NaHCO3, and 2×sat. aq. NaCl solution)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by reverse phase preparatory HPLC (eluent: 10 to 90% acetonitrile, water, 0.1% TFA, gradient elution)

Sources & evidence

ORD record
ord-124c08338f6e4c10975d53e3dcaa9bab
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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