HCID 178502328, compound → HCID 178502322, compound

HRID 1751609Notes

Reaction equation

HRID 1751609 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[CH:13]=[C:14]4[C:38](=[CH:39][CH:40]=3)[C:18]3[NH:19][C:20]([C@@H:22]5[CH2:26][CH2:25][CH2:24][N:23]5[C:27](=[O:37])[C@@H:28]([NH:32][C:33]([O:35][CH3:36])=[O:34])[CH:29]([CH3:31])[CH3:30])=[N:21][C:17]=3[CH:16]=[CH:15]4)=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[NH:41][C:42]([C@@H:44]1[CH2:48][C@H:47]([S:49][CH3:50])[CH2:46][N:45]1[C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=O>C(O)(=O)C>[CH3:36][O:35][C:33]([NH:32][C@H:28]([C:27]([N:23]1[CH2:24][CH2:25][CH2:26][C@H:22]1[C:20]1[NH:19][C:18]2[C:38]3[C:14]([CH:15]=[CH:16][C:17]=2[N:21]=1)=[CH:13][C:12]([C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[C:2]1[NH:1][C:42]([C@@H:44]4[CH2:48][C@H:47]([S:49][CH3:50])[CH2:46][N:45]4[C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=[N:41][C:3]=1[CH:4]=[CH:5]2)=[CH:40][CH:39]=3)=[O:37])[CH:29]([CH3:30])[CH3:31])=[O:34]

Participants

3

Reactant 1

HCID 178502328HCID 178502328, compound

Product 1

HCID 178502322HCID 178502322, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To (2S,4S)-tert-butyl 2-(1-amino-6-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-naphtho[1,2-d]imidazol-7-yl) naphthalen-2-ylcarbamoyl)-4-(methylthio)pyrrolidine-1-carboxylate (95 mg, 0.12 mmol) in acetic acid (4 mL) and the reaction mixture stirred for 16 hours. Concentrated in vacuo and diluted with EtOAc, washed with sat. NaHCO3 aqueous (2×) and sat. NaCl aqueous (1×). The organic layer was concentrated down after drying over sodium sulfate and subject to silica gel chromatography with an eluent of ethyl acetate and hexane at a gradient of 40-100% with an ISCO column (12 g silica gel). The fractions containing product were combined and the solvent was removed under reduced pressure to provide tert-butyl (2S,4S)-2-(2′-{(2S)-1-[N-(methoxycarbonyl)-L-valyl]pyrrolidin-2-yl}-1H,1′H-7,7′-binaphtho[1,2-d]imidazol-2-yl)-4-(methylsulfanyl)pyrrolidine-1-carboxylate (50 mg, 54%). MS (ESI) m/z 777 [M+H]+.

Workup

  1. concentrationConcentrated in vacuo
  2. additiondiluted with EtOAc
  3. washwashed with sat. NaHCO3 aqueous (2×) and sat. NaCl aqueous (1×)
  4. concentrationThe organic layer was concentrated down
  5. dry with materialafter drying over sodium sulfate
  6. additionThe fractions containing product
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-423e4ab7f63a485daf5f0c8d9fa6e82a
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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