Pivaloyl chloride → HCID 178502457, compound

HRID 1504342Notes

Reaction equation

HRID 1504342 reaction equation
Cl.Cl.Cl.[CH3:4][O:5][C:6](=[O:60])[NH:7][C@H:8]([C:12]([N:14]1[CH2:18][C@@H:17]([O:19][CH3:20])[CH2:16][C@H:15]1[C:21]1[NH:22][CH:23]=[C:24]([C:26]2[CH:31]=[CH:30][C:29]([C:32]3[CH:37]=[C:36]([Cl:38])[C:35]([NH:39][C:40]([C:42]4[CH:43]=[N:44][C:45]([N:48]5[CH2:53][CH2:52][NH:51][CH2:50][C@H:49]5[CH3:54])=[CH:46][CH:47]=4)=[O:41])=[CH:34][C:33]=3[O:55][C:56]([F:59])([F:58])[F:57])=[CH:28][CH:27]=2)[N:25]=1)=[O:13])[CH:9]([CH3:11])[CH3:10].C(N(CC)C(C)C)(C)C.[CH3:70][C:71](C)([CH3:75])[C:72](Cl)=O>CC(N(C)C)=O>[CH3:4][O:5][C:6](=[O:60])[NH:7][C@H:8]([C:12]([N:14]1[CH2:18][C@@H:17]([O:19][CH3:20])[CH2:16][C@H:15]1[C:21]1[NH:22][CH:23]=[C:24]([C:26]2[CH:31]=[CH:30][C:29]([C:32]3[CH:37]=[C:36]([Cl:38])[C:35]([NH:39][C:40]([C:42]4[CH:43]=[N:44][C:45]([N:48]5[CH2:53][CH2:52][N:51]([C:71]([CH3:75])([CH3:72])[CH3:70])[CH2:50][C@H:49]5[CH3:54])=[CH:46][CH:47]=4)=[O:41])=[CH:34][C:33]=3[O:55][C:56]([F:59])([F:58])[F:57])=[CH:28][CH:27]=2)[N:25]=1)=[O:13])[CH:9]([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 178502458HCID 178502458, compound

Product 1

HCID 178502457HCID 178502457, compoundYield 80.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of ((S)-1-{(2S,4S)-2-[4-(5′-chloro-4′-{[6-((R)-2-methyl-piperazin-1-yl)-pyridine-3-carbonyl]-amino}-2′-trifluoromethoxy-biphenyl-4-yl)-1H-imidazol-2-yl]-4-methoxy-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester tri-HCl (10 mg, 0.01 mmol; Preparation 28) in DMA (1 mL) was added N,N-diisopropylethylamine (9.44 μL, 0.05 mmol) followed by 2,2-dimethylpropanoyl chloride (1.31 mg, 0.01 mmol). The reaction mixture was stirred at RT overnight, concentrated by rotary evaporation, dissolved in 1:1 acetic acid:water (1.5 mL) and purified by reverse phase HPLC to provide the di-TFA salt of the title compound (7 mg, 51% yield) (m/z): [M+H]+ calcd for C44H52ClF3N8O7 897.36. found 897.8.

Workup

  1. concentrationconcentrated by rotary evaporation
  2. dissolutiondissolved in 1:1 acetic acid
  3. customwater (1.5 mL) and purified by reverse phase HPLC

Sources & evidence

ORD record
ord-8aba4e126e5e4287817227c985a2865f
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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