Toluene → HCID 45256715, compound

HRID 906444Notes

Reaction equation

HRID 906444 reaction equation
[Si]([O:8][CH2:9][C:10]([CH3:55])([CH3:54])[CH2:11][N:12]1[CH:21]=[C:20]([S:22]([N:25]2[CH2:31][CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]2)(=[O:24])=[O:23])[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:39]3[CH:44]=[C:43]([C:45](=[O:50])[NH:46][CH:47]4[CH2:49][CH2:48]4)[CH:42]=[C:41]([F:51])[C:40]=3[CH3:52])[CH:18]=2)[C:13]1=[O:53])(C(C)(C)C)(C)C.FC(F)(F)C(O)=O.C1(C)C=CC=CC=1>C(Cl)Cl>[CH:47]1([NH:46][C:45](=[O:50])[C:43]2[CH:42]=[C:41]([F:51])[C:40]([CH3:52])=[C:39]([C:17]3[CH:18]=[C:19]4[C:14](=[CH:15][CH:16]=3)[C:13](=[O:53])[N:12]([CH2:11][C:10]([CH3:55])([CH3:54])[CH2:9][OH:8])[CH:21]=[C:20]4[S:22]([N:25]3[CH2:31][CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)(=[O:24])=[O:23])[CH:44]=2)[CH2:49][CH2:48]1

Participants

5

Reactant 3

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 67391407HCID 67391407, compound

Product 1

HCID 45256715HCID 45256715, compoundYield 27.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-({2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl}sulfonyl)-1,4-diazepane-1-carboxylate (Example 46d, 0.055 g) in DCM (4 mL) was added trifluoroacetic acid (1 mL), and the reaction was stirred at room temperature overnight. Toluene (6 mL) was added and the volatiles removed in vacuo (repeated 3 times). The residue was dissolved in methanol and purified by SCX, flushing with methanol (impurities), and eluting the product with 0.7 N methanolic ammonia. Purification by preparative HPLC (Phenomenex Gemini column using a 95-5% gradient of 0.2% aqueous trifluoroacetic acid in acetonitrile as eluent), evaporation of solvents and trituration with diethyl ether gave the title compound (0.011 g) as a white solid.

Workup

  1. customthe volatiles removed in vacuo (repeated 3 times)
  2. dissolutionThe residue was dissolved in methanol
  3. custompurified by SCX
  4. customflushing with methanol (impurities)
  5. washeluting the product with 0.7 N methanolic ammonia
  6. customPurification by preparative HPLC (Phenomenex Gemini column
  7. customevaporation of solvents and trituration with diethyl ether

Sources & evidence

ORD record
ord-e4109b8ad8f3497ab16304c8799c5a90
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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