Toluene → HCID 89714767, compound

HRID 2273082Notes

Reaction equation

HRID 2273082 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:18]3[C:17](=[O:19])[N:16]([CH2:20][CH3:21])[CH2:15][C:14]([CH3:23])([CH3:22])[O:13][C:12]=3[N:11]=[C:10]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][C@@H:25]3[CH3:30])[N:9]=2)=[CH:4][CH:3]=1.[C:31](Cl)(Cl)=[O:32].C1(C)C=CC=CC=1.CCN(C(C)C)C(C)C.[NH2:51][C:52]1[CH:57]=[CH:56][C:55]([C:58]([N:60]2[CH2:65][CH2:64][CH:63]([N:66]([CH3:68])[CH3:67])[CH2:62][CH2:61]2)=[O:59])=[CH:54][CH:53]=1>O1CCOCC1.C(Cl)Cl>[CH3:67][N:66]([CH3:68])[CH:63]1[CH2:62][CH2:61][N:60]([C:58]([C:55]2[CH:54]=[CH:53][C:52]([NH:51][C:31]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([C:8]4[C:18]5[C:17](=[O:19])[N:16]([CH2:20][CH3:21])[CH2:15][C:14]([CH3:23])([CH3:22])[O:13][C:12]=5[N:11]=[C:10]([N:24]5[CH2:29][CH2:28][O:27][CH2:26][C@@H:25]5[CH3:30])[N:9]=4)=[CH:6][CH:7]=3)=[O:32])=[CH:57][CH:56]=2)=[O:59])[CH2:65][CH2:64]1

Participants

8

Reactant 5

HCID 1140TolueneHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 22567534(4-aminophenyl)[4-(dimethylamino)-1-piperidinyl]methanoneHCID 89714935HCID 89714935, compound

Product 1

HCID 89714767HCID 89714767, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

130 mg (316 μmol) of 4-(4-aminophenyl)-6-ethyl-8,8-dimethyl-2-((S)-3-methylmorpholin-4-yl)-7,8-dihydro-6H-9-oxa-1,3,6-triazabenzocyclohepten-5-one suspended in 3 ml of dioxane are heated at 50° C. for 30 minutes in the presence of 233 μl of a 1.9 M solution of phosgene in toluene (442.3 mmol) and 75 μl (442.3 mmol) of DIEA. 391 mg (1.58 mmol) of (4-aminophenyl)-(4-dimethylaminopiperidin-1-yl)methanone are then added. The medium is stirred for 16 hours at room temperature. The mixture is evaporated under reduced pressure and the residue is taken up in water and extracted with DCM. The organic phase is washed twice with water, dried over MgSO4 and then filtered. The filtrate is evaporated under reduced pressure and the residue is then chromatographed on silica gel, eluting with a DCM/MeOH mixture from (100/0 v/v) up to (93/7 v/v). The product obtained is dissolved in a minimum amount of DCM and then reprecipitated from Et2O to give 61 mg of 1-[4-(4-dimethylaminopiperidine-1-carbonyl)phenyl]-3-{4-[6-ethyl-8,8-dimethyl-2-((S)-3-methylmorpholin-4-yl)-5-oxo-5,6,7,8-tetrahydro-9-oxa-1,3,6-triazabenzocyclohepten-4-yl]phenyl}urea.

Workup

  1. customThe mixture is evaporated under reduced pressure
  2. extractionextracted with DCM
  3. washThe organic phase is washed twice with water
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customThe filtrate is evaporated under reduced pressure
  7. customthe residue is then chromatographed on silica gel
  8. washeluting with a DCM/MeOH mixture from (100/0 v/v) up to (93/7 v/v)
  9. customThe product obtained
  10. customreprecipitated from Et2O

Sources & evidence

ORD record
ord-e207753e92034df791cc6141c2195a4f
Source dataset
uspto-grants-2015_09
Patent number
US09120812B2

Reaction notes

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