Phosgene → HCID 89714647, compound

HRID 2273083Notes

Reaction equation

HRID 2273083 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[CH2:30][CH:29]4[O:31][CH:26]([CH2:27][CH2:28]4)[CH2:25]3)[N:9]=2)=[CH:4][C:3]=1[F:32].[C:33](Cl)(Cl)=[O:34].CCN(C(C)C)C(C)C.[OH:46][C:47]([CH3:51])([CH3:50])[CH2:48][NH2:49]>O1CCOCC1.C1(C)C=CC=CC=1.O.C(Cl)Cl>[CH2:20]([N:16]1[CH2:15][C:14]([CH3:22])([CH3:23])[O:13][C:12]2[N:11]=[C:10]([N:24]3[CH2:25][CH:26]4[O:31][CH:29]([CH2:28][CH2:27]4)[CH2:30]3)[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:33]([NH:49][CH2:48][C:47]([OH:46])([CH3:51])[CH3:50])=[O:34])=[C:3]([F:32])[CH:4]=3)[C:18]=2[C:17]1=[O:19])[CH3:21]

Participants

9

Reactant 4

HCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 951022-Propanol, 1-amino-2-methyl-HCID 89714851HCID 89714851, compound

Product 1

HCID 89714647HCID 89714647, compoundYield 52.3%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

100 mg (226.5 μmol) of 4-(4-amino-3-fluorophenyl)-6-ethyl-8,8-dimethyl-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-7,8-dihydro-6H-9-oxa-1,3,6-triazabenzocyclohepten-5-one suspended in 2 ml of dioxane are heated at 50° C. for 30 minutes in the presence of 179 μl of a 1.9 M solution of phosgene (339.75 μmol) in toluene and 58 μl (339.5 μmol) of DIEA. 101 mg (1.13 mmol) of 2-hydroxy-2-methylpropylamine dissolved in 1 ml of dioxane are then added. The reaction medium is stirred for 16 hours at room temperature and then diluted with water. The precipitate formed is filtered off and washed with water and then with ether. The solid obtained is dissolved in a minimum amount of DCM and then reprecipitated from ether to give 66 mg of 1-{4-[6-ethyl-8,8-dimethyl-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-5-oxo-5,6,7,8-tetrahydro-9-oxa-1,3,6-triazabenzocyclohepten-4-yl]-2-fluorophenyl}-3-(2-hydroxy-2-methylpropyl)urea.

Workup

  1. additionare then added
  2. customThe precipitate formed
  3. filtrationis filtered off
  4. washwashed with water
  5. customThe solid obtained
  6. customreprecipitated from ether

Sources & evidence

ORD record
ord-f46c8e3659ab4c01ac6b617514bf8d0e
Source dataset
uspto-grants-2015_09
Patent number
US09120812B2

Reaction notes

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