Phenyl chloroformate → HCID 89714526, compound

HRID 2273077Notes

Reaction equation

HRID 2273077 reaction equation
[F:1][CH:2]([F:11])[O:3][C:4]1[CH:5]=[C:6]([NH2:10])[CH:7]=[CH:8][CH:9]=1.CCN(C(C)C)C(C)C.Cl[C:22](OC1C=CC=CC=1)=[O:23].[NH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[C:48]3[C:47](=[O:49])[N:46]([CH2:50][CH3:51])[CH2:45][C:44]([CH3:53])([CH3:52])[O:43][C:42]=3[N:41]=[C:40]([N:54]3[CH2:60][CH:59]4[O:61][CH:56]([CH2:57][CH2:58]4)[CH2:55]3)[N:39]=2)=[CH:34][CH:33]=1>C1COCC1>[F:1][CH:2]([F:11])[O:3][C:4]1[CH:5]=[C:6]([NH:10][C:22]([NH:31][C:32]2[CH:33]=[CH:34][C:35]([C:38]3[C:48]4[C:47](=[O:49])[N:46]([CH2:50][CH3:51])[CH2:45][C:44]([CH3:53])([CH3:52])[O:43][C:42]=4[N:41]=[C:40]([N:54]4[CH2:55][CH:56]5[O:61][CH:59]([CH2:58][CH2:57]5)[CH2:60]4)[N:39]=3)=[CH:36][CH:37]=2)=[O:23])[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 15891Phenyl chloroformateHCID 81531DiisopropylethylamineHCID 27741103-(Difluoromethoxy)anilineHCID 89714581HCID 89714581, compound

Product 1

HCID 89714526HCID 89714526, compoundYield 124.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

96.84 mg of 3-difluoromethoxyphenylamine (590.31 μmol), 206.20 μl of DIEA (1.18 mmol) and 30.81 μl of phenyl choroformate (237.83 μmol) are added to 4 ml of THF in a microwave tube. The mixture is stirred at room temperature for 20 minutes. 250 mg of 4-(4-aminophenyl)-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 (590.31 μmol) are added and the resulting mixture is heated for 1 hour at 120° C. in a Biotage microwave machine. The reaction medium is evaporated under reduced pressure. The residue is chromatographed on silica gel, eluting with a DCM/MeOH mixture from (100/0 v/v) up to (98/2 v/v) to give 180 mg of 1-(3-difluoromethoxyphenyl)-3-{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]phenyl}urea.

Workup

  1. temperaturethe resulting mixture is heated for 1 hour at 120° C. in a Biotage microwave machine
  2. customThe reaction medium is evaporated under reduced pressure
  3. customThe residue is chromatographed on silica gel
  4. washeluting with a DCM/MeOH mixture from (100/0 v/v) up to (98/2 v/v)

Sources & evidence

ORD record
ord-637fa3637353482c966ad497c8bb1b13
Source dataset
uspto-grants-2015_09
Patent number
US09120812B2

Reaction notes

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