(3S)-3-methylmorpholine → HCID 89714803, compound

HRID 2273063Notes

Reaction equation

HRID 2273063 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:24]3[C:23](=[O:25])[N:22]([CH2:26][CH3:27])[CH2:21][C:20]([CH3:29])([CH3:28])[O:19][C:18]=3[N:17]=[C:16](S(C)(=O)=O)[N:15]=2)=[CH:10][C:9]=1[F:34])([CH3:4])([CH3:3])[CH3:2].[CH3:36][C@H:37]1[CH2:42][O:41][CH2:40][CH2:39][NH:38]1>O1CCOCC1>[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:24]3[C:23](=[O:25])[N:22]([CH2:26][CH3:27])[CH2:21][C:20]([CH3:29])([CH3:28])[O:19][C:18]=3[N:17]=[C:16]([N:38]3[CH2:39][CH2:40][O:41][CH2:42][C@@H:37]3[CH3:36])[N:15]=2)=[CH:10][C:9]=1[F:34])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 12012220(3S)-3-methylmorpholineHCID 89714551HCID 89714551, compound

Product 1

HCID 89714803HCID 89714803, compoundYield 35.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2.5 g of [4-(6-ethyl-2-methanesulfonyl-8,8-dimethyl-5-oxo-5,6,7,8-tetrahydro-9-oxa-1,3,6-triazabenzocyclohepten-4-yl)-2-fluorophenyl]carbamic acid tert-butyl ester (19.66 mmol) in 20 ml of dioxane are placed in 4 microwave tubes, respectively. One quarter of (S)-3-methylmorpholine (98.32 mmol) is added to each tube, respectively. The tubes are heated for 2 hours at 100° C. in a Biotage microwave machine. The reaction media are filtered and rinsed with MeOH. The solid is washed with water, with acetonitrile and then with pentane. 3.7 g of {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]-2-fluorophenyl}carbamic acid tert-butyl ester are obtained. The DMSO/MeOH phase is evaporated to dryness. The residue is taken up in water and filtered, rinsed with acetonitrile and then with pentane. This product is chromatographed on silica gel with a gradient of MeOH in DCM ranging from 0 to 5%. 1.7 g of {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]-2-fluorophenyl}carbamic acid tert-butyl ester are obtained.

Workup

  1. customThe reaction media
  2. filtrationare filtered
  3. washrinsed with MeOH
  4. washThe solid is washed with water, with acetonitrile

Sources & evidence

ORD record
ord-f0a7932af94e41829fc1d22f1947c2e9
Source dataset
uspto-grants-2015_09
Patent number
US09120812B2

Reaction notes

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