Dimethylformamide → HCID 89714584, compound

HRID 2273074Notes

Reaction equation

HRID 2273074 reaction equation
C1(O[C:8](=[O:44])[NH:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:26]4[C:25](=[O:27])[N:24]([CH:28]5[CH2:33][CH2:32][O:31][CH2:30][CH2:29]5)[CH2:23][C:22]([CH3:35])([CH3:34])[O:21][C:20]=4[N:19]=[C:18]([N:36]4[CH2:42][CH:41]5[O:43][CH:38]([CH2:39][CH2:40]5)[CH2:37]4)[N:17]=3)=[CH:12][CH:11]=2)C=CC=CC=1.[CH3:45][C:46]1[O:50][N:49]=[C:48]([NH2:51])[CH:47]=1.CN(C=O)C>C1COCC1>[CH3:35][C:22]1([CH3:34])[O:21][C:20]2[N:19]=[C:18]([N:36]3[CH2:37][CH:38]4[O:43][CH:41]([CH2:40][CH2:39]4)[CH2:42]3)[N:17]=[C:16]([C:13]3[CH:14]=[CH:15][C:10]([NH:9][C:8]([NH:51][C:48]4[CH:47]=[C:46]([CH3:45])[O:50][N:49]=4)=[O:44])=[CH:11][CH:12]=3)[C:26]=2[C:25](=[O:27])[N:24]([CH:28]2[CH2:29][CH2:30][O:31][CH2:32][CH2:33]2)[CH2:23]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 661723-Amino-5-methylisoxazole3×HCID 89714600HCID 89714600, compound

Product 1

HCID 89714584HCID 89714584, compoundYield 11.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

50 mg (83.38 μmol) of {4-[8,8-dimethyl-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-5-oxo-6-(tetrahydropyran-4-yl)-5,6,7,8-tetrahydro-9-oxa-1,3,6-triazabenzocyclohepten-4-yl]phenyl}carbamic acid phenyl ester are placed in a microwave reactor and 25 mg (0.25 mmol) of 5-methylisoxazol-3-ylamine are added. 2 ml of DMF and 1 ml of THF are added. The reaction mixture is heated in a Biotage microwave machine for 30 minutes at 100° C. 100 mg (1.0 mmol) of 5-methylisoxazol-3-ylamine are added and the mixture is heated for 2 hours at 110° C. A further 300 mg (3 mmol) of 5-methylisoxazol-3-ylamine are added and the mixture is heated for 2 hours at 110° C. The solvents are evaporated off. The residue is taken up in water and the insoluble material is filtered off, washed three times with water, taken up in MeOH/DCM and dried. The residue is chromatographed on silica gel, eluting with an MeOH/DCM mixture from (0/100 v/v) up to (5/95 v/v) to give 6 mg of 1-{4-[8,8-dimethyl-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-5-oxo-6-(tetrahydropyran-4-yl)-5,6,7,8-tetrahydro-9-oxa-1,3,6-triazabenzocyclohepten-4-yl]phenyl}-3-(5-methylisoxazol-3-yl)urea.

Workup

  1. temperaturethe mixture is heated for 2 hours at 110° C
  2. temperaturethe mixture is heated for 2 hours at 110° C
  3. customThe solvents are evaporated off
  4. filtrationthe insoluble material is filtered off
  5. washwashed three times with water
  6. customdried
  7. customThe residue is chromatographed on silica gel
  8. washeluting with an MeOH/DCM mixture from (0/100 v/v) up to (5/95 v/v)

Sources & evidence

ORD record
ord-ef3140836ef348d38fa15cbdfd58423f
Source dataset
uspto-grants-2015_09
Patent number
US09120812B2

Reaction notes

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