Dimethylformamide → HCID 89714897, compound

HRID 2273075Notes

Reaction equation

HRID 2273075 reaction equation
C1([O:7][C:8](=O)[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][N:46]1[CH:50]=[CH:49][C:48]([NH2:51])=[N: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:12]=[CH:11][C:10]([NH:9][C:8]([NH:51][C:48]4[CH:49]=[CH:50][N:46]([CH3:45])[N:47]=4)=[O:7])=[CH:15][CH:14]=3)[C:26]=2[C:25](=[O:27])[N:24]([CH:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[CH2:23]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 1372541-Methyl-3-aminopyrazole2×HCID 89714600HCID 89714600, compound

Product 1

HCID 89714897HCID 89714897, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

50 mg (83.4 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 (26 μmol) of 1-methyl-1H-pyrazol-3-ylamine are added. 1 ml of DMF and 2 ml of THF are added. The reactor is heated in a Biotage microwave machine for 30 minutes at 100° C. 100 mg (100 μmol) of 1-methyl-1H-pyrazol-3-ylamine are added and the mixture is heated for 2 hours at 110° C. The solvents are evaporated off. 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 a solid, which is then washed with water and dried. 23 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-(1-methyl-1H-pyrazol-3-yl)urea are recovered.

Workup

  1. temperaturethe mixture is heated for 2 hours at 110° C
  2. customThe solvents are evaporated off
  3. customThe residue is chromatographed on silica gel
  4. washeluting with an MeOH/DCM mixture from (0/100 v/v) up to (5/95 v/v)
  5. customto give a solid, which
  6. washis then washed with water
  7. customdried
  8. custom23 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-(1-methyl-1H-pyrazol-3-yl)urea are recovered

Sources & evidence

ORD record
ord-49a7660a20044346b0b2577addc54ab9
Source dataset
uspto-grants-2015_09
Patent number
US09120812B2

Reaction notes

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