Morpholine → HCID 86605112, compound

HRID 545102Notes

Reaction equation

HRID 545102 reaction equation
[F-].[Cs+].Cl[C:4]1[N:9]=[N:8][C:7]([C:10]2[N:19]=[C:18]3[C:13]([C:14]([NH:20][C:21]4[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][N:22]=4)=[CH:15][CH:16]=[N:17]3)=[CH:12][CH:11]=2)=[C:6]([C:31]([F:34])([F:33])[F:32])[CH:5]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.C([O-])(O)=O.[Na+]>CN(C)C(=O)C.CCOC(C)=O.CS(C)=O>[N:35]1([C:4]2[N:9]=[N:8][C:7]([C:10]3[N:19]=[C:18]4[C:13]([C:14]([NH:20][C:21]5[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][N:22]=5)=[CH:15][CH:16]=[N:17]4)=[CH:12][CH:11]=3)=[C:6]([C:31]([F:34])([F:33])[F:32])[CH:5]=2)[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 25953Cesium fluoride2×HCID 516892Sodium BicarbonateHCID 86605110HCID 86605110, compound

Product 1

HCID 86605112HCID 86605112, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

Place CsF (50 mg, 0.33 mmol) in an empty flask. Dissolve 7-[6-chloro-4-(trifluoromethyl)pyridazin-3-yl]-N-[5-(trifluoromethyl)pyridin-2-yl]-1,8-naphthyridin-4-amine (19 mg, 0.04 mmol) in N,N-dimethylacetamide (0.2 mL) and add to the CsF. Next, add a solution of morpholine (0.2M toluene, 0.24 mL) and DMSO (0.2 mL). Heat the mixture overnight at 80° C. Cool to room temperature and add EtOAc (1 mL) and sat. NaHCO3 (aq) (1 mL). Extract the organic layer and place directly on an SCX ion-exchange column. First, wash the column with EtOAc/MeOH (90/10). Discard this solution. Wash the column with EtOAc/MeOH/N(Et)3 (90/10/5). Collect and evaporate the wash to yield the title compound. 1H NMR (CDCl3) δ 9.59 (s, 1H), 9.43 (br s, 1H), 9.10 (d, 1H), 8.90 (d, 1H), 8.72 (br s, 1H), 7.90 (dd, 1H), 7.30 (s, 1H), 7.15 (d, 1H), 3.93 (m, 2H), 3.89 (m, 2H). LC/MS (MH+) 523.01. The IC50 determined as described in Example 6 is less than 1 micromolar.

Workup

  1. temperatureCool to room temperature
  2. extractionExtract the organic layer and place directly on an SCX ion-exchange column
  3. washFirst, wash the column with EtOAc/MeOH (90/10)
  4. washWash the column with EtOAc/MeOH/N(Et)3 (90/10/5)
  5. customCollect
  6. customevaporate the
  7. washwash

Sources & evidence

ORD record
ord-afb993115bb64b85a1420e5d2c17e52a
Source dataset
uspto-grants-2011_05
Patent number
US07935702B2

Reaction notes

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