Morpholine → HCID 178491852, compound

HRID 1435337Notes

Reaction equation

HRID 1435337 reaction equation
[NH2:1][C:2]1[C:7]([C:8](=[O:19])[C:9]2[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[C:11]([F:17])[C:10]=2[F:18])=[CH:6][N:5]=[C:4]([NH:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([NH:27][S:28]([CH2:31][CH2:32][CH2:33]Cl)(=[O:30])=[O:29])[CH2:23][CH2:22]2)[N:3]=1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>O1CCCC1>[NH2:1][C:2]1[C:7]([C:8](=[O:19])[C:9]2[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[C:11]([F:17])[C:10]=2[F:18])=[CH:6][N:5]=[C:4]([NH:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([NH:27][S:28]([CH2:31][CH2:32][CH2:33][N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)(=[O:30])=[O:29])[CH2:23][CH2:22]2)[N:3]=1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 178491850HCID 178491850, compound

Product 1

HCID 178491852HCID 178491852, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-chloro-propane-1-sulfonic acid [4-[4-amino-5-(2,3-difluoro-6-methoxy-benzoyl)-pyrimidin-2-ylamino]-cyclohexyl]-amide (104 mg, 0.20 mmol, Example 293) in tetrahydrofuran (5 mL), morpholine (100 mg, 1.15 mmol, Aldrich) was added and the mixture was heated at reflux for 24 hours. The reaction was quenched with water and the mixture was extracted with ethyl acetate (3×5 mL). The extracts were combined and dried with sodium sulfate and concentrated. The residue was chromatographed (8% 9N ammonia in methanol/dichloromethane) to give a pale yellow solid. 57 mg, 50%. MS (ES) MH+=569. CDK4 IC50=0.015 μM; CDK1 IC50=0.008 μM; CDK2 IC50=0.005 μM; HCT 116 IC90=0.374 μM.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 24 hours
  3. customThe reaction was quenched with water
  4. extractionthe mixture was extracted with ethyl acetate (3×5 mL)
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was chromatographed (8% 9N ammonia in methanol/dichloromethane)
  8. customto give a pale yellow solid

Sources & evidence

ORD record
ord-0a26a56de797470eb9ae5143b9ab7d3a
Source dataset
uspto-grants-2009_11
Patent number
US07615634B2

Reaction notes

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