Diisopropylethylamine → N-(trans-2-((2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)methyl)cyclohexyl)-2-methoxyethanamide

HRID 74915Notes

Reaction equation

HRID 74915 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:8][NH:9][C:10]1[C:15]([F:16])=[CH:14][N:13]=[C:12]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([Cl:26])[CH:24]=3)[N:19](S(C3C=CC(C)=CC=3)(=O)=O)[CH:18]=2)[N:11]=1.CCN(C(C)C)C(C)C.[CH3:46][O:47][CH2:48][C:49](Cl)=[O:50]>C(Cl)Cl>[Cl:26][C:23]1[CH:24]=[C:25]2[C:17]([C:12]3[N:11]=[C:10]([NH:9][CH2:8][C@@H:3]4[CH2:4][CH2:5][CH2:6][CH2:7][C@H:2]4[NH:1][C:49](=[O:50])[CH2:48][O:47][CH3:46])[C:15]([F:16])=[CH:14][N:13]=3)=[CH:18][NH:19][C:20]2=[N:21][CH:22]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 96623Methoxyacetyl chlorideHCID 68007392N-((trans-2-aminocyclohexyl)methyl)-2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-amine

Product 1

HCID 68007215N-(trans-2-((2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)methyl)cyclohexyl)-2-methoxyethanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled mixture of N-((trans-2-aminocyclohexyl)methyl)-2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-amine (0.060 g, 0.093 mmol) and iPr2NEt (0.057 mL, 0.330 mmol) in CH2Cl2 (2 mL) at 0° C., was added 2-methoxyacetyl chloride (0.010 g, 0.098 mmol). After 5 min, the solution was allowed to warm to room temperature. After 3 hours, the mixture was concentrated in vacuo, taken up in THF (1 mL) and treated with LiOH (0.326 mL, 1.0 M solution) at 120° C. for 10 min. The resulting mixture was cooled to room temperature and partitioned and the aqueous layer extracted with EtOAc and the combined organics were concentrated in vacuo. Preparative HPLC provided the desired product, 556, as a racemic mixture of TFA salts (8.6 mg, 17% yield).

Workup

  1. waitAfter 3 hours
  2. concentrationthe mixture was concentrated in vacuo
  3. additiontreated with LiOH (0.326 mL, 1.0 M solution) at 120° C. for 10 min
  4. temperatureThe resulting mixture was cooled to room temperature
  5. custompartitioned
  6. extractionthe aqueous layer extracted with EtOAc
  7. concentrationthe combined organics were concentrated in vacuo

Sources & evidence

ORD record
ord-66bb95f3ace544baa955b6711a2666a3
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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