Acetyl chloride → 1-(4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone

HRID 473711Notes

Reaction equation

HRID 473711 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[CH:33]=[CH:32][C:11]([O:12][C:13]2[C:14]([C:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27]C(C)(C)C)=O)[CH2:21][CH:20]=3)=[N:15][CH:16]=[CH:17][N:18]=2)=[CH:10][CH:9]=1.[C:34](Cl)(=O)C>>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[CH:9]=[CH:10][C:11]([O:12][C:13]2[C:14]([C:19]3[CH2:24][CH2:23][N:22]([C:25](=[O:27])[CH3:34])[CH2:21][CH:20]=3)=[N:15][CH:16]=[CH:17][N:18]=2)=[CH:32][CH:33]=1

Participants

3

Reactant 2

HCID 6367Acetyl chlorideHCID 59374036tert-butyl 4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 593742471-(4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone

Procedure

During a resynthesis of Example 279 (Step 1) an incomplete hydrogenation resulted in a small fraction of tert-butyl 4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Example 278) to be carried forward through Example 279 (Step 2), which was subsequently treated in similar fashion using acetyl chloride. The impurity was separated from the major product by SFC using MeOH (1% diethyl amine) to give 1-(4-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone as a white solid. MS (ESI, pos. ion) m/z: 388.1 (M+1). IC50 (uM) 0.00234.

Workup

  1. customDuring a resynthesis of Example 279 (Step 1) an incomplete hydrogenation
  2. additionwas subsequently treated in similar fashion
  3. customThe impurity was separated from the major product by SFC

Sources & evidence

ORD record
ord-997b6b45759647e883897c71ade04207
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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