Methyl chloroformate → 3-[4-Amino-5-(2-methoxy-benzoyl)-pyrimidin-2-ylamino]-piperidine-1-carboxylic acid methyl ester

HRID 1371617Notes

Reaction equation

FC(F)(F)C(O)=O.[NH2:8][C:9]1[C:14]([C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23][CH3:24])=[O:16])=[CH:13][N:12]=[C:11]([NH:25][CH:26]2[CH2:31][CH2:30][CH2:29][NH:28][CH2:27]2)[N:10]=1.C(N(CC)CC)C.Cl[C:40]([O:42][CH3:43])=[O:41]>ClCCl>[CH3:43][O:42][C:40]([N:28]1[CH2:29][CH2:30][CH2:31][CH:26]([NH:25][C:11]2[N:10]=[C:9]([NH2:8])[C:14]([C:15](=[O:16])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[O:23][CH3:24])=[CH:13][N:12]=2)[CH2:27]1)=[O:41]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of [4-amino-2-(piperidin-3-ylamino)-pyrimidin-5-yl]-(2-methoxy-phenyl)-methanone trifluoroacetic acid salt (42 mg, Example 53) in dichloromethane (3 mL) were added triethylamine (48 mg, Aldrich) and methyl chloroformate (6.1 mg, Aldrich) at 0° C. After stirring for 1 hour at 0° C., the reaction mixture was concentrated in vacuo and crude product was purified on silica gel with 95:5 of dichloromethane/methanol to give 3-[4-amino-5-(2-methoxy-benzoyl)-pyrimidin-2-ylamino]-piperidine-1-carboxylic acid methyl ester (20.5 mg). MS (M+H)+, 386. CDK4 IC50=0.459 μM; CDK1 IC50=0.469 μM; CDK2 IC50=0.713 μM; HCT 116 IC90=6.437 μM.

Workup

concentrationthe reaction mixture was concentrated in vacuo and crude product
customwas purified on silica gel with 95:5 of dichloromethane/methanol

Sources & evidence

ORD record: ord-4f4ca7b5af3b45f4bd6e4940ca891d76
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07157455B2

Reaction notes

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