Triethylamine → 1-Piperidinecarboxylic acid, ethyl ester

HRID 388568

Reaction equation

HRID 388568 reaction equation
ClC1C(NC2C=CC=CC=2S(C(C)C)(=O)=O)=NC(NC2C=C3C(CN([CH:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)C3=O)=CC=2OC(C)C)=NC=1.C(N(CC)CC)C.Cl[C:50]([O:52][CH2:53][CH3:54])=[O:51]>CN(C=O)C>[CH2:53]([O:52][C:50]([N:22]1[CH2:21][CH2:20][CH2:19][CH2:24][CH2:23]1)=[O:51])[CH3:54]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 24816438HCID 24816438, compound

Product 1

HCID 213991-Piperidinecarboxylic acid, ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 6-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-5-isopropoxy-2-piperidin-4-yl-2,3-dihydro-isoindol-1-one (Example 1, 15 mg, 0.025 mmol) and triethylamine (37.5 uL, 0.25 mmol) in DMF (0.5 mL), is added ethyl chloroformate (5.4 mg, 0.05 mmol). The mixture is stirred at room temperature for 1 hour. The crude reaction mixture is purified by mass-trigger preparative RP LC-MS to afford the title compound 446-{5-chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-5-isopropoxy-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-1-carboxylic acid ethyl ester (175) as a white solid. 1H NMR 400 MHz (DMSO-d6 with trace D2O) δ 8.55 (d, 1H), 8.32 (s, 1H), 8.14 (s, 1H), 7.82 (dd, 1H), 7.74 (t, 1H), 7.34 (t, 1H), 7.28 (s, 1H), 4.73 (m, 2H), 4.39 (s, 2H), 4.12 (m, 2H), 4.06 (q, 2H), 3.46 (m, 1H), 2.92 (m 2H), 1.76 (m, 2H), 1.68 (m, 2H), 1.29 (d, 6H), 1.20 (t, 3H), 1.17 (d, 6H); MS m/z 671 (M+1).

Workup

  1. customThe crude reaction mixture
  2. customis purified by mass-trigger preparative RP LC-MS

Sources & evidence

ORD record
ord-7f2c3fac5fda466c9cfad08f2d382125
Source dataset
uspto-grants-2013_02
Patent number
US08377921B2

Linked notes

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