Isopropyl chloroformate → 4-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-ylamino]-piperidine-1-carboxylic acid isopropyl ester

HRID 448566Notes

Reaction equation

HRID 448566 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[N:19]=[CH:18][N:17]=[C:16]([NH:20][CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[CH:15]=1)[CH2:9][CH2:8]2)(=[O:4])=[O:3].C(N(CC)CC)C.Cl[C:35]([O:37][CH:38]([CH3:40])[CH3:39])=[O:36]>C(Cl)Cl>[CH:38]([O:37][C:35]([N:24]1[CH2:25][CH2:26][CH:21]([NH:20][C:16]2[CH:15]=[C:14]([N:10]3[C:11]4[C:7](=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:13][CH:12]=4)[CH2:8][CH2:9]3)[N:19]=[CH:18][N:17]=2)[CH2:22][CH2:23]1)=[O:36])([CH3:40])[CH3:39]

Participants

5

Reactant 3

HCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 66894566[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-yl]-piperidin-4-yl-amine

Product 1

HCID 498487854-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-ylamino]-piperidine-1-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6c (104 mg, 0.21 mmol) and triethylamine (0.1 mL, 3.3 eq) in 1 mL of DCM, was added isopropyl chloroformate (0.24 mL, 1.1 eq). The mixture was stirred at room temperature for 2 h. The crude mixture was poured onto silica and eluted with ethyl acetate/hexane then chromatographed over a silica gel column (elution with 25-100% ethyl acetate and 0.1% TEA in hexanes) and finally purified on preparative HPLC to give 6-1, LC-MS 460.4 (MH+), tR=4.50 (Method 4). EC50: 611 nM.

Workup

  1. washeluted with ethyl acetate/hexane
  2. customthen chromatographed over a silica gel column (elution with 25-100% ethyl acetate and 0.1% TEA in hexanes)
  3. customfinally purified on preparative HPLC
  4. customto give 6-1, LC-MS 460.4 (MH+), tR=4.50 (Method 4)

Sources & evidence

ORD record
ord-438ef55a13814e368e146a552abb8ff7
Source dataset
uspto-grants-2013_07
Patent number
US08481731B2

Reaction notes

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