Water → 6-(Piperidin-4-yloxy)-isoquinoline-5-carboxylic acid ethyl ester

HRID 1022869Notes

Reaction equation

HRID 1022869 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:16](I)=[C:17]3[C:22](=[CH:23][CH:24]=2)[CH:21]=[N:20][CH:19]=[CH:18]3)[CH2:10][CH2:9]1)=O)(C)(C)C.C(N(CC)CC)C.O.[C:34]([O:37][CH2:38][CH3:39])(=[O:36])C>CN(C1C=CN=CC=1)C.C(O)C.[Pd]>[CH2:38]([O:37][C:34]([C:16]1[C:17]2[CH:18]=[CH:19][N:20]=[CH:21][C:22]=2[CH:23]=[CH:24][C:15]=1[O:14][CH:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1)=[O:36])[CH3:39]

Participants

8

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 576467514-(5-Iodo-isoquinoline-6-yloxy)-piperidin-1-carboxylic acid tert-butyl ester

Product 1

HCID 576469616-(Piperidin-4-yloxy)-isoquinoline-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of 200 mg (0.44 mmol) 4-(5-iodo-isoquinoline-6-yloxy)-piperidin-1-carboxylic acid tert-butyl ester (12), 107 mg (0.88 mmol) of DMAP, 4.7 mg (0.1 eq) of Pd on charcoal (10%), 150 μL (0.88 mmol) of triethyl amine and 58 mg (0.22 mmol) of Mo(CO)6 in 3 mL of ethanol was heated to 135° C. for 1 h in a microwave reactor (CEM Discovery). Then water and ethyl acetate were added and the mixture was filtered through a Celite cartridge. After removal of the solvents the remainder was subjected to preparative HPLC to give the 7.4 mg Boc-protected intermediate. To remove the Boc group the intermediate was treated with 2 mL 5-6 N HCl in isopropanol at room temperature for 2 h. Purification by preparative HPLC gave 2.5 mg of compound 30 as TFA salt.

Workup

  1. filtrationthe mixture was filtered through a Celite cartridge
  2. customAfter removal of the solvents the remainder
  3. customto give the 7.4 mg Boc-
  4. customTo remove the Boc group the intermediate
  5. additionwas treated with 2 mL 5-6 N HCl in isopropanol at room temperature for 2 h
  6. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-e95ad064024e4d50addc5fca2c22c8d1
Source dataset
uspto-grants-2014_05
Patent number
US08722671B2

Reaction notes

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