Diisopropylethylamine → 4-[6-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1786472Notes

Reaction equation

HRID 1786472 reaction equation
Cl.[Cl:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[C:8]([C:12]([OH:14])=O)[NH:9]2)=[CH:5][C:4]=1[O:15][CH:16]1[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]1.[Cl-].[Li+].[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([C:12]([C:8]2[NH:9][C:10]3[C:6]([CH:7]=2)=[CH:5][C:4]([O:15][CH:16]2[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]2)=[C:3]([Cl:2])[CH:11]=3)=[O:14])[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:28])[CH3:29]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 433294Lithium ChlorideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 670179056-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1h-indole-2-carboxylic acid hydrochloride salt

Product 1

HCID 685649604-[6-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl esterYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid hydrochloride salt with 1 eq. lithium chloride (760 mg, 1.0 eq.), tert-butyl-1-piperazinecarboxylate (467 mg, 1.25 eq.), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (838 mg, 1.25 eq.) and N,N-diisopropylethylamine (2.43 mL, 7 eq.) in N,N-dimethylformamide (9 mL) was stirred at room temperature for 20 h. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous sodium hydrogencarbonate solution. The organic layer was separated and washed with water and brine, and dried over sodium sulfate, filtered and the solvents were removed in vacuo. The residue was purified by flash chromatography on silica gel with a 19:1:0 to 90:9:1 gradient of dichloromethane/methanol/ammonia as eluant, to afford 577 mg (57%) of the title compound as a light-yellow solid.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvents were removed in vacuo
  7. customThe residue was purified by flash chromatography on silica gel with a 19:1:0 to 90:9:1 gradient of dichloromethane/methanol/ammonia as eluant

Sources & evidence

ORD record
ord-738d11a3f8a34cebbe5ca2ff2b99cedf
Source dataset
uspto-grants-2009_03
Patent number
US07507736B2

Reaction notes

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