Diisopropylethylamine → 7-[2-(4-Fluoro-benzylamino)-benzoylamino]-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 969673Notes

Reaction equation

HRID 969673 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][NH:7][C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10]([OH:12])=O)=[CH:4][CH:3]=1.[C:19]([O:23][C:24]([N:26]1[CH2:35][C:34]([CH3:37])([CH3:36])[C:33]2[C:28](=[CH:29][C:30]([NH2:38])=[CH:31][CH:32]=2)[CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:19]([O:23][C:24]([N:26]1[CH2:35][C:34]([CH3:37])([CH3:36])[C:33]2[C:28](=[CH:29][C:30]([NH:38][C:10](=[O:12])[C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=3[NH:7][CH2:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:18][CH:17]=3)=[CH:31][CH:32]=2)[CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 21786232HCID 21786232, compoundHCID 21959561Tert-butyl 7-amino-4,4-dimethyl-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 695108657-[2-(4-Fluoro-benzylamino)-benzoylamino]-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The mixture of 2-(4-fluorobenzylamino)benzoic acid (Step A, 0.7 g, 1.20 mmol), 7-amino-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (0.71 g, 2.57 mmol), TBTU (0.917 g, 2.86 mmol), and DIEA (0.5 mL) in 30 mL of CH2Cl2 was stirred at RT for 2 h, then diluted with more CH2Cl2. The organic layer was washed with water, and brine, dried with MgSO4, filtered, and condensed. The residue was purified by flash column chromatography (0 to 30% of EtOAc in CH2Cl2), and the titled compound was obtained as oil. MS (ES+): 504 (M+H)+. Calc'd for C30H34FN3O3-503.26.

Workup

  1. washThe organic layer was washed with water, and brine
  2. dry with materialdried with MgSO4
  3. filtrationfiltered
  4. customcondensed
  5. customThe residue was purified by flash column chromatography (0 to 30% of EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-88de52d703214a58a6274f6b7694e780
Source dataset
uspto-grants-2007_12
Patent number
US07307088B2

Reaction notes

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