Diisopropylethylamine → tert-butyl 1-((7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl)-6-(methoxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 2202286Notes

Reaction equation

HRID 2202286 reaction equation
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[C:19]([O:23][C:24]([N:26]1[CH2:35][CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([CH2:36][O:37][CH3:38])[CH:32]=2)[CH:27]1[C:39](O)=[O:40])=[O:25])([CH3:22])([CH3:21])[CH3:20].[F:42][C:43]1[CH:44]=[C:45]([NH2:54])[CH:46]=[C:47]2[C:51]=1[C:50]([CH3:53])([CH3:52])[CH2:49][CH2:48]2.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[F:42][C:43]1[CH:44]=[C:45]([NH:54][C:39]([CH:27]2[C:28]3[C:33](=[CH:32][C:31]([CH2:36][O:37][CH3:38])=[CH:30][CH:29]=3)[CH2:34][CH2:35][N:26]2[C:24]([O:23][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:25])=[O:40])[CH:46]=[C:47]2[C:51]=1[C:50]([CH3:52])([CH3:53])[CH2:49][CH2:48]2

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 1186227042-(Tert-butoxycarbonyl)-6-(methoxymethyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acidHCID 1186227997-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-amine

Product 1

HCID 118622700tert-butyl 1-((7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl)-6-(methoxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 71.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

T3P (8.24 mL, 14.00 mmol) was added to a mixture of 2-(tert-butoxycarbonyl)-6-(methoxymethyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (1.5 g, 4.67 mmol), 7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-amine (0.837 g, 4.67 mmol), DIEA (4.08 mL, 23.34 mmol), DMAP (0.570 g, 4.67 mmol) and ethyl acetate (5 mL) at 60° C., and the mixture was stirred at 60° C. for 2 days. To the reaction mixture was added ethyl acetate, and the mixture was washed with water and brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 32→40% ethyl acetate/hexane) to give tert-butyl 1-((7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl)-6-(methoxymethyl)-3,4-dihydroisoquinoline-2 (1H)-carboxylate (1.600 g, 3.32 mmol, 71.0%) as a white solid.

Workup

  1. washthe mixture was washed with water and brine
  2. dry with materialdried over magnesium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 32→40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-967189d9f70f4e7e83858ea6d426e2d2
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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