Diisopropylethylamine → tert-Butyl 4-{6-[methyl(1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl]pyridin-2-yl}-piperidine-1-carboxylate

HRID 385299

Reaction equation

HRID 385299 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20](O)=[O:21])[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:23][NH:24][C@H:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:28][CH2:27][CH2:26]1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20](=[O:21])[N:24]([CH3:23])[CH:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH2:28][CH2:27][CH2:26]3)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 7128544(R)-N-Methyl-1,2,3,4-tetrahydronaphthalen-1-amineHCID 666866476-(1-(Tert-butoxycarbonyl)piperidin-4-yl)picolinic acid

Product 1

HCID 66686878tert-Butyl 4-{6-[methyl(1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl]pyridin-2-yl}-piperidine-1-carboxylateYield 97.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-6,1′-dicarboxylic acid 1′-tert-butyl ester (150 mg, 0.49 mmol), methyl-(R)-1,2,3,4-tetrahydro-naphthalen-1-yl-amine (0.079 g, 0.49 mmol), and diisopropylethylamine (0.50 mL, 0.49 mmol) in DMF (10 mL) was added dropwise BOP (238 mg, 0.49 mmol) at RT. After stirring overnight at RT, the reaction mixture was poured on water (10 mL) and extracted with ethylacetate (20 mL). The aqueous phase was re-extracted with ethylacetate (20 mL). The combined organic layers were washed with aq. sat. sodium bicarbonate solution (30 mL), 1M HCl solution (30 mL) and brine (30 mL), dried over sodium sulfate, filtered, and evaporated under reduce pressure. The crude mixture was purified by column chromatography on silica gel (ethylacetate/hexane 4:1) to give 6-[methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-carbamoyl]-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (215 mg, 97%). 1H-NMR (400 MHz, CDCl3): δ=1.47 (s, 9H), 1.64-2.05 (m, 8H), 2.18-2.22 (m, 1H), 2.72-2.81 (m, 4H), 2.82 (s, 3H), 4.15-4.25 (m, 2H), 5.15-5.20 (m, 1H), 7.18-7.25 (m, 5H), 7.53-7.71 (m, 1H), 7.73-7.74 (m, 1H).

Workup

  1. additionthe reaction mixture was poured on water (10 mL)
  2. extractionextracted with ethylacetate (20 mL)
  3. extractionThe aqueous phase was re-extracted with ethylacetate (20 mL)
  4. washThe combined organic layers were washed with aq. sat. sodium bicarbonate solution (30 mL), 1M HCl solution (30 mL) and brine (30 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude mixture was purified by column chromatography on silica gel (ethylacetate/hexane 4:1)

Sources & evidence

ORD record
ord-8aaa05e70b20448fbe13165fcd2c0100
Source dataset
uspto-grants-2013_02
Patent number
US08367844B2

Linked notes

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