Triethylamine → Methyl 4-[(2S,4R)-1-acetyl-2-methyl-4-(3-pyridinylamino)-1,2,3,4-tetrahydro-6-quinolinyl]-3-methylbenzoate

HRID 2041781Notes

Reaction equation

HRID 2041781 reaction equation
[CH3:1][O:2][C:3](=[O:26])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]([C:20](=[O:22])[CH3:21])[C@@H:15]([CH3:23])[CH2:14][C@H:13]3[NH2:24])=[C:6]([CH3:25])[CH:5]=1.C(N(CC)CC)C.[N:34]1[CH:39]=[CH:38][CH:37]=[C:36](B(O)O)[CH:35]=1.B(O)O.O.N>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[NH3:16].[C:20]([N:16]1[C:17]2[C:12](=[CH:11][C:10]([C:7]3[CH:8]=[CH:9][C:4]([C:3]([O:2][CH3:1])=[O:26])=[CH:5][C:6]=3[CH3:25])=[CH:19][CH:18]=2)[C@H:13]([NH:24][C:36]2[CH:35]=[N:34][CH:39]=[CH:38][CH:37]=2)[CH2:14][C@@H:15]1[CH3:23])(=[O:22])[CH3:21]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 61668Boronic AcidHCID 27343783-Pyridinylboronic acid2×HCID 12896473Azane;hydrateHCID 67206975Methyl-4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]-3-methylbenzoate

Product 2

HCID 222AmmoniaHCID 67206073Methyl 4-[(2S,4R)-1-acetyl-2-methyl-4-(3-pyridinylamino)-1,2,3,4-tetrahydro-6-quinolinyl]-3-methylbenzoateYield 50%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Methyl-4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]-3-methylbenzoate (for a preparation see Intermediate 96) (40 mg, 0.113 mmol) was dissolved in dichloromethane (DCM) (1.5 mL) and treated with copper(II) acetate (30.9 mg, 0.170 mmol) and triethylamine (0.047 mL, 0.340 mmol) The resulting mixture was stirred at room temperature for a few minutes then pyridine-3-boronic acid (41.9 mg, 0.340 mmol) was added. After 5 h, further boronic acid (3.5 mg, 0.028 mmol, 0.25 eq) was added and the mixture stirred at room temperature. The stirring was continued for 7 days with 10 additions of pyridine-3-boronic acid (41.9 mg, 0.340 mmol) at regular intervals (except on day 4 and day 5). The reaction mixture was then treated with a 3:1 water/ammonia 0.88 (1 mL), then was stirred for 10 min before being diluted with DCM (20 mL). The layers were separated and the organic phase was washed with a saturated NaHCO3 aqueous solution. The combined aqueous phases were extracted with DCM (20 mL). The combined organic phases were dried using a hydrophobic frit and then concentrated in vacuo. Purification of the residue on SP4 using a 10 G silica cartridge (gradient:50 to 100% AcOEt in Hexanes then 0 to 10% (2M NH3 in MeOH) in DCM) gave Methyl 4-[(2S,4R)-1-acetyl-2-methyl-4-(3-pyridinylamino)-1,2,3,4-tetrahydro-6-quinolinyl]-3-methylbenzoate (25 mg, 50%) as a yellow oil.

Workup

  1. stirringthe mixture stirred at room temperature
  2. stirringwas stirred for 10 min
  3. customThe layers were separated
  4. washthe organic phase was washed with a saturated NaHCO3 aqueous solution
  5. extractionThe combined aqueous phases were extracted with DCM (20 mL)
  6. customThe combined organic phases were dried
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue on SP4

Sources & evidence

ORD record
ord-53594c3755a64beba313157404ce8ecb
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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