1,2-Dichloroethane → tert-Butyl 4-((3-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methylphenyl)ethynyl)piperidine-1-carboxylate

HRID 1469170Notes

Reaction equation

HRID 1469170 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[C:15][C:16]2[CH:17]=[C:18]([N:26]([CH2:33][CH3:34])[CH:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[C:19]([CH3:25])=[C:20]([CH:24]=2)[C:21](O)=[O:22])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[Cl-].[CH3:43][C:44]1[CH:49]=[C:48]([CH3:50])[NH:47][C:46](=[O:51])[C:45]=1[CH2:52][NH3+:53].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CS(C)=O>[CH3:43][C:44]1[CH:49]=[C:48]([CH3:50])[NH:47][C:46](=[O:51])[C:45]=1[CH2:52][NH:53][C:21]([C:20]1[CH:24]=[C:16]([C:15]#[C:14][CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[CH:17]=[C:18]([N:26]([CH2:33][CH3:34])[CH:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[C:19]=1[CH3:25])=[O:22]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 867155755-((1-(tert-Butoxycarbonyl)piperidin-4-yl)ethynyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoic acidHCID 178425248HCID 178425248, compound

Product 1

HCID 86715576tert-Butyl 4-((3-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methylphenyl)ethynyl)piperidine-1-carboxylateYield 98%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 5-((1-(tert-butoxycarbonyl)piperidin-4-yl)ethynyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoic acid (1.06 g, 2.25 mmol) in DMSO (5.8 mL) at rt was added triethylamine (0.90 mL, 6.44 mmol) and (4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methanaminium chloride (0.405 g, 2.15 mmol). The clear solution become heterogenous. Then HOBT (0.493 g, 3.22 mmol) and EDC (0.617 g, 3.22 mmol) were added and the resulting reaction mixture was stirred at rt overnight. The reaction was quenched with water (80 mL) and the slurry was stirred for 1 h at rt. The slurry was filtrated and the cake was washed with water (2×20 mL). The collected solid was dried under vacuum to give the titled compound (1.27 g, 98% yield). 1H-NMR (500 MHz, CD3OD) 8 ppm; 7.22 (s, 1H), 7.08 (d, J=1.0 Hz 1H), 6.11 (s, 1H), 4.45 (s, 2H), 3.92 (brd, J=10.8 Hz, 2H), 3.78 (dd, J=4.4, 5.4 Hz, 1H), 3.75 (dd, J=4.4, 5.4 Hz, 1H), 3.36 (t, J=11.7 Hz, 2H), 3.21 (br t, J=8.3 Hz, 2H), 3.07 (q, J=7.3 Hz, 2H), 3.01 (dddd, J=3.9, 3.9, 11.3, 11.3 Hz, 1H), 2.84 (dddd, J=3.4, 3.4. 3.9, 3.9 Hz, 1H), 2.38 (s, 3H), 2.28 (s, 3H), 2.25 (s, 3H), 1.88 (m, 2H), 1.70 ((brd, J=12.2 Hz, 2H), 1.60 (m, 4H), 1.47 (s, 9H), 0.87 (t, J=7.3 Hz, 3H); MS (ESI) [M+H]+605.6.

Workup

  1. customthe resulting reaction mixture
  2. customThe reaction was quenched with water (80 mL)
  3. stirringthe slurry was stirred for 1 h at rt
  4. filtrationThe slurry was filtrated
  5. washthe cake was washed with water (2×20 mL)
  6. customThe collected solid was dried under vacuum

Sources & evidence

ORD record
ord-5732207f5e934a7cae706036e06652ed
Source dataset
uspto-grants-2015_04
Patent number
US09006242B2

Reaction notes

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