Lithium Hexamethyldisilazide → 4-{[(3-bromo-2-chloro-pyridin-4-yl)-(2-chloro-pyridine-4-carbonyl)-amino]-methyl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 2422363Notes

Reaction equation

HRID 2422363 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([O:15][C:16]([N:18]1[CH2:23][CH:22]=[C:21]([CH2:24][NH:25][C:26]2[CH:31]=[CH:30][N:29]=[C:28]([Cl:32])[C:27]=2[Br:33])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].[Cl:34][C:35]1[CH:36]=[C:37]([CH:41]=[CH:42][N:43]=1)[C:38](Cl)=[O:39]>O1CCCC1>[C:11]([O:15][C:16]([N:18]1[CH2:19][CH:20]=[C:21]([CH2:24][N:25]([C:26]2[CH:31]=[CH:30][N:29]=[C:28]([Cl:32])[C:27]=2[Br:33])[C:38]([C:37]2[CH:41]=[CH:42][N:43]=[C:35]([Cl:34])[CH:36]=2)=[O:39])[CH2:22][CH2:23]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 28000032-Chloropyridine-4-carbonyl chlorideHCID 727367364-[(3-Bromo-2-chloro-pyridin-4-ylamino)-methyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Product 1

HCID 866129194-{[(3-bromo-2-chloro-pyridin-4-yl)-(2-chloro-pyridine-4-carbonyl)-amino]-methyl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl esterYield 88.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Lithium bis(trimethylsilyl)amide (1M solution in THF, 3 ml) was added dropwise to a stirred solution of 4-[(3-Bromo-2-chloro-pyridin-4-ylamino)-methyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.53 g) in tetrahydrofuran (20 ml) at −78° C. under N2. The yellow solution was warmed to 0° C. and then 2-chloroisonicotinoyl chloride (50% solution in toluene, 0.95 g) was added. The solution was stirred at 0° C. for 10 min., quenched by addition of aqueous ammonium chloride, extracted with EtOAc, dried (Na2SO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (CH2Cl2 then CH2Cl2/EtOAc 8:2 cyclohexane:ethyl acetate 8:2) to afford 4-{[(3-bromo -2-chloro-pyridin-4-yl)-(2-chloro-pyridine-4-carbonyl)-amino]-methyl }-3,6-dihydro-2H -pyridine-1-carboxylic acid tert-butyl ester (0.63 g), which was identified by its mass and 1H NMR spectra. MS (ES+) 443/445 (MH+—BOC), 484/486 (MH+-isoprene).

Workup

  1. customquenched by addition of aqueous ammonium chloride
  2. extractionextracted with EtOAc
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel chromatography (CH2Cl2

Sources & evidence

ORD record
ord-d10b854125b7447fad9d7a68c171d9a5
Source dataset
uspto-grants-2011_06
Patent number
US07960401B2

Reaction notes

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