Dimethylcarbamoyl Chloride → (s)-3-(1-Methylpyrrolidin-2-yl)-4-trimethylsilanyl-4h-pyridine-1-carboxylic acid dimethylamide

HRID 1988107Notes

Reaction equation

HRID 1988107 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][CH:3]1[C:7]1[CH:12]([Si:13]([CH3:16])([CH3:15])[CH3:14])[CH:11]=[CH:10][N:9]([Si](C)(C)C)[CH:8]=1.[CH3:21][N:22]([CH3:26])[C:23](Cl)=[O:24].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:21][N:22]([CH3:26])[C:23]([N:9]1[CH:10]=[CH:11][C@H:12]([Si:13]([CH3:16])([CH3:15])[CH3:14])[C:7]([CH:3]2[CH2:4][CH2:5][CH2:6][N:2]2[CH3:1])=[CH:8]1)=[O:24]

Participants

5

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 516892Sodium BicarbonateHCID 219018773-(1-Methylpyrrolidin-2-yl)-1,4-bis-trimethylsilanyl-1,4-dihydropyridine

Product 1

HCID 66924433(s)-3-(1-Methylpyrrolidin-2-yl)-4-trimethylsilanyl-4h-pyridine-1-carboxylic acid dimethylamideYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3-(1-methylpyrrolidin-2-yl)-1,4-bis-trimethylsilanyl-1,4-dihydropyridine i (0.2 mL, 1.36 mmol) in CH2Cl2 (6 mL) under Ar was added dropwise dimethylcarbamyl chloride (0.19 mL, 2.04 mmol). The reaction mixture was stirred at RT for 1 day. It was then poured into a saturated solution of NaHCO3 (3 mL). The aqueous phase was extracted with CH2Cl2 (5 times). The combined organic layers were washed with water and brine and dried over MgSO4. Evaporation of the solvent under reduced pressure afforded 0.49 g of crude material that was purified by RPLC (silica gel, 5% EtOAc/hex) to give 59% (0.2506 g) of 3-(1-methylpyrrolidin-2-yl)-4-trimethylsilanyl-4H-pyridine-1-carboxylic acid dimethylamide iii as a clear oil. IR (thin film, neat, NaCl): 3363, 2924, 2348, 1657, 1449, 1377 cm−1; 1H NMR (300 MHz, CDCl3) δ 6.65 (d, 1H, J=6.9 Hz), 6.35 (s 1H), 4.83-4.78 (m, 1 H), 3.14-3.09 (m, 1 H), 2.88 (s, 6 H), 2.80-1.25 (m, 13 H), 0.085 (s, 6 H); 13C NMR (100 MHz, CDCl3): δ 149.29, 147.15, 128.04, 124.49, 120.09, 106.29, 68.23, 57.35, 41.47, 38.53, 33.04, 30.34, 29.91, 22.37, 0.63, −2.00. HRMS Calcd for C16H29N3OSi: 308.2157 [M+H]+. Found: 308.2157 [M+H]+. [α]25D −15.17 (CH2Cl2, c=0.145).

Workup

  1. extractionThe aqueous phase was extracted with CH2Cl2 (5 times)
  2. washThe combined organic layers were washed with water and brine
  3. dry with materialdried over MgSO4
  4. customEvaporation of the solvent under reduced pressure
  5. customafforded 0.49 g of crude material that
  6. customwas purified by RPLC (silica gel, 5% EtOAc/hex)

Sources & evidence

ORD record
ord-ccfe546f51b947b1857ca6bc816d693f
Source dataset
uspto-grants-2009_06
Patent number
US07553968B2

Reaction notes

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