Triethylamine → N-(cyanomethyl)-4-({[4-(methylsulfanyl)phenyl]sulfanyl}-methyl)bicyclo[4.1.0]heptane-3-carboxamide

HRID 2222909Notes

Reaction equation

HRID 2222909 reaction equation
Cl.[NH2:2][CH2:3][C:4]#[N:5].F[P-](F)(F)(F)(F)F.N1([PH+](N2CCCC2)N2CCCC2)CCCC1.[CH3:29][S:30][C:31]1[CH:36]=[CH:35][C:34]([S:37][CH2:38][CH:39]2[CH2:45][CH:44]3[CH:42]([CH2:43]3)[CH2:41][CH:40]2[C:46](O)=[O:47])=[CH:33][CH:32]=1.C(N(CC)CC)C>CN(C)C=O>[C:4]([CH2:3][NH:2][C:46]([CH:40]1[CH:39]([CH2:38][S:37][C:34]2[CH:35]=[CH:36][C:31]([S:30][CH3:29])=[CH:32][CH:33]=2)[CH2:45][CH:44]2[CH:42]([CH2:43]2)[CH2:41]1)=[O:47])#[N:5]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11491918Aminoacetonitrile hydrochlorideHCID 22226026Tripyrrolidinophosphonium hexafluorophosphateHCID 865961294-({[4-(Methylsulfanyl)phenyl]sulfanyl}-methyl)bicyclo[4.1.0]heptane-3-carboxylic acid

Product 1

HCID 59711774N-(cyanomethyl)-4-({[4-(methylsulfanyl)phenyl]sulfanyl}-methyl)bicyclo[4.1.0]heptane-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of aminoacetonitrile hydrochloride (153 mg, 1.65 mmol) and benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP) (800 mg, 1.54 mmol) was added 1S/R,3R/S,4R/S,6R/S)-4-({[4-(methylsulfanyl)phenyl]sulfanyl}methyl)bicyclo[4.1.0]-heptane-3-carboxylic acid and dimethylformamide (4 mL). After adding triethylamine (0.52 mL, 3.7 mmol) the reaction mixture was stirred at ambient temperature for 4 h. The reaction mixture was partitioned between water and ethyl acetate. The product was extracted into ethyl acetate and the combined organic phases were washed with saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate. The solvents were removed and the residue was chromatographed on a silica gel with methanol:dichloromethane (1.5:98.5) as eluent to give crude product which was purified in 1.4 mg portions by preparative RP HPLC (Waters, RCM, C18, μBondapak, 1×24 mm) by gradient elution with acetonitrile:water (containing 25 mM ammonium acetate)/30:70 to 50:50, 6.0 mL/min flowrate, UV detector set at 300 nM to give the title compound as a colorless solid. 1H NMR (500 MHz, acetone-d6): δ=7.83 (1H, br s), 7.28 (2H, d), 7.19 (2H, d), 4.20 (2H, m), 3.12 (1H, dd), 2.62 (1H, dd), 2.46 (3H, s), 2.26 (1H, m), 2.21 (1H, m), 2.10 (1H, m), 1.67 (1H, m), 1.58 (1H, m), 1.52 (1H, m), 0.99 (1H, m), 0.90 (1H, m), 0.57 (1H, m), −0.06 (1H, m). MS [ESI, (M−H)] m/z=345.2 amu.

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. extractionThe product was extracted into ethyl acetate
  3. washthe combined organic phases were washed with saturated sodium chloride aqueous solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvents were removed
  6. customthe residue was chromatographed on a silica gel with methanol:dichloromethane (1.5:98.5) as eluent
  7. customto give crude product which
  8. customwas purified in 1.4 mg portions by preparative RP HPLC (Waters, RCM, C18, μBondapak, 1×24 mm) by gradient elution with acetonitrile

Sources & evidence

ORD record
ord-2f4d8816fd2b4cd5b1b523ee1339a3a0
Source dataset
uspto-grants-2008_05
Patent number
US07371747B2

Reaction notes

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