Triethylamine → HCID 86596145, compound

HRID 2222926Notes

Reaction equation

HRID 2222926 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH:10]2[CH2:16][CH2:15][CH:14]3[CH:12]([CH2:13]3)[CH:11]2[C:17]([OH:19])=O)=[CH:4][CH:3]=1.C1CN([P+](O[N:37]2N=[N:44][C:39]3C=CC=C[C:38]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.NCC#N.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[C:38]([CH2:39][NH:44][C:17]([CH:11]1[CH:10]([CH2:9][S:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:16][CH2:15][CH:14]2[CH:12]1[CH2:13]2)=[O:19])#[N:37]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 2724699PyBOPHCID 11491918Aminoacetonitrile hydrochlorideHCID 86596144HCID 86596144, compound

Product 1

HCID 86596145HCID 86596145, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To (1R/S,2R/S,3R/S,6S/R)-3-{[(4-fluorophenyl)sulfanyl]methyl}bicyclo[4.1.0]heptane-2-carboxylic acid (310 mg, 1.12 mmol), PyBOP (640 mg, 1.23 mmol), and aminoacetonitrile hydrochloride (228 mg, 2.46 mmol) was added dry dimethylformamide (10 mL) under an atmosphere of dry nitrogen followed by triethylamine (550 μL, 3.92 mmol) and the reaction mixture was stirred for 4.5 h at room temperature. The reaction mixture was poured into aqueous saturated sodium hydrogen carbonate, extracted with ether, and dried over anhydrous sodium sulfate. The solvent was concentrated in vacuo and the crude product was purified by flash chromatography over silica gel (ethyl acetate/hexanes, 4/6) to yield (1R/S,2R/S,3R/S,6S/R)-N-(cyanomethyl)-3-{[(4-fluorophenyl)sulfanyl]methyl}-bicyclo[4.1.0]heptane-2-carboxamide. 1H NMR (400 MHz, acetone-d6): δ=7.85 (1H, br s), 7.42-7.35 (2H, m), 7.11-7.05 (2H, m), 4.314.19 (2H, m), 2.98 (1H, dd), 2.83 (1H, m), 2.72 (1H, dd), 1.94 (1H, m), 1.85-1.75 (2H, m), 1.54 (1H, m), 1.27-1.16 (2H, m), 0.98 (1H, m), 0.63 (1H, dt). MS [ESI, (M−H)−] m/z=317.0 amu.

Workup

  1. extractionextracted with ether
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationThe solvent was concentrated in vacuo
  4. customthe crude product was purified by flash chromatography over silica gel (ethyl acetate/hexanes, 4/6)

Sources & evidence

ORD record
ord-34e79e241a4b42bbb8546d3f68bc0193
Source dataset
uspto-grants-2008_05
Patent number
US07371747B2

Reaction notes

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