1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86680512, compound

HRID 1184591Notes

Reaction equation

HRID 1184591 reaction equation
[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][NH:17][CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.Br[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][C:28]([OH:30])=O)=[CH:23][C:22]=1[C:31]([F:34])([F:33])[F:32].[CH2:35]([N:37]=C=NCCCN(C)C)C.O.OC1C2N=NNC=2C=CC=1.C(N(C(C)C)CC)(C)C.[Cu]C#N>ClCCl>[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][N:17]([C:28](=[O:30])[CH2:27][C:24]5[CH:25]=[CH:26][C:21]([C:35]#[N:37])=[C:22]([C:31]([F:34])([F:33])[F:32])[CH:23]=5)[CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 269863604-Bromo-3-(trifluoromethyl)benzeneacetic acidHCID 86680449(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]octahydropyrrolo[1,2-a]pyrazineHCID 178418546HCID 178418546, compoundHCID 178526939HCID 178526939, compound

Product 1

HCID 86680512HCID 86680512, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of the product from Example 54F (100 mg, 0.300 mmol), 2-(4-bromo-3-(trifluoromethyl)phenyl)acetic acid (127 mg, 0.450 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (115 mg, 0.600 mmol), hydroxybenzotriazole hydrate (92 mg, 0.600 mmol), and diisopropylethylamine (0.262 mL, 1.500 mmol) in dichloromethane (3.0 mL) was stirred at room temperature for 3 hours. The mixture was partitioned between water and ethyl acetate, and the organic extract was dried over Na2SO4. The mixture was filtered, concentrated and dried in vacuo, and the residue was dissolved in anhydrous N,N-dimethylformamide (2 mL). Copper(I) cyanide (0.11 g, 1.228 mmol) was added, and the resulting mixture was stirred at 130° C. under N2 for 2 days. The mixture was allowed to cool to room temperature and was partitioned between water (10 mL) and ethyl acetate (4×10 mL). The organic layers were combined and dried over Na2SO4, filtered and concentrated in vacuo to give a crude product that was purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane. The title compound was obtained as a colorless solid (45 mg, 32%). 1H NMR (300 MHz, CDCl3) δ ppm 0.84-1.05 (m, 4 H), 1.80-2.07 (m, 3 H), 2.13-2.53 (m, 3.5 H), 2.73-3.10 (m, 2 H), 3.22-3.35 (m, 0.5 H), 3.63-3.99 (m, 4 H), 4.53-4.80 (m, J=38.32, 12.55 Hz, 1 H), 5.31-5.42 (m, 1 H), 7.56 (d, J=7.80 Hz, 1 H), 7.67 (s, 1 H), 7.80 (d, J=8.14 Hz, 1 H), 7.92-7.95 (m, 1 H), 8.00-8.05 (m, J=1.36 Hz, 1 H); MS (ESI) m/z 472 (M+H)+.

Workup

  1. customThe mixture was partitioned between water and ethyl acetate
  2. extractionthe organic extract
  3. dry with materialwas dried over Na2SO4
  4. filtrationThe mixture was filtered
  5. concentrationconcentrated
  6. customdried in vacuo
  7. dissolutionthe residue was dissolved in anhydrous N,N-dimethylformamide (2 mL)
  8. stirringthe resulting mixture was stirred at 130° C. under N2 for 2 days
  9. temperatureto cool to room temperature
  10. customwas partitioned between water (10 mL) and ethyl acetate (4×10 mL)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto give a crude product that
  15. customwas purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-5521ad8c6bb7446bbd391bbc32639f51
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

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