Furfurylamine → HCID 86598176, compound

HRID 458468Notes

Reaction equation

HRID 458468 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:18]([CH2:19][C:20]2[CH:24]=[CH:23][S:22][CH:21]=2)=[N:17][C:9]2[C@H:10]3[N:14]([C:15](=[O:16])[C:8]=2[C:7]=1[C:25]1[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=1)[CH2:13][CH2:12][CH2:11]3)=[O:5])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH:55]1[CH:59]=[C:58]([CH2:60][NH2:61])[O:57][CH:56]=1>C(Cl)Cl.CCOCC>[O:57]1[CH:56]=[CH:55][CH:59]=[C:58]1[CH2:60][NH:61][C:29]([C:28]1[CH:32]=[CH:33][C:25]([C:7]2[C:8]3[C:15](=[O:16])[N:14]4[C@H:10]([C:9]=3[N:17]=[C:18]([CH2:19][C:20]3[CH:24]=[CH:23][S:22][CH:21]=3)[C:6]=2[C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:11][CH2:12][CH2:13]4)=[CH:26][CH:27]=1)=[O:30]

Participants

7

Reactant 4

HCID 3438FurfurylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 69742608HCID 69742608, compound

Product 1

HCID 86598176HCID 86598176, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred solution of 28 mg (0.060 mmol) of 4-[(9aS)-3-(ethoxycarbonyl)-5-oxo-2-(3-thienylmethyl)-7,8,9,9a-tetrahydro-5H-pyrido[2,3-α]pyrrolizin-4-yl]benzoic acid, 14 mg (1.2 equiv, 0.072 mmol) of EDCI and 10 mg (1.2 equiv., 0.072 mmol) of HOBT in 1 mL of DCM was treated with 13 mg (2.2 equiv., 0.133 mmol) of 2-furfurylamine. The resulting solution was stirred at room temperature for 3 h. The reaction mixture was then poured into Et2O (10 mL) and extracted with H2O (1×10 mL) and NaHCO3 (1×10 mL). The organic layer was separated, dried (MgSO4), filtered to remove solids, and concentrated in vacuo. The resulting crude material was purified by silica gel chromatography on an Elution Solutions medium pressure chromatography system using a gradient elution of hexanes/EtOAc 1:1 to 1:4 to afford a clear golden oil. The oil was then triturated with Et2O to afford 22 mg (68%) the title compound as a light yellow solid: 1H NMR (CDCl3, 400 MHz) δ 7.78 (d, 2H, J=7.9), 7.40 (d, 2H, J=7.9), 7.35 (s, 1H), 7.19 (m, 1H), 7.02 (s, 1H), 6.97 (d, 1H, J=4.8), 6.47 (m, 1H), 6.29 (d, 2H, J=15.4), 4.70 (dd, 1H, J=6.3, 10.2), 4.61 (d, 2H, J=5.4), 4.33 (AB quartet, 2H, J=14.5, 41.7), 3.86 (q, 2H, J=6.9), 3.65 (m, 1H), 2.47 (m, 1H), 2.30 (m, 2H), 1.41 (m, 1H), 1.22 (m, 2H), 1.18 (t, 3H, J=6.9); low resolution MS (ES+) m/e 543, (MH+1), 542 (MH+); TLC (hexanes/EtOAc (1:5)): Rf=0.25; HPLC (Dynamax RP-18, 4.6 mm×25 cm; 50–100% CH3CN/H2O with 0.1% TFA; 25 minutes; 1 mL/min): tR=7.73 min, 97% purity; Anal. (C30H27N3O5S) Calc. C, 66.53; H, 5.02; N, 7.76. Found C, 66.26; H, 4.87; N, 7.96.

Workup

  1. extractionextracted with H2O (1×10 mL) and NaHCO3 (1×10 mL)
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customto remove solids
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude material was purified by silica gel chromatography on an Elution Solutions medium pressure chromatography system
  8. washa gradient elution of hexanes/EtOAc 1:1 to 1:4
  9. customto afford a clear golden oil
  10. customThe oil was then triturated with Et2O

Sources & evidence

ORD record
ord-50b544fe79fc4e29945c8afebff8b9f9
Source dataset
uspto-grants-2007_03
Patent number
US07189851B2

Reaction notes

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