Dicyclohexylcarbodiimide → 6-fluoro-N-{[(2S)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}-2,3,4,9-tetrahydro-1H-carbazole-2-carboxamide

HRID 1593605Notes

Reaction equation

HRID 1593605 reaction equation
Cl.[CH3:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]3[O:16][CH2:15][C@H:14]([CH2:17][NH2:18])[O:13][C:9]3=2)[N:4]=1.[F:19][C:20]1[CH:21]=[C:22]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28]1[CH2:27][CH:26]([C:33](O)=[O:34])[CH2:25][CH2:24][C:23]2=1.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>O1CCCC1.C(N(CC)CC)C>[F:19][C:20]1[CH:21]=[C:22]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28]1[CH2:27][CH:26]([C:33]([NH:18][CH2:17][C@@H:14]3[O:13][C:9]4=[C:10]5[C:5](=[CH:6][CH:7]=[C:8]4[O:16][CH2:15]3)[N:4]=[C:3]([CH3:2])[CH:12]=[CH:11]5)=[O:34])[CH2:25][CH2:24][C:23]2=1

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 214527086-Fluoro-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylic acidHCID 69469039[(2S)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methylamine hydrochloride

Product 1

HCID 866076466-fluoro-N-{[(2S)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl}-2,3,4,9-tetrahydro-1H-carbazole-2-carboxamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

[(2S)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methylamine hydrochloride (360 mg, 1.35 mmol) and compound I were suspended in anhydrous tetrahydrofuran (THF) containing triethylamine (1.8 mL) and HOBT (54 mg) with stirring for 15 min. The coupling reagent, DCC (300 mg) was added and stirring was continued overnight. The reaction mixture was filtered and the filtrate was diluted with water and extracted with ether. The ether layers were combined, dried (MgSO4), and evaporated under reduced pressure to give a residue which was purified by flash chromatography on silica gel eluting with 1-2% methanol in methylene chloride to give the intermediate II (240 mg) as a white solid. mp 262-267° C.; MS (ES) m/z 444.3.

Workup

  1. stirringstirring
  2. waitwas continued overnight
  3. filtrationThe reaction mixture was filtered
  4. additionthe filtrate was diluted with water
  5. extractionextracted with ether
  6. dry with materialdried (MgSO4)
  7. customevaporated under reduced pressure
  8. customto give a residue which
  9. customwas purified by flash chromatography on silica gel eluting with 1-2% methanol in methylene chloride

Sources & evidence

ORD record
ord-b2606a0f859249e08d0688ad35c716a6
Source dataset
uspto-grants-2007_11
Patent number
US07297704B2

Reaction notes

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