Acetic Acid → HCID 67443036, compound

HRID 1400895Notes

Reaction equation

HRID 1400895 reaction equation
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH2:25][CH2:26][NH:27][CH2:28][CH:29]=5)[S:23][C:16]=34)=[C:10]([F:30])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.[CH3:31][C:32]([OH:34])=O.[C:35](O[BH-](OC(=O)C)OC(=O)C)(=O)[CH3:36].[Na+].CN(C=O)C>C(Cl)Cl.O.C1COCC1>[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH2:25][CH2:26][N:27]([CH2:35][CH2:36][CH2:31][CH2:32][OH:34])[CH2:28][CH:29]=5)[S:23][C:16]=34)=[C:10]([F:30])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 5049666Sodium triacetoxyborohydrideHCID 67441492HCID 67441492, compound

Product 1

HCID 67443036HCID 67443036, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of compound 271-A (80 mg, 0.188 mmol) and AcOH (12 μl, 0.207 mmol) in DCM (10 mL) was added 2,5,8,11-tetraoxamidecan-13-al (78 mg, 0.377 mmol, L. Gorini, et. al. SynLett., 2006, 948-950). After 30 min, sodium triacetoxyborohydride (120 mg, 0.565 mmol) was added and the reaction mixture was stirred at RT for 1 h. DMF (1 mL) and THF (2 mL) were added to the suspension that was stirred at RT for and additional 18 h. The reaction mixture was diluted with water and concentrated. The residue was purified by Biotage (SNAP 25 g cartridge; MeOH/DCM: 0/100 to 15/85 over 20 CV) to afford a material that upon trituration with MTBE afforded an unexpected compound 277 (30 mg, 0.06 mmol, 32% yield) as beige solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.78 (s, 1H), 8.44 (d, J=5.2 Hz, 1H), 7.71 (dd, J=2.4 and 13.6 Hz, 1H), 7.47 (s, 1H), 7.33 (t, J=9.2 Hz, 1H), 7.22-7.15 (m, 1H), 6.63 (d, J=2.0 Hz, 1H), 6.55 (d, J=5.2 Hz, 1H), 6.37 (s, 1H), 3.40 (t, J=6.4 Hz, 1H), 3.14-3.09 (m, 2H), 2.68-2.50 (m, 5H), 2.40 (t, J=6.4 Hz, 2H), 1.56-1.41 (m, 4H), 0.68-0.61 (m, 2H), 0.44-0.40 (m, 2H). MS (m/z): 497.2 (M+H).

Workup

  1. additionwas added 2,5,8,11-tetraoxamidecan-13-al (78 mg, 0.377 mmol, L. Gorini, et. al. SynLett., 2006, 948-950)
  2. stirringwas stirred at RT for and additional 18 h
  3. concentrationconcentrated
  4. customThe residue was purified by Biotage (SNAP 25 g cartridge; MeOH/DCM: 0/100 to 15/85 over 20 CV)
  5. customto afford a material that upon trituration with MTBE

Sources & evidence

ORD record
ord-eb5f0e7391314468bb4920a9837e5f39
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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