Tetrahydrofuran → HCID 86687238, compound

HRID 1402393Notes

Reaction equation

HRID 1402393 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:40])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:41]2[CH:42]=[C:43]([CH2:47][CH2:48][O:49]S(C)(=O)=O)[CH:44]=[CH:45][CH:46]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:54][N:55]1[CH2:61][CH2:60][CH2:59][NH:58][CH2:57][CH2:56]1.C1C[O:65]CC1>>[CH:48]([OH:49])=[O:65].[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C@@H:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@H:17]([O:24][C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:31]([N:34]5[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]5[CH3:40])=[N:32][N:33]=4)[CH:30]=3)[CH2:16][CH2:15]2)=[O:12])[N:7]([C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][CH2:48][N:58]3[CH2:59][CH2:60][CH2:61][N:55]([CH3:54])[CH2:56][CH2:57]3)[CH:42]=2)[N:6]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 2283491-MethylhomopiperazineHCID 86687227HCID 86687227, compound

Product 1

HCID 86687238HCID 86687238, compound

Procedure

A solution of Intermediate 131d (44.5 mg, 0.06 mmol) and N-methylhomopiperazine (34.3 mg, 0.300 mmol) in THF (1 mL) was stirred at 60° C. for 20 h in a sealed tube. The mixture was concentrated in vacuo and the residue purified by MDAP (Method 7) to give an off-white solid (22 mg). Prep HPLC (Gemini C18, 20-60% MeCN in water, 0.1% HCO2H, 20 min) and concentration of the desired fractions removed the MeCN. The aqueous was washed with DCM (30 mL), then basified with aq. NaOH solution (1M, 0.5 mL) and extracted with DCM (2×10 mL). The combined organics were passed through a hydrophobic frit, then HCO2H (0.01 mL) added and the mixture concentrated in vacuo to leave the title compound as a clear film that became a solid on standing (10.6 mg, 23%). LCMS (Method 5): Rt 3.19 min, m/z 759.7 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.91 (3H, d, J=6.3 Hz), 1.28 (9H, s), 1.48-1.55 (2H, m), 1.64-1.74 (4H, m), 1.77-1.96 (4H, m), 2.00-2.16 (2H, m), 2.29 (3H, s), 2.58-2.62 (4H, m), 2.69-2.80 (8H, m), 2.91 (1H, ddd, J=12.4, 9.3, 4.3 Hz), 3.16 (1H, dt, J=11.9, 4.3 Hz), 3.28-3.34 (1H, m), 4.82 (1H, td, J=9.0, 5.7 Hz), 5.52 (1H, t, J=4.3 Hz), 6.33 (1H, s), 7.09 (1H, d, J=8.6 Hz), 7.19 (1H, dd, J=9.8, 2.2 Hz), 7.24-7.42 (8H, m), 7.64 (1H, dd, J=9.8, 0.8 Hz), 7.69 (1H, dd, J=2.2, 0.9 Hz), 8.10 (1H, s), 8.19 (1.4H, s).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue purified by MDAP (Method 7)

Sources & evidence

ORD record
ord-3aa59ccc04f247b48accf44790437c1f
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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