Methanol → HCID 86689192, compound

HRID 589783Notes

Reaction equation

HRID 589783 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]2[S:11][C:10]([S:12]([NH:15][C:16]3[CH:17]=[C:18]([C:22]4[N:23]=[N:24][N:25]([CH2:27][C:28]([OH:30])=[O:29])[N:26]=4)[CH:19]=[CH:20][CH:21]=3)(=[O:14])=[O:13])=[C:9]([CH3:31])[C:8]=2[CH:32]=1)([CH3:3])[CH3:2].[C:33](N1C=CN=C1)(N1C=CN=C1)=O.N1C=CC=CC=1.CO.C(O)(C(F)(F)F)=O>CC#N.CS(C)=O.CO.O>[CH3:31][C:9]1[C:8]2[CH:32]=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:5]=[CH:6][C:7]=2[S:11][C:10]=1[S:12]([NH:15][C:16]1[CH:17]=[C:18]([C:22]2[N:23]=[N:24][N:25]([CH2:27][C:28]([O:30][CH3:33])=[O:29])[N:26]=2)[CH:19]=[CH:20][CH:21]=1)(=[O:13])=[O:14]

Participants

8

Reactant 5

HCID 887MethanolHCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 56942938HCID 56942938, compound

Product 1

HCID 86689192HCID 86689192, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 86689193HCID 86689193, compoundSolvent

Procedure

A reaction mixture containing [5-(3-{[(5-isopropyl-3-methyl-1-benzothien-2-yl)sulfonyl]-amino}phenyl)-2H-tetrazol-2-yl]acetic acid (5.7 mg, 0.012 mmol) (Example 12), 1,1′-carbonyldiimidazole (4.0 mg, 0.025 mmol) and pyridine (5.0 μL, 0.062 mmol) in MeCN (0.60 mL) was stirred at room temperature for 25 min. MeOH (50 μL, 1.23 mmol) was added. The reaction mixture was stirred at room temperature over night, and then diluted with DMSO/MeOH/water. TFA was added and the crude product was purified by reversed phase chromatography (ACE C8, 5 μm, 21×50 mm, flow 25 ml/min, 0.1% TFA in water/MeCN over 6 minutes). The title compound was obtained in 72% yield (4.2 mg). 1H NMR (500 MHz, CDCl3) δ ppm 1.28 (d, J=6.92 Hz, 6 H) 2.53 (s, 3 H) 3.02 (spt, J=6.92 Hz, 1 H) 3.82 (s, 3 H) 5.44 (s, 2 H) 6.92 (s, 1 H) 7.35 (ddd, J=8.11, 2.16, 1.28 Hz, 1 H) 7.35-7.38 (m, 1 H) 7.39 (dd, J=8.11, 7.50 Hz, 1 H) 7.53-7.55 (m, 1 H) 7.70 (d, J=8.42 Hz, 1 H) 7.90 (dd, J=2.16, 1.50 Hz, 1 H) 7.93 (ddd, J=7.50, 1.50, 1.28 Hz, 1 H). MS (ESI+) m/z 486 [M+H]+.

Workup

  1. stirringThe reaction mixture was stirred at room temperature over night
  2. customthe crude product was purified by reversed phase chromatography (ACE C8, 5 μm, 21×50 mm, flow 25 ml/min, 0.1% TFA in water/MeCN over 6 minutes)

Sources & evidence

ORD record
ord-ddf25d0fa270447086f4fa441bef34e7
Source dataset
uspto-grants-2016_01
Patent number
US09233946B2

Reaction notes

Loading…