Imidazole → HCID 46836574, compound

HRID 1518354Notes

Reaction equation

HRID 1518354 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[S:24][C:25]([CH2:33][CH2:34][CH2:35]I)=[C:26]([C:28]([O:30]CC)=[O:29])[N:27]=1)[CH2:19][CH2:18]2)=[O:12].[NH:37]1[CH:41]=[CH:40][N:39]=[CH:38]1.[C:42]1(O)C=CC=CC=1>>[N:37]1([CH2:42][CH2:35][CH2:34][CH2:33][C:25]2[S:24][C:23]([N:20]3[CH2:19][CH2:18][C:17]4[C:22](=[C:13]([C:11](=[O:12])[NH:10][C:2]5[S:1][C:5]6[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=6[N:3]=5)[CH:14]=[CH:15][CH:16]=4)[CH2:21]3)=[N:27][C:26]=2[C:28]([OH:30])=[O:29])[CH:41]=[CH:40][N:39]=[CH:38]1

Participants

4

Reactant 3

HCID 795ImidazoleHCID 996PhenolHCID 59447467ethyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-iodopropyl)thiazole-4-carboxylate

Product 1

HCID 46836574HCID 46836574, compound

Procedure

The title compound 72 was prepared by substituting compound 42C for compound 2C and imidazole for phenol in step 4 of Example 2. The alkylation intermediate was not isolated prior to ester hydrolysis. After precipitation of the desired product, the solid was purified by HPLC (Preparative reverse phase HPLC was performed on an automated Gilson HPLC system, using a SymmetryPrep Shield RP18 prep cartridge, 250 mm×21.20 mm i.d., 10 um, and a flow rate of 25 mL/min; λ=214, 245 nm; mobile phase A, 0.1% TFA in H2O; mobile phase B, CH3CN; linear gradient 20-90% of B in 40 min) to provide the title compound in 34% yield: 1H NMR (300 MHz, DMSO-d6) δ ppm 12.91 (1H, s), 12.55 (1H, s), 9.06 (1H, s), 8.04 (1H, d), 7.77 (2H, m), 7.66 (2H, m), 7.43 (4H, m), 4.19 (2H, t), 3.73 (2H, t), 3.05 (4H, m), 1.83 (2H, m), 1.53 (2H, m). MS (ESI(+)) m/e 559 (M+H).

Workup

  1. customThe title compound 72 was prepared
  2. customThe alkylation intermediate was not isolated
  3. customAfter precipitation of the desired product
  4. customthe solid was purified by HPLC (Preparative reverse phase HPLC

Sources & evidence

ORD record
ord-85ee0f736bbc48fc93424c6a55c38aaf
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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