1,1'-Carbonyldiimidazole → HCID 71062260, compound

HRID 528933Notes

Reaction equation

HRID 528933 reaction equation
[Cl:1][C:2]1[C:3]([C:45](=[O:55])[N:46]([CH2:51][CH2:52][CH2:53][CH3:54])[CH2:47][CH2:48][CH2:49][CH3:50])=[N:4][N:5]([C:11]2[CH:16]=[CH:15][C:14]([C:17](=[O:32])[NH:18][S:19]([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)(=[O:21])=[O:20])=[CH:13][C:12]=2[C:33]([N:35]2[CH2:44][CH2:43][C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH2:36]2)=[O:34])[C:6]=1[CH2:7][C:8](O)=[O:9].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:68]1([S:71]([NH2:74])(=[O:73])=[O:72])[CH2:70][CH2:69]1.C1CCN2C(=NCCC2)CC1>C1COCC1.CCOC(C)=O>[CH2:51]([N:46]([CH2:47][CH2:48][CH2:49][CH3:50])[C:45]([C:3]1[C:2]([Cl:1])=[C:6]([CH2:7][C:8]([NH:74][S:71]([CH:68]2[CH2:70][CH2:69]2)(=[O:73])=[O:72])=[O:9])[N:5]([C:11]2[CH:16]=[CH:15][C:14]([C:17](=[O:32])[NH:18][S:19]([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)(=[O:21])=[O:20])=[CH:13][C:12]=2[C:33]([N:35]2[CH2:44][CH2:43][C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH2:36]2)=[O:34])[N:4]=1)=[O:55])[CH2:52][CH2:53][CH3:54]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 71062428HCID 71062428, compound

Product 1

HCID 71062260HCID 71062260, compoundYield 18.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(4-chloro-3-(dibutylcarbamoyl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazol-5-yl)acetic acid (Example 171, 24 mg, 0.031 mmol) in THF (625 μL) was added CDI (16 mg, 0.10 mmol). The resulting solution was heated at reflux for 30 min and then cooled to room temperature. Cyclopropanesulfonamide (14 mg, 0.12 mmol) was then added followed by DBU (24 μL, 0.16 mmol), and the resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was then diluted with EtOAc, washed with 1N aq. HCl solution (2×) and extracted with EtOAc (3×). The combined organic extracts were washed with sat. aq. NaCl solution, dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC to give the title compound (5 mg, 16%) as a white solid after lyophilization. 1H NMR (CD3OD, 2:1 mixture of amide rotamers) δ 8.74 (s, 1H), 8.16-7.96 (m, 6H), 7.81-7.64 (m, 3H), 7.28-7.05 (m, 3.5H), 6.91 (d, J=7.5 Hz, 0.5H), 4.71-4.33 (m, 1.5H), 4.12-2.55 (m, 11.5H), 1.53-0.84 (m, 15H), 0.76 (t, J=7.4 Hz, 2H), 0.67 (t, J=7.4 Hz, 1H); MS(ESI+) m/z 887.5 (M+H)+.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureat reflux for 30 min
  3. customthe resulting reaction mixture
  4. washwashed with 1N aq. HCl solution (2×)
  5. extractionextracted with EtOAc (3×)
  6. washThe combined organic extracts were washed with sat. aq. NaCl solution
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-4558ed796e954db5a85e632c4cb1610e
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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