Hydrochloric Acid → racemic cis-3-{1-[(1-Ethyl-1H-indazol-3-yl)methyl]-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl}-2,2-dimethylcyclopropanecarboxylic acid

HRID 1776721Notes

Reaction equation

HRID 1776721 reaction equation
[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][NH:13][C:14]2[C:15]([NH2:32])=[CH:16][C:17]([O:20][CH2:21][C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]=3)=[CH:18][CH:19]=2)=[N:4]1)[CH3:2].[CH3:33][C:34]1([CH3:42])[C@@H:39]2[C@H:35]1[C:36](=[O:41])[O:37][C:38]2=O.Cl>C(#N)C>[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][N:13]2[C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]4[CH:31]=[CH:30][C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[N:23]=4)=[CH:16][C:15]=3[N:32]=[C:38]2[C@@H:39]2[C@H:35]([C:36]([OH:41])=[O:37])[C:34]2([CH3:42])[CH3:33])=[N:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 12851675HCID 12851675, compoundHCID 131733024N1-((1-ethyl-1H-indazol-3-yl)methyl)-4-(quinolin-2-ylmethoxy)benzene-1,2-diamine

Product 1

HCID 90414636racemic cis-3-{1-[(1-Ethyl-1H-indazol-3-yl)methyl]-5-(quinolin-2-ylmethoxy)-1H-benzimidazol-2-yl}-2,2-dimethylcyclopropanecarboxylic acid

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a 25 mL round-bottomed flask was added N1-((1-ethyl-1H-indazol-3-yl)methyl)-4-(quinolin-2-ylmethoxy)benzene-1,2-diamine (37 mg, 0.09 mmol), cis-6,6-dimethyl-3-oxa-bicyclo[3.1.0]hexane-2,4-dione (12 mg, 0.09 mmol) and acetonitrile (0.8 mL). The solution was heated to 80° C. for 4 h. To this solution was added HCl (0.4 mL, 6 N) and the mixture heated to 90° C. for 15 h. The mixture was cooled to RT over 30 minutes. The resulting solids were filtered off and the liquid purified by reverse phase HPLC to afford the title compound. MS (ESI): mass calcd. for C33H31N5O3, 545.24; m/z found, 546.2 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 8.57 (d, J=8.5, 1H), 8.37 (d, J=8.7, 1H), 7.99 (d, J=8.2, 1H), 7.95-7.89 (m, 2H), 7.76-7.72 (m, 1H), 7.55 (d, J=9.1, 1H), 7.42-7.37 (m, 4H), 7.25-7.22 (m, 1H), 7.16-7.11 (m, 1H), 5.72 (s, 2H), 5.66 (s, 2H), 4.36 (q, J=7.3, 2H), 2.50 (s, 2H), 1.45 (t, J=7.3, 3H), 1.29 (s, 3H), 1.10 (s, 3H).

Workup

  1. temperaturethe mixture heated to 90° C. for 15 h
  2. temperatureThe mixture was cooled to RT over 30 minutes
  3. filtrationThe resulting solids were filtered off
  4. customthe liquid purified by reverse phase HPLC

Sources & evidence

ORD record
ord-e8cd6524b5574ffb993604345ffb2e3c
Source dataset
uspto-grants-2016_02
Patent number
US09265770B2

Reaction notes

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