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 2178428Notes

Reaction equation

HRID 2178428 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-942f1b642dd24117bdb6b7c0161e3278
Source dataset
uspto-grants-2015_06
Patent number
US09067917B2

Reaction notes

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