2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → HCID 67220208, compound

HRID 1510833Notes

Reaction equation

HRID 1510833 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC1C=CC2C(=CC=CC=2)N1C(OCC)=O)C.[NH2:34][C:35]1[C:43]2[C:38](=[CH:39][C:40]([C:44]3[CH:49]=[CH:48][C:47]([C:50]4[NH:54][C:53]([C@@H:55]5[CH2:59][CH2:58][CH2:57][N:56]5[C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])=[N:52][CH:51]=4)=[CH:46][CH:45]=3)=[CH:41][CH:42]=2)[N:37]([C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])[N:36]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CO>[C:63]([O:62][C:60]([N:56]1[CH2:57][CH2:58][CH2:59][C@H:55]1[C:53]1[NH:54][C:50]([C:47]2[CH:48]=[CH:49][C:44]([C:40]3[CH:39]=[C:38]4[C:43]([C:35]([NH:34][C:13]([C@@H:9]5[CH2:10][CH2:11][CH2:12][N:8]5[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:15])=[N:36][N:37]4[C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])=[CH:42][CH:41]=3)=[CH:45][CH:46]=2)=[CH:51][N:52]=1)=[O:61])([CH3:66])([CH3:65])[CH3:64]

Participants

7

Reactant 4

HCID 278332-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline2×HCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-2×HCID 67220801HCID 67220801, compound

Product 1

HCID 67220208HCID 67220208, compoundYield 69.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (97.1 mg, 0.451 mmol) in CH2Cl2 (2 mL) was added ethyl 2-ethoxyquinoline-1(2H)-carboxylate (EEDQ, 181.2 mg, 0.733 mmol) followed by (S)-tert-butyl 3-amino-6-(4-(2-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)phenyl)-1H-indazole-1-carboxylate (209.7 mg, 0.385 mmol) after about 5 min. The reaction mixture as allowed to stir at room temperature for 12 h and the solution was treated with EEDQ (79 mg, 0.365 mmol) and stirred for 48 h. The solution was treated with (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (60 mg, 0.279 mmol). After stirring a further 12 h the mixture was treated with MeOH (4 mL) followed by iPr2NEt (0.1 mL) and allowed to stir for 2 h. The solvent was removed in vacuo and the residue was purified by prep HPLC (CH3CN—H2O—NH4OAc) to give the title compound (197.4 mg, 69%) as a light yellow glass. 1H NMR (400 MHz, DMSO-d6) δ 11.90-11.95 (m, 1H), 11.13-11.20 (m, 1H), 8.33 (s, 1H), 8.09 (d, J=8 Hz, 1H), 7.88 (app d, J=8 Hz, 2H), 7.65-7.78 (m, 3H), 7.55-7.58 (m, 1H), 4.75-4.87 (m, 2H), 4.36-4.43 (m, 1H), 4.06-4.12 (m, 1H), 3.51-3.59 (m, 1H), 3.42-3.47 (m, 1H), 3.35-3.37 (m, 2H, partially obscured by H2O signal), 2.12-2.32 (m, 2H), 1.79-2.01 (m, 4H), 1.66 (s, 9H), 1.40 (s, 9H), 1.32 and 1.15 (s, 9H, rotamers). LCMS: Anal. Calcd. for C40H51N7O7: 741; found: 742 (M+H)+.

Workup

  1. stirringstirred for 48 h
  2. stirringAfter stirring a further 12 h the mixture
  3. stirringto stir for 2 h
  4. customThe solvent was removed in vacuo
  5. customthe residue was purified by prep HPLC (CH3CN—H2O—NH4OAc)

Sources & evidence

ORD record
ord-f2e4d53637894f5fa65cee35870f6bd5
Source dataset
uspto-grants-2012_07
Patent number
US08211928B2

Reaction notes

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