Sodium Hydroxide → 3-(2-Isopropylphenyl)-5-(4-morpholin-4-ylbutoxy)-1-(3-(1-naphthyloxy)propyl)-1h-indole-2-carboxylic acid

HRID 533275Notes

Reaction equation

HRID 533275 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH2:20][CH2:21][CH2:22][CH2:23][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:17]=2)[N:12]([CH2:30][CH2:31][CH2:32][O:33][C:34]2[C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH:37]=[CH:36][CH:35]=2)[C:11]=1[C:44]([O:46]CC)=[O:45])([CH3:3])[CH3:2].[OH-].[Na+]>O1CCCC1.CO>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:19][CH2:20][CH2:21][CH2:22][CH2:23][N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[CH:17]=2)[N:12]([CH2:30][CH2:31][CH2:32][O:33][C:34]2[C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH:37]=[CH:36][CH:35]=2)[C:11]=1[C:44]([OH:46])=[O:45])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 67315875Ethyl 3-(2-isopropylphenyl)-5-(4-morpholinobutoxy)-1-(3-(naphthalen-1-yloxy)propyl)-1h-indole-2-carboxylate

Product 1

HCID 673154993-(2-Isopropylphenyl)-5-(4-morpholin-4-ylbutoxy)-1-(3-(1-naphthyloxy)propyl)-1h-indole-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of EXAMPLE 149A (36 mg), 1-chloro-4-iodobutane (0.043 ml) and cesium carbonate (116 mg) in N,N-dimethylformamide (2 ml) was stirred at room temperature overnight. The inorganic salt was filtered off. To the N,N-dimethylformamide solution was added morpholine (0.2 ml) and the resulting mixture was heated at 60° C. for 5 hours. The reaction mixture was concentrated and the residue was purified by RPHPLC (mobile phase: 10%-100% acetonitrile in 0.1% TFA aqueous solution during 60 min) on a C18 column to give ethyl 3-(2-isopropylphenyl)-5-(4-morpholinobutoxy)-1-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylate. This ester was hydrolyzed with aqueous NaOH in a mixture of tetrahydrofuran and methanol to provide the title compound. 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ 9.52 (s, 1H), 8.20 (d, J=8.29 Hz, 1H), 7.87 (d, J=7.98 Hz, 1H), 7.59 (d, J=8.90 Hz, 1H), 7.43-7.57 (m, 3H), 7.30-7.43 (m, 3H), 7.14-7.23 (m, 1H), 7.06 (d, J=7.36 Hz, 1H), 6.89 (dd, J=9.05, 2.30 Hz, 1H), 6.85 (d, J=7.67 Hz, 1H), 6.43 (d, J=2.45 Hz, 1H), 4.88 (t, J=7.21 Hz, 2H), 4.15 (t, J=5.83 Hz, 2H), 3.89-4.03 (m, J=11.97 Hz, 2H), 3.75-3.89 (m, 2H), 3.55-3.70 (m, 2H), 3.07-3.17 (m, 2H), 3.02 (s, br, 2H), 2.61-2.78 (m, 2H), 2.23-2.45 (m, 2H), 1.60-1.85 (m, 4H).

Sources & evidence

ORD record
ord-4037c106b2f248d39fac602d75125679
Source dataset
uspto-grants-2014_10
Patent number
US08853209B2

Reaction notes

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