Dimethylformamide → Ethyl 3-(2-isopropylphenyl)-5-(4-morpholinobutoxy)-1-(3-(naphthalen-1-yloxy)propyl)-1h-indole-2-carboxylate

HRID 533274Notes

Reaction equation

HRID 533274 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][CH2:19][CH2:20][O:21][C:22]1[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:25]=[CH:24][CH:23]=1)[C:13]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[C:12]2[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[CH:43]([CH3:45])[CH3:44])[C:2]1[CH:7]=CC=CC=1.ClCC[CH2:49][CH2:50]I.[C:52](=[O:55])([O-])[O-].[Cs+].[Cs+].[CH3:58][N:59](C)[CH:60]=O>>[CH:43]([C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=1[C:12]1[C:11]2[C:15](=[CH:16][CH:17]=[C:9]([O:8][CH2:1][CH2:2][CH2:7][CH2:58][N:59]3[CH2:50][CH2:49][O:55][CH2:52][CH2:60]3)[CH:10]=2)[N:14]([CH2:18][CH2:19][CH2:20][O:21][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:25]=[CH:24][CH:23]=2)[C:13]=1[C:32]([O:34][CH2:35][CH3:36])=[O:33])([CH3:45])[CH3:44]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 825271-Chloro-4-iodobutaneHCID 67316990Ethyl 5-(benzyloxy)-3-(2-isopropylphenyl)-1-(3-(naphthalen-1-yloxy)propyl)-1h-indole-2-carboxylate

Product 1

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

Conditions

Temperature
60 °C

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).

Workup

  1. filtrationThe inorganic salt was filtered off
  2. additionTo the N,N-dimethylformamide solution was added morpholine (0.2 ml)
  3. concentrationThe reaction mixture was concentrated
  4. customthe residue was purified by RPHPLC (mobile phase: 10%-100% acetonitrile in 0.1% TFA aqueous solution during 60 min) on a C18 column

Sources & evidence

ORD record
ord-ae603c082c254385a0c017f72f568a94
Source dataset
uspto-grants-2014_10
Patent number
US08853209B2

Reaction notes

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