Diisopropylethylamine → HCID 68656848, compound

HRID 930761Notes

Reaction equation

HRID 930761 reaction equation
Cl.[Cl:2][CH2:3][CH2:4][N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1.[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][N:21]([C:24]2[CH:32]=[C:31]3[C:27]([C:28]4[CH2:37][CH2:36][NH:35][CH2:34][C:29]=4[N:30]3[CH3:33])=[CH:26][CH:25]=2)[C:20](=[O:38])[CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(N(C(C)C)CC)(C)C>CCO>[ClH:2].[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][N:21]([C:24]2[CH:32]=[C:31]3[C:27]([C:28]4[CH2:37][CH2:36][N:35]([CH2:3][CH2:4][N:5]5[CH2:9][CH2:8][CH2:7][CH2:6]5)[CH2:34][C:29]=4[N:30]3[CH3:33])=[CH:26][CH:25]=2)[C:20](=[O:38])[CH:19]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 50908737HCID 50908737, compound

Product 1

HCID 68656848HCID 68656848, compoundYield 7.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
65 °C

Procedure

1-(2-Chloroethyl)pyrrolidine hydrochloride (50 mg, 0.29 mmol) was added to a solution of 4-(benzyloxy)-1-(9-methyl-2,3,4,9,-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridine-2(1H)-one (0.10 g, 0.27 mmol) and diisoproylethyl amine (0.14 mL) in EtOH (4 mL), and the resulting solution was heated at 65° C. for 2 h. The reaction mixture was concentrated to dryness under reduced pressure. Purification by flash column chromatography (40 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 hold 5 column volumes increased to 0:100 over 20 column volumes) followed by preparative TLC (Analtech, 20×20 cm, 1000 microns, uV 254, 80:18:2 CH2Cl2/MeOH/NH4OH) followed by preparative HPLC (Phenomenex Luna C18 (2), 250.0×21.2 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA) and filtration through SCX-2 column gave the title compound (10 mg, 7%) as a yellow solid: 1H NMR (500 MHz, CD3OD) δ 7.54 (d, J=7.5 Hz, 1H), 7.51 (d, J=8.5 Hz, 1H), 7.46-7.33 (m, 6H), 6.96 (dd, J=8.0, 1.5 Hz, 1H), 6.26 (dd, J=7.5, 2.5, Hz, 1H), 6.11 (d, J=3.0 Hz, 1H), 5.16 (s, 2H), 3.82 (s, 2H), 3.64 (s, 3H), 3.01-2.99 (m, 2H), 2.94-2.85 (m, 10H), 1.91-1.90 (m, 4H); HPLC (Method A) 95.1% (AUC), tR=13.8 min.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  2. customPurification
  3. temperatureby flash column chromatography (40 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 hold 5 column volumes increased to 0:100 over 20 column volumes)
  4. filtrationfollowed by preparative HPLC (Phenomenex Luna C18 (2), 250.0×21.2 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA) and filtration through SCX-2 column

Sources & evidence

ORD record
ord-23f4ff101d9640cfaf219845bafcc2da
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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