Hydrochloric Acid → HCID 67969363, compound

HRID 2365421Notes

Reaction equation

HRID 2365421 reaction equation
[F:1][C:2]1[CH:39]=[CH:38][C:5]([CH2:6][CH2:7][N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[C:27]([CH3:29])([CH3:28])[N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24][C:19]=5[N:20]([CH3:23])[C:21]=4[CH:22]=3)[C:10](=[O:37])[CH2:9]2)=[CH:4][CH:3]=1.[ClH:40]>CO.CCOCC>[ClH:40].[ClH:40].[F:1][C:2]1[CH:39]=[CH:38][C:5]([CH2:6][CH2:7][N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[C:27]([CH3:28])([CH3:29])[NH:26][CH2:25][CH2:24][C:19]=5[N:20]([CH3:23])[C:21]=4[CH:22]=3)[C:10](=[O:37])[CH2:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 67986827HCID 67986827, compound

Product 1

HCID 67969363HCID 67969363, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

tert-Butyl 7-(4-(4-fluorophenethyl)-2-oxopiperazin-1-yl)-1,1,5-trimethyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (106 mg, 0.240 mmol) was dissolved in MeOH (5.00 mL), and 2 M HCl in Et2O (1.20 mL) was added. The reaction was allowed to proceed for 18 h. The mixture was concentrated, and the residue was partitioned between CH2Cl2 and saturated NaHCO3 solution. The organic phase was separated, and the aqueous phase was back extracted with CH2Cl2. The combined organic extracts were dried over Na2SO4, filtered and concentrated to dryness. Purification by preparative thin layer chromatography (silica gel, 90:9:1 CH2Cl2/MeOH/NH4OH) gave the free base of the title compound (19.0 mg) as a white solid. The free base was dissolved in MeOH (2.00 mL) and treated with 1.25 M HCl in MeOH (0.108 mL). The mixture was concentrated to provide the title compound (22.0 mg, 17%) as an off-white solid. Free Base: 1H NMR (500 MHz, CDCl3) δ 7.57 (d, J=8.5 Hz, 1H), 7.21-7.17 (m, 3H), 7.02-6.94 (m, 3H), 3.75 (t, J=5.0 Hz, 2H), 3.59 (s, 3H), 3.43 (s, 2H), 3.26 (t, J=5.5 Hz, 2H), 2.90 (t, J=5.5 Hz, 2H), 2.86-2.82 (m, 2H), 2.74-2.69 (m, 4H), 1.55 (s, 6H); HPLC (Method B) 97.0% (AUC), tR=10.7 min. HCl salt: 1H NMR (500 MHz, CD3OD) δ 7.69 (d, J=8.5 Hz, 1H), 7.45 (s, 1H), 7.39-7.35 (m, 2H), 7.12-7.06 (m, 3H), 4.20-4.04 (m, 4H), 3.71-3.65 (m, 7H), 3.45-3.44 (m, 2H), 3.17-3.14 (m, 4H), 1.85 (s, 6H); ESI MS m/z 435 [M+H]+; HPLC (Method B) 95.2% (AUC), tR=10.8 min.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between CH2Cl2 and saturated NaHCO3 solution
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was back extracted with CH2Cl2
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customPurification by preparative thin layer chromatography (silica gel, 90:9:1 CH2Cl2/MeOH/NH4OH)

Sources & evidence

ORD record
ord-7ce078d748f2409d9df0c838c1e0c8e7
Source dataset
uspto-grants-2014_04
Patent number
US08697700B2

Reaction notes

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