Water → [4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diazabenz[a]azulen-2-yl]-acetic acid

HRID 1056855Notes

Reaction equation

HRID 1056855 reaction equation
[Li+].[OH-].C([O:5][C:6](=[O:27])[CH2:7][C:8]1[N:21]=[C:20]([N:22]([CH:24]2[CH2:26][CH2:25]2)[CH3:23])[C:11]2[C:12]3[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]=3[S:19][C:10]=2[N:9]=1)C.O>C1COCC1.Cl>[CH:24]1([N:22]([CH3:23])[C:20]2[C:11]3[C:12]4[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]=4[S:19][C:10]=3[N:9]=[C:8]([CH2:7][C:6]([OH:27])=[O:5])[N:21]=2)[CH2:25][CH2:26]1

Participants

6

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 89719440[4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl]-acetic acid ethyl ester

Product 1

HCID 71667913[4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diazabenz[a]azulen-2-yl]-acetic acidYield 94%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

The LiOH (0.615 g, 0.0150 mol) was added to a solution of [4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diaza-benz[a]azulen-2-yl]-acetic acid ethyl ester (1.8 g, 0.0050 mol) in 20 ml of (5:1) THF:water, and the mixture was stirred for 18 h at ambient temperature. The solvent was reduced under vacuum and the residue was diluted with 50 ml dilute aqueous HCl. The mixture was extracted with dichloromethane (50 ml×3) and the combined organic phase was separated, dried over Na2SO4 and concentrated under vacuum. The crude was purified by chromatography on silica gel using 2% MeOH-DCM to give [4-(cyclopropyl-methyl-amino)-6,7,8,9-tetrahydro-5H-10-thia-1,3-diazabenz[a]azulen-2-yl]-acetic acid (1.5 g, 94%) as pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 15.52 (brs, 1H), 3.96 (s, 2H), 3.09 (s, 3H), 2.85-2.98 (m, 4H), 2.72-2.80 (m, 1H), 1.85-1.95 (m, 2H), 1.68-1.78 (m, 2H), 1.85-1.67 (m, 2H), 0.88-0.98 (m, 2H), 0.52-0.67 (m, 2H); LC-MS: [M+H]=332.2 m/z.

Workup

  1. extractionThe mixture was extracted with dichloromethane (50 ml×3)
  2. customthe combined organic phase was separated
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under vacuum
  5. customThe crude was purified by chromatography on silica gel using 2% MeOH-DCM

Sources & evidence

ORD record
ord-eae8a9b8e42e4c2698d630921ff89a15
Source dataset
uspto-grants-2016_07
Patent number
US09399647B2

Reaction notes

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