Sodium Hydroxide → (2-Methyl-4,5-dihydro-thiazolo[4,5-h]quinazolin-8-yl)-(4-morpholin-4-yl-phenyl)-amine

HRID 2102786Notes

Reaction equation

HRID 2102786 reaction equation
[CH3:1][C:2]1[S:3][C:4]2[C:10](=O)[C:9](=[CH:12]N3CCOCC3)[CH2:8][CH2:7][C:5]=2[N:6]=1.[N+]([O-])(O)=O.[N:23]1([C:29]2[CH:34]=[CH:33][C:32]([NH:35][C:36]([NH2:38])=[NH:37])=[CH:31][CH:30]=2)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.[OH-].[Na+]>COCCO>[CH3:1][C:2]1[S:3][C:4]2[C:10]3[N:38]=[C:36]([NH:35][C:32]4[CH:31]=[CH:30][C:29]([N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)=[CH:34][CH:33]=4)[N:37]=[CH:12][C:9]=3[CH2:8][CH2:7][C:5]=2[N:6]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 684158522-Methyl-6-morpholin-4-ylmethylene-5,6-dihydro-4H-benzothiazol-7-oneHCID 178512568N-(4-morpholin-4-yl-phenyl)-guanidine nitrate

Product 1

HCID 11199830(2-Methyl-4,5-dihydro-thiazolo[4,5-h]quinazolin-8-yl)-(4-morpholin-4-yl-phenyl)-amineYield 21%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Procedure

A mixture of 2-methyl-6-morpholin-4-ylmethylene-5,6-dihydro-4H-benzothiazol-7-one (200 mg, 7.6 mmol), N-(4-morpholin-4-yl-phenyl)-guanidine nitrate (215 mg, 7.6 mmol), NaOH (30 mg, 7.6 mmol), and 2-methoxyethanol (2 mL) was heated under reflux for 20 h. The reaction mixture was concentrated under vacuum. Flash column chromatography (5% MeOH:CH2Cl2), followed by crystallisation from EtOAc gave the pure title product as dark orange crystals (60 mg, 21%): mp 236-237° C. Anal. RP-HPLC: tR 13.4 min (0-60% MeCN, purity 100%). 1H-NMR (DMSO-d6): δ 9.26 (s, 1H, NH), 8.20 (s, 1H, Py-H), 7.58 (d, 2H, J 9.2, Ph-H), 6.84 (d, 2H, J 9.2, Ph-H), 3.70 (t, 4H, J 4.8, 2×CH2), 2.99 (t, 4H, J 4.8, 2×CH2), 2.90 (m, 4H, CH2—CH2), 2.66 (s, 3H, CH3).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 20 h
  3. concentrationThe reaction mixture was concentrated under vacuum
  4. customFlash column chromatography (5% MeOH:CH2Cl2), followed by crystallisation from EtOAc

Sources & evidence

ORD record
ord-21dae86f54a04478b0bcc474265311dc
Source dataset
uspto-grants-2009_08
Patent number
US07576091B2

Reaction notes

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