Sodium Hydroxide → HCID 18516874, compound

HRID 1370071Notes

Reaction equation

HRID 1370071 reaction equation
[N+]([O-])([O-])=O.[NH:5]1[C:13]2[C:8](=[CH:9][C:10]([NH:14][C:15]([NH2:17])=[NH2+:16])=[CH:11][CH:12]=2)[CH:7]=[N:6]1.[C:18]([O:22][C:23]([NH:25][C:26]([C:29]1[CH:34]=[CH:33][C:32]([C:35](=O)[C:36]([C:41]#N)=[CH:37][N:38](C)C)=[CH:31][CH:30]=1)([CH3:28])[CH3:27])=[O:24])([CH3:21])([CH3:20])[CH3:19].[OH-].[Na+]>CC(O)C>[C:18]([O:22][C:23]([NH:25][C:26]([C:29]1[CH:34]=[CH:33][C:32]([C:35]2[C:36]([C:37]#[N:38])=[CH:41][N:17]=[C:15]([NH:14][C:10]3[CH:9]=[C:8]4[C:13](=[CH:12][CH:11]=3)[NH:5][N:6]=[CH:7]4)[N:16]=2)=[CH:31][CH:30]=1)([CH3:28])[CH3:27])=[O:24])([CH3:20])([CH3:19])[CH3:21]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 54158929HCID 54158929, compoundHCID 178512435HCID 178512435, compound

Product 1

HCID 18516874HCID 18516874, compoundYield 90.5%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of indazol-5-ylguanidinium nitrate (524 mg, 2.2 mmol), 1-[4-(1-tert-butoxycarbonylamino-1-methylethyl)phenyl]-2-cyano-3-dimethylaminopropen-1-one (714 mg, 2.0 mmol) and powdered sodium hydroxide (96 mg, 2.4 mmol) in propan-2-ol (30 ml) was heated at reflux for 6 h. The reaction was concentrated in vacuo and the residue purified by column chromatography (silica, 60% ethyl acetate in hexane, loading the crude material in dichloromethane) to give 4-[4-(1-tert-butoxycarbonylamino-1-methylethyl)phenyl]-5-cyano-N-(indazol-5-yl)-pyrimidine-2-amine as a yellow solid (850 mg). δH (CDCl3) 8.69 (1H, s), 8.18 (1H, s), 8.11 (1H, s), 8.05 (2H, d, J 8.4 Hz), 7.93 (1H, bs), 7.57 (2H, d, J 8.4 Hz), 7.50 (2H, m), 5.10 (1H, bs), 1.66 (6H, s), 1.40 (9H, bs). MS (ESI) 492 (MNa+, 61%), 470 (MH+, 100%), 414 (19%). This product was dissolved in a mixture of TFA acid (20 ml) and CH2Cl2 (20 ml) and was stirred for 30 mins at room temperature before concentrating the reaction in vacuo. The residue was dissolved in 10% MeOH in CH2Cl2 (200 ml) and the organic phase washed with sat. Na2CO3 (aq) (50 ml), dried (MgSO4) and concentrated in vacuo to give the title compound as a bright yellow solid (541 mg) m.p. 267-271° (dec.). δH (d6DMSO) 13.03 (1H, bs), 10.46 (1H, s), 8.91 (1H, s), 8.16 (1H, s), 8.04 (1H, s), 7.94 (2H, d, J 8.4 Hz), 7.74 (2H, d, J 8.4 Hz), 7.61 (1H, m), 7.52 (1H, d, J 8.9 Hz), 3.44 (2H, bs), 1.48 (6H, s). MS (ESI) 392 (MNa+, 11%), 370 (MH+, 23%), 353 (100%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 6 h
  3. concentrationThe reaction was concentrated in vacuo
  4. customthe residue purified by column chromatography (silica, 60% ethyl acetate in hexane

Sources & evidence

ORD record
ord-277cc1a43e7b4cd59f736a58def3cb54
Source dataset
uspto-grants-2003_06
Patent number
US06579983B1

Reaction notes

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