Hydrochloric Acid → 2-tert-Butyl-5-(3-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)-2-methylphenyl)-4H-pyrrolo[3,4-d]thiazol-6(5H)-one

HRID 872182Notes

Reaction equation

HRID 872182 reaction equation
Cl.[C:2]([C:6]1[S:7][C:8]2[C:13](=[O:14])[N:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]4[CH:26]=[C:25]([NH:27][C:28]5[CH:32]=[C:31]([CH3:33])[N:30]([CH3:34])[N:29]=5)[C:24](=[O:35])[N:23](COCC[Si](C)(C)C)[N:22]=4)[C:16]=3[CH3:44])[CH2:11][C:9]=2[N:10]=1)([CH3:5])([CH3:4])[CH3:3].C1(OC)C=CC=CC=1>CO>[C:2]([C:6]1[S:7][C:8]2[C:13](=[O:14])[N:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]4[CH:26]=[C:25]([NH:27][C:28]5[CH:32]=[C:31]([CH3:33])[N:30]([CH3:34])[N:29]=5)[C:24](=[O:35])[NH:23][N:22]=4)[C:16]=3[CH3:44])[CH2:11][C:9]=2[N:10]=1)([CH3:5])([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 7519AnisoleHCID 666135272-tert-butyl-5-(3-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-1,6-dihydropyridazin-3-yl)-2-methylphenyl)-4H-pyrrolo[3,4-d]thiazol-6(5H)-one

Product 1

HCID 569292322-tert-Butyl-5-(3-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)-2-methylphenyl)-4H-pyrrolo[3,4-d]thiazol-6(5H)-oneYield 30%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Hydrogen chloride gas was bubbled into 2-tert-butyl-5-(3-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-1,6-dihydropyridazin-3-yl)-2-methylphenyl)-4H-pyrrolo[3,4-d]thiazol-6(5H)-one 110c (186 mg, 0.30 mmol) and anisole (0.163 mL, 1.50 mmol) in methanol (20 mL) at 0° C. for 5 min. The resulting mixture was allowed to warm to room temperature and continue stirring for 16 h. The reaction mixture was concentrated. The residue was purified by reverse phase HPLC: C-18 column eluted with 20 to 60% Acetronitrile in water with 1% ammonium hydroxide over 14 min to afford 2-tert-butyl-5-(3-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)-2-methylphenyl)-4H-pyrrolo[3,4-d]thiazol-6(5H)-one 110 (40 mg, 30%). M+1 490.1. 1H NMR (400 MHz, DMSO) δ 12.95 (s, 1H), 9.09 (s, 1H), 7.77 (s, 1H), 7.50 (dd, J=5.6, 3.6, 1H), 7.41-7.32 (m, 2H), 5.97 (s, 1H), 4.97 (s, 2H), 3.62 (s, 3H), 2.17 (d, J=19.6, 6H), 1.47 (s, 9H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customThe residue was purified by reverse phase HPLC
  3. washC-18 column eluted with 20 to 60% Acetronitrile in water with 1% ammonium hydroxide over 14 min

Sources & evidence

ORD record
ord-9bbac8eed6db4dd9ad6a534b1cd2f3db
Source dataset
uspto-grants-2015_03
Patent number
US08975260B2

Reaction notes

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