Hydrochloric Acid → 4-amino-1-((8-methyl-1-oxo-2-o-tolyl-1,2-dihydroisoquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid

HRID 1506099Notes

Reaction equation

HRID 1506099 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:13][C:14]3[N:15]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[CH3:32])[C:16](=[O:25])[C:17]4[C:22]([CH:23]=3)=[CH:21][CH:20]=[CH:19][C:18]=4[CH3:24])[N:9]=[C:10]([CH:11]=[O:12])[C:3]=12.[O-]Cl=O.[Na+].Cl.[NH2:38][C:39]1[N:44]=[CH:43][N:42]=[C:41]2[N:45]([CH2:51][C:52]3[N:53]([C:64]4[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=4[CH3:70])[C:54](=[O:63])[C:55]4[C:60]([CH:61]=3)=[CH:59][CH:58]=[CH:57][C:56]=4[CH3:62])[N:46]=[C:47]([C:48]([OH:50])=[O:49])[C:40]=12>CC(O)(C)C.O.CCC=CC>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:13][C:14]3[N:15]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[CH3:32])[C:16](=[O:25])[C:17]4[C:22]([CH:23]=3)=[CH:21][CH:20]=[CH:19][C:18]=4[CH3:24])[N:9]=[C:10]([C:11]([NH2:38])=[O:12])[C:3]=12.[NH2:38][C:39]1[N:44]=[CH:43][N:42]=[C:41]2[N:45]([CH2:51][C:52]3[N:53]([C:64]4[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=4[CH3:70])[C:54](=[O:63])[C:55]4[C:60]([CH:61]=3)=[CH:59][CH:58]=[CH:57][C:56]=4[CH3:62])[N:46]=[C:47]([C:48]([OH:50])=[O:49])[C:40]=12

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 23668197Sodium ChloriteHCID 580085994-amino-1-((8-methyl-1-oxo-2-o-tolyl-1,2-dihydroisoquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carbaldehyde2×HCID 580088444-amino-1-((8-methyl-1-oxo-2-o-tolyl-1,2-dihydroisoquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid

Product 2

HCID 580085964-amino-1-((8-methyl-1-oxo-2-o-tolyl-1,2-dihydroisoquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamideHCID 580088444-amino-1-((8-methyl-1-oxo-2-o-tolyl-1,2-dihydroisoquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acidYield 47%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6386tert-ButanolSolventHCID 12585Pent-2-eneSolvent

Procedure

To a stirred solution of 4-amino-1-((8-methyl-1-oxo-2-o-tolyl-1,2-dihydroisoquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carbaldehyde (compound 4502) (400 mg, 0.94 mmol) in t-BuOH (1.8 mL), a solution of NaH2PO4 (3.90 g, 28.27 mmol) in water (4.8 mL), methyl-2-butene (1.0 mL) and (dropwise) a solution of NaClO2 (767 mg, 6.78 mmol) in water (4.8 mL) were added sequentially. The mixture was stirred at RT for 3 h under an argon atmosphere. The pale yellow solution was acidified with aqueous HCl solution (2 M, 4 mL) to PH=2 and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo, and the residue was triturated with anhydrous ethyl ether and ethyl acetate. The solid was collected by filtration to afford the desired product, 4-amino-1-((8-methyl-1-oxo-2-o-tolyl-1,2-dihydroisoquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxylic acid (compound 4601) (200 mg, 47% yield) as a yellow solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was triturated with anhydrous ethyl ether and ethyl acetate
  7. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-67ad8c01e187479abb7a9cb2bd2908ad
Source dataset
uspto-grants-2015_12
Patent number
US09216982B2

Reaction notes

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