Formic Acid → HCID 178487363, compound

HRID 253238Notes

Reaction equation

[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:8][C:9]1[C:21]2[C:20]3[C:19]([O:22][CH2:23][CH:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)=[C:18]([O:30][CH3:31])[CH:17]=[CH:16][C:15]=3[C:14]([C:32]3[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=3)=[N:13][C:12]=2[NH:11][N:10]=1.C=O.[CH:41](O)=O>O>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:8][C:9]1[C:21]2[C:20]3[C:19]([O:22][CH2:23][CH:24]4[CH2:29][CH2:28][N:27]([CH3:41])[CH2:26][CH2:25]4)=[C:18]([O:30][CH3:31])[CH:17]=[CH:16][C:15]=3[C:14]([C:32]3[CH:33]=[CH:34][C:35]([OH:38])=[CH:36][CH:37]=3)=[N:13][C:12]=2[NH:11][N:10]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To 4-{1-methyl-8-(methyloxy)-9-[(piperidin-4-ylmethyl)oxy]-3H-pyrazolo[3,4-c]isoquinolin-5-yl)phenol hydrogen trifluoroacetate (47 mg, 0.11 mmol) was added 37% aqueous formaldehyde (10 μL) and formic acid (150 μL). The mixture was heated to 110° C. for 1.5 h before cooling to rt. The mixture was diluted with a 1:1 mixture of water:acetonitrile and purified by preparative HPLC. The fractions containing desired product were combined, concentrated, and lyophilized to provide 4-(1-methyl-8-(methyloxy)-9-{[(1-methylpiperidin-4-yl)methyl]oxy}-3H-pyrazolo[3,4-c]isoquinolin-5-yl)phenol trifluoroacetate (14.1 mg, 0.026 mmol, 23% yield). 1H NMR (400 MHz, DMSO-d6): δ9.93 (br m, 2H), 7.87 (d, 1H), 7.48 (d, 2H), 7.44 (d, 1H), 6.96 (m, 2H), 4.00 (s, 3H), 3.45 (m, 2H), 3.00-2.96 (q, 2H), 2.83 (s, 3H), 2.74 (d, 3 h), 2.18 (m, 1H), 2.09 (br d, 2H), 1.61-1.52 (m, 2H); MS (EI) for C25H28N4O3: 433 (MH+).

Workup

temperaturebefore cooling to rt
customacetonitrile and purified by preparative HPLC
additionThe fractions containing desired product
concentrationconcentrated

Sources & evidence

ORD record: ord-b787fd49f0c1434db60337d8a520200a
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07872014B2

Reaction notes

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