4-Hydroxybenzaldehyde → HCID 178486497, compound

HRID 253231Notes

Reaction equation

[NH2:1][C:2]1[NH:6][N:5]=[C:4]([CH3:7])[C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH:16]2[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]2)=[C:10]([O:29][CH3:30])[CH:9]=1.[OH:31][C:32]1[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][CH:33]=1.[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41]>CN(C=O)C>[F:43][C:42]([F:45])([F:44])[C:40]([OH:46])=[O:41].[CH3:7][C:4]1[C:3]2[C:8]3[CH:9]=[C:10]([O:29][CH3:30])[C:11]([O:14][CH2:15][CH:16]4[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]4)=[CH:12][C:13]=3[C:36]([C:35]3[CH:38]=[CH:39][C:32]([OH:31])=[CH:33][CH:34]=3)=[N:1][C:2]=2[NH:6][N:5]=1

Participants

Conditions

Temperature: 75 °C

Procedure

A mixture of 1,1-dimethylethyl 4-({[4-(5-amino-3-methyl-1H-pyrazol-4-yl)-2-(methyloxy)phenyl]oxy}methyl)piperidine-1-carboxylate (100 mg, 0.24 mmol) and 4-hydroxybenzaldehyde (44 mg, 0.36 mmol) was dissolved in TFA (1 mL) and heated to 75° C. for 15 h. After cooling to rt, the mixture was diluted with DMF and purified by preparative reverse phase HPLC. The fractions containing the desired product were concentrated and lyophilized to yield 4-{1-methyl-8-(methyloxy)-7-[(piperidin-4-ylmethyl)oxy]-3H-pyrazolo[3,4-c]isoquinolin-5-yl)phenol hydrogen trifluoroacetate (26.2 mg, 20% yield). 1H NMR (400 MHz, d6-DMSO): 8.64-8.54 (m, 1H), 8.28-8.18 (m, 1H), 7.64 (s, 1H), 7.57-7.54 (m, 2H), 7.49 (s, 1H), 6.95-6.91 (m, 2H), 4.05 (s, 3H), 3.82 (d, 2H), 3.31 (d, 2H), 2.92 (q, 2H), 2.81 (s, 3H), 2.16-2.04 (m, 1H), 1.94 (d, 2H), 1.53-1.42 (m, 2H); MS (EI) for C24H26N4O3: 419 (MH+).

Workup

temperatureAfter cooling to rt
custompurified by preparative reverse phase HPLC
additionThe fractions containing the desired product
concentrationwere concentrated

Sources & evidence

ORD record: ord-e33631aae47342ffa36f64579ad85633
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07872014B2

Reaction notes

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