4-Hydroxybenzaldehyde → HCID 178487361, compound

HRID 253237Notes

Reaction equation

HRID 253237 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][CH:11]=[C:10]([O:14][CH3:15])[C:9]=1[O:16][CH2:17][CH:18]1[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]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]>>[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[C:9]([O:16][CH2:17][CH:18]4[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]4)=[C:10]([O:14][CH3:15])[CH:11]=[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

4

Reactant 3

HCID 1264-HydroxybenzaldehydeHCID 6422Trifluoroacetic acidHCID 178489812HCID 178489812, compound

Product 1

HCID 178487361HCID 178487361, compoundYield 13%

Conditions

Temperature
75 °C

Procedure

To 1,1-dimethylethyl 4-({[2-(5-amino-3-methyl-1H-pyrazol-4-yl)-6-(methyloxy)phenyl]oxy}methyl}piperidine-1-carboxylate (397 mg, 0.95 mmol) was added 4-hydroxybenzaldehyde (174 mg, 1.4 mmol) and TFA (5 mL). The mixture was heated to 75° C. and stirred for 15 h. After cooling to rt, the volatile materials were removed in vacuo. The resulting residue was dissolved in a 1:1 mixture of water:acetonitrile and purified by preparative HPLC. The fractions containing the desired product were concentrated and lyophilized to provide 4-{1-methyl-8-(methyloxy)-9-[(piperidin-4-ylmethyl)oxy]-3H-pyrazolo[3,4-c]isoquinolin-5-yl}phenol trifluoroacetate (64.1 mg, 0.12 mmol, 13% yield). 1H NMR (400 MHz, DMSO-d6): δ9.81 (br s, 1H), 8.53 (br d, 1H), 8.21 (br m, 1H), 7.84 (d, 1H), 7.43 (m, 2H), 7.38 (d, 1H), 6.92 (m, 2H), 3.97 (s, 3H), 3.88 (d, 2H), 3.32 (br d, 2H), 3.00-2.92 (q, 2H), 2.80 (s, 3H), 2.26 (m, 1H), 2.04 (br d, 2H), 1.52-1.43 (m, 2H); MS (EI) for C24H26N4O3: 419 (MH+).

Workup

  1. temperatureAfter cooling to rt
  2. customthe volatile materials were removed in vacuo
  3. dissolutionThe resulting residue was dissolved in a 1:1 mixture of water
  4. customacetonitrile and purified by preparative HPLC
  5. additionThe fractions containing the desired product
  6. concentrationwere concentrated

Sources & evidence

ORD record
ord-1a9e19ff861d4f7ca67258eea1bbe189
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

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