Hydrochloric Acid → HCID 69915157, compound

HRID 402492

Reaction equation

HRID 402492 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C:19]3[C:14](=[N:15][C:16]([O:21][CH2:22][C:23](O)=[O:24])=[CH:17][C:18]=3[CH3:20])[N:13]([CH3:26])[N:12]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C1C=CC2N(O)N=NC=2C=1.Cl.CCN(CC)CC.[CH3:45][O:46][C:47]1[CH:52]=[CH:51][C:50]([C@@H:53]([NH2:55])[CH3:54])=[CH:49][CH:48]=1>C(Cl)Cl.O.C(Cl)CCl>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([C:11]2[C:19]3[C:14](=[N:15][C:16]([O:21][CH2:22][C:23]([NH:55][C@H:53]([C:50]4[CH:51]=[CH:52][C:47]([O:46][CH3:45])=[CH:48][CH:49]=4)[CH3:54])=[O:24])=[CH:17][C:18]=3[CH3:20])[N:13]([CH3:26])[N:12]=2)[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 793467(S)-1-(4-Methoxyphenyl)ethylamineHCID 67209308HCID 67209308, compound

Product 1

HCID 69915157HCID 69915157, compoundYield 12.4%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of [3-(3,5-Dimethoxy-phenyl)-1,4-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yloxy]-acetic acid (building block A1, 100 mg, 0.28 mmol) in CH2Cl2 were added HOBt×H2O (64 mg, 0.42 mmol), EDC×HCl (80 mg, 0.42 mmol) and NEt3 (0.12 ml, 0.84 mmol). After stirring at rt for 5 min, (S)-1-(4-methoxyphenyl)ethanamine (64 mg, 0.42 mmol) was added and stirring continued for 18 h. Then, water was added and the mixture extracted 3 times with DCM. The organic phases were dried over Na2SO4 and the solvent removed under reduced pressure. Purification by reverse phase HPLC (Sunfire C18 OBD column) followed by liberation of the free base (SPE cartridge SCX-1, eluent 7M NH3 in methanol) yielded the title compound (17 mg, 12%). [1H-NMR (DMSO-d6, 600 MHz) δ 8.48 (d, 1H), 7.21 (d, 2H), 6.82 (d, 2H), 6.70 (s, 1H), 6.58 (s, 1H), 5.00-4.88 (m, 1H), 4.87 (d, 1H), 4.83 (d, 1H), 3.85 (s, 3H), 3.78 (s, 6H), 3.70 (s, 3H), 2.37 (s, 3H), 1.37 (d, 3H); UPLC-MS RtJ=1.14 min; [M+H]+=491.2]

Workup

  1. stirringstirring
  2. waitcontinued for 18 h
  3. extractionthe mixture extracted 3 times with DCM
  4. dry with materialThe organic phases were dried over Na2SO4
  5. customthe solvent removed under reduced pressure
  6. customPurification by reverse phase HPLC (Sunfire C18 OBD column)

Sources & evidence

ORD record
ord-e6dcf59335d04c8181b79a90a5b7843a
Source dataset
uspto-grants-2014_06
Patent number
US08742106B2

Linked notes

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