Hydrochloric Acid → HCID 69915157、化合物

HRID 402492

反応式

HRID 402492 の反応式
[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

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 793467(S)-1-(4-Methoxyphenyl)ethylamineHCID 67209308HCID 67209308、化合物

生成物 1

HCID 69915157HCID 69915157、化合物収率 12.4%

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 962Water溶媒2 回HCID 6344Dichloromethane溶媒

実験手順

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]

後処理

  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)

出典と根拠

ORDレコード
ord-e6dcf59335d04c8181b79a90a5b7843a
出典データセット
uspto-grants-2014_06
特許番号
US08742106B2

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