Hydrochloric Acid → 3-(2-(4-aminopiperidin-1-yl)pyrimidin-4-yl)-N,N-dimethyl-1H-indazole-5-carboxamide

HRID 1529446ノート

反応式

HRID 1529446 の反応式
[CH3:1][N:2]([CH3:40])[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10](C1CCCCO1)[N:9]=[C:8]2[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([N:26]2[CH2:31][CH2:30][CH:29]([NH:32]C(=O)OC(C)(C)C)[CH2:28][CH2:27]2)[N:21]=1)=[O:4].Cl>CCOC(C)=O>[NH2:32][CH:29]1[CH2:30][CH2:31][N:26]([C:22]2[N:21]=[C:20]([C:8]3[C:7]4[C:11](=[CH:12][CH:13]=[C:5]([C:3]([N:2]([CH3:40])[CH3:1])=[O:4])[CH:6]=4)[NH:10][N:9]=3)[CH:25]=[CH:24][N:23]=2)[CH2:27][CH2:28]1

参加物

4

反応物 2

HCID 313Hydrochloric AcidHCID 86709796tert-butyl (1-(4-(5-(dimethylcarbamoyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrimidin-2-yl)piperidin-4-yl)carbamate

生成物 1

HCID 679767933-(2-(4-aminopiperidin-1-yl)pyrimidin-4-yl)-N,N-dimethyl-1H-indazole-5-carboxamide収率 56.4%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of tert-butyl (1-(4-(5-(dimethylcarbamoyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrimidin-2-yl)piperidin-4-yl)carbamate (0.4 g, 0.728 mmol) in EtOAc (8 mL) was added HCl (4 N in dioxane, 8 mL) and the reaction was stirred at RT for 3 h The mixture was quenched with water and neutralized with NaHCO3 and extracted with EtOAc. The organic layer was separated and dried over Na2SO4, filtered and concentrated. The residue was purified with HPLC (5-50% MeCN in water with 0.1% TFA) to give 3-(2-(4-aminopiperidin-1-yl)pyrimidin-4-yl)-N,N-dimethyl-1H-indazole-5-carboxamide (150 mg, 52%) as an off white solid. MS (ESI, pos. ion) m/z: 366.2 (M+1); 1H NMR (300 MHz, DMSO-d6): −δ 13.88 (s, 1H), 8.53 (s, 1H), 8.48 (d, 2 H, J=5.1 Hz), 7.96 (s, 3H), 7.70 (d, 1 H, J=8.6 Hz), 7.52 (dd, 1 H, J=8.6, 1.4 Hz), 7.38 (d, 1 H, J=5.1 Hz), 4.77 (d, 2 H, J=13.6 Hz), 3.41 (bs, 1H), 3.09-3.20 (m, 2H), 3.03 (s, 6H), 2.03 (d, 2 H, J=10.5 Hz), 1.47-1.58 (m, 2H).

後処理

  1. customwas quenched with water and neutralized with NaHCO3
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified with HPLC (5-50% MeCN in water with 0.1% TFA)

出典と根拠

ORDレコード
ord-52a59c7361604ea6851f837386fdeab4
出典データセット
uspto-grants-2015_07
特許番号
US09090593B2

反応ノート

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