Trifluoroacetic acid → 6-{[2-(Azetidin-3-yl)ethyl](methylsulfonyl)amino}-2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-2H-indazole-3-carboxamide

HRID 2272269ノート

反応式

HRID 2272269 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]([C:17](=[O:20])[NH:18][CH3:19])=[C:15]3[C:10]([CH:11]=[C:12]([N:24]([S:38]([CH3:41])(=[O:40])=[O:39])[CH2:25][CH2:26][CH:27]4[CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28]4)[C:13]([CH:21]4[CH2:23][CH2:22]4)=[CH:14]3)=[N:9]2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:29]1[CH2:30][CH:27]([CH2:26][CH2:25][N:24]([S:38]([CH3:41])(=[O:40])=[O:39])[C:12]2[C:13]([CH:21]3[CH2:22][CH2:23]3)=[CH:14][C:15]3[C:10]([CH:11]=2)=[N:9][N:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[C:16]=3[C:17]([NH:18][CH3:19])=[O:20])[CH2:28]1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 71768611tert-butyl 3-(2-{[2-(4-chlorophenyl)-5-cyclopropyl-3-(methylcarbamoyl)-2H-indazol-6-yl] (methylsulfonyl)amino}ethyl)azetidine-1-carboxylate

生成物 1

HCID 717690346-{[2-(Azetidin-3-yl)ethyl](methylsulfonyl)amino}-2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-2H-indazole-3-carboxamide収率 43.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of tert-butyl 3-(2-{[2-(4-chlorophenyl)-5-cyclopropyl-3-(methylcarbamoyl)-2H-indazol-6-yl](methylsulfonyl)amino}ethyl)azetidine-1-carboxylate (prepared by reacting 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-[(methylsulfonyl)amino]-2H-indazole-3-carboxamide with tert-butyl 3-(2-hydroxyethyl)azetidine-1-carboxylate), (25 mg, 0.04 mmol) in DCM (3 mL) was added TFA (1 mL) and the reaction stirred at ambient temperature. After 1 h, the reaction was concentrated in vacuo and the residue partitioned between EtOAc (25 mL) and aq. saturated sodium bicarbonate (15 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (3×15 mL). The combined organics were washed with brine (15 mL), dried (MgSO4), concentrated in vacuo and purified by preparative HPLC eluting with acetonitrile:0.1% formic acid in water to afford Compound (6) (8.8 mg, 42%). ESI-MS m/z calculated for [M+H]+: 502.2. found: 502.1 1H NMR (400 MHz, CD3CN) δ 8.40 (s, 1H), 7.83 (s, 1H), 7.64-7.54 (m, 4H), 7.39 (s, 1H), 7.37 (br d, J=3.9 Hz, 1H), 3.94-3.81 (m, 2H), 3.76-3.59 (m, 2H), 3.59-3.50 (m, 2H), 3.09 (d, J=10.3 Hz, 3H), 2.97-2.86 (m, 4H), 2.43-2.33 (m, 1H), 1.95-1.86 (m, 2H), 1.14-1.00 (m, 3H), 0.71-0.59 (m, 1H).

後処理

  1. concentrationthe reaction was concentrated in vacuo
  2. customthe residue partitioned between EtOAc (25 mL) and aq. saturated sodium bicarbonate (15 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer extracted with EtOAc (3×15 mL)
  5. washThe combined organics were washed with brine (15 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. custompurified by preparative HPLC
  9. washeluting with acetonitrile

出典と根拠

ORDレコード
ord-0816d9c21f7a4a2cb2d183d2eb90ac80
出典データセット
uspto-grants-2015_09
特許番号
US09120775B2

反応ノート

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