Water → (R)-5-(1-(7-azaspiro[3.5]nonan-2-yl)-1H-pyrazol-4-yl)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine

HRID 587121ノート

反応式

HRID 587121 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][N:11]([CH:13]3[CH2:16][C:15]4([CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]4)[CH2:14]3)[CH:12]=2)=[CH:4][C:3]=1[O:29][C@@H:30]([C:32]1[C:37]([Cl:38])=[CH:36][CH:35]=[C:34]([F:39])[C:33]=1[Cl:40])[CH3:31].C([O-])([O-])=O.[Na+].[Na+].O>C(O)=O.CCOC(C)=O>[CH2:14]1[C:15]2([CH2:17][CH2:18][NH:19][CH2:20][CH2:21]2)[CH2:16][CH:13]1[N:11]1[CH:12]=[C:8]([C:5]2[CH:4]=[C:3]([O:29][C@@H:30]([C:32]3[C:37]([Cl:38])=[CH:36][CH:35]=[C:34]([F:39])[C:33]=3[Cl:40])[CH3:31])[C:2]([NH2:1])=[N:7][CH:6]=2)[CH:9]=[N:10]1

参加物

6

反応物 3

HCID 962WaterHCID 10340Sodium CarbonateHCID 71240056(R)-tert-butyl 2-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate

生成物 1

HCID 71240011(R)-5-(1-(7-azaspiro[3.5]nonan-2-yl)-1H-pyrazol-4-yl)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine収率 88.2%

試薬・触媒・溶媒 2

HCID 284Formic Acid溶媒HCID 8857Ethyl Acetate溶媒

実験手順

(R)-tert-butyl 2-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate (105 mg, 0.178 mmol, 1.0 equiv) was dissolved in formic acid (6 mL). The solution was sonicated at room temperature for 90 min (the temperature of sonication bath reached about 40° C. after 90 min). The solution was cooled to room temperature and concentrated by rotavapor to give the residue which was dissolved in EtOAc (20 mL). A solution of Na2CO3 (2.0 M, 20 mL) was added. The mixture was stirred at room temperature for 30 min. H2O (10 mL) was added. The layers were separated. The aqueous phase was extracted with DCM (3×30 mL). The combined organic phase was washed with brine (30 mL), dried over anhydrous Na2SO4, concentrated to give pale yellow solid which was purified by CombiFlash [12 g silica gel column; (MeOH/NH4OH=10/1)/DCM: 0-20%] to afford 77 mg (yield 88%) of (R)-5-(1-(7-azaspiro[3.5]nonan-2-yl)-1H-pyrazol-4-yl)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine as a off-white foam solid.

後処理

  1. customThe solution was sonicated at room temperature for 90 min (
  2. customthe temperature of sonication bath
  3. concentrationconcentrated by rotavapor
  4. customto give the residue which
  5. customThe layers were separated
  6. extractionThe aqueous phase was extracted with DCM (3×30 mL)
  7. washThe combined organic phase was washed with brine (30 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated
  10. customto give pale yellow solid which
  11. customwas purified by CombiFlash [12 g silica gel column; (MeOH/NH4OH=10/1)/DCM: 0-20%]

出典と根拠

ORDレコード
ord-af896080e51a4cd89c4cdaee491ea0dd
出典データセット
uspto-grants-2016_01
特許番号
US09226923B2

反応ノート

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