Hydrochloric Acid → HCID 178502473、化合物

HRID 1751615ノート

反応式

HRID 1751615 の反応式
Cl.O1CCOCC1.[Br:8][C:9]1[CH:10]=[C:11]2[C:33](=[CH:34][CH:35]=1)[C:15]1[NH:16][C:17]([C@@H:19]3[C@H:24]4[CH2:25][C@H:21]([CH2:22][CH2:23]4)[N:20]3C(OC(C)(C)C)=O)=[N:18][C:14]=1[CH:13]=[CH:12]2.[CH3:36][O:37][C:38]([NH:40][C@@H:41]([CH:45]([CH3:47])[CH3:46])[C:42](O)=[O:43])=[O:39].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CO>[Br:8][C:9]1[CH:10]=[C:11]2[C:33](=[CH:34][CH:35]=1)[C:15]1[NH:16][C:17]([C@@H:19]3[C@H:24]4[CH2:25][C@H:21]([CH2:22][CH2:23]4)[N:20]3[C:42](=[O:43])[C@@H:41]([NH:40][C:38](=[O:39])[O:37][CH3:36])[CH:45]([CH3:47])[CH3:46])=[N:18][C:14]=1[CH:13]=[CH:12]2

参加物

9

反応物 6

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 178452510HCID 178452510、化合物

生成物 1

HCID 178502473HCID 178502473、化合物収率 99%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒3 回

実験手順

Hydrogen chloride in dioxane solution (4N, 6.78 mL, 27.18 mmol) was added to (1S,3S,4R)-tert-butyl 3-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (0.80 g, 1.81 mmol) in methylene chloride:methanol (18.1 mL: 3.6 mL). The suspension was allowed to stir at room temperature for one hour. Upon completion by LCMS, the reaction was concentrated to dryness and the crude product (assumed 1.81 mmol) was suspended in methylene chloride (18 mL). (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (0.38 g, 2.17 mmol) and DIPEA (1.58 mL, 9.04 mmol) were added to the slurry. HATU (1.03 g, 2.71 mmol) was added and the reaction was stirred at room temperature for 3 hours. Upon completion, the crude reaction was diluted in methylene chloride and washed with 1N HCl, and aqueous sodium bicarbonate. The organic layer was concentrated and purified by normal phase chromatography (40-80% ethyl acetate (5% methanol) in hexanes) to give methyl (S)-1-((1S,3S,4R)-3-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-3-methyl-1-oxobutan-2-ylcarbamate (0.949, >99%).

後処理

  1. concentrationUpon completion by LCMS, the reaction was concentrated to dryness
  2. stirringthe reaction was stirred at room temperature for 3 hours
  3. customUpon completion, the crude reaction
  4. washwashed with 1N HCl, and aqueous sodium bicarbonate
  5. concentrationThe organic layer was concentrated
  6. custompurified by normal phase chromatography (40-80% ethyl acetate (5% methanol) in hexanes)

出典と根拠

ORDレコード
ord-75cfc73e60a549e684ebcc8437553a89
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

反応ノート

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