Picolinic acid → Pyridine-2-carboxylic acid (3-hydroxy-adamantan-1-yl)-amide

HRID 218022

반응식

HRID 218022 반응식
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([OH:9])=O.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[NH2:41][C:42]12[CH2:51][CH:46]3[CH2:47][CH:48]([CH2:50][C:44]([OH:52])([CH2:45]3)[CH2:43]1)[CH2:49]2>CN(C=O)C>[OH:52][C:44]12[CH2:50][CH:48]3[CH2:47][CH:46]([CH2:51][C:42]([NH:41][C:7]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)=[O:9])([CH2:49]3)[CH2:43]1)[CH2:45]2

참가 물질

6

반응물 4

HCID 1018Picolinic acidHCID 8471TriethylamineHCID 6586453-Amino-1-adamantanolHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

생성물 1

HCID 59161068Pyridine-2-carboxylic acid (3-hydroxy-adamantan-1-yl)-amide수율 97%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a 40 ml vial was added picolinic acid (0.68 g, 5.5 mmol), DMF (15 ml), triethylamine (0.90 mL, 6.4 mmol), and O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 2.3 g, 6.0 mmol). The mixture was stirred at rt for 5 minutes to get a clear solution. 3-Amino-adamantanol (0.84 g, 5.0 mmol; AK Scientific, 897-4G Independence Ave., Mountain View, Calif. 94043) was added to the above solution and stirred at rt for 2 hours. DMF was removed in Genevac and the residue was dissolved in DCM (20 mL), washed with 1N aqueous NaOH, water and brine, dried over Na2SO4, and concentrated under reduced pressure to afford 1.32 g (97%) of crude title compound, pyridine-2-carboxylic acid (3-hydroxy-adamantan-1-yl)-amide, as an oil, which became a colorless solid upon standing at room temperature. LC/MS (Gradient: acetonitrile in water, 20-85%, in 1.7 minutes with a cycle time of 2 min. Flow rate: 5.0 mL/min. Mobile phase additive: 30 mM of ammonium formate. Column: Inertsil® ODS-3, 50×4.6 mm, 3 μm particle size (GL Sciences, Tokyo, Japan)): Retention time: 0.79 min; purity (UV254): 100%; ESI-MS m/z: 273 (M+H)+. It was used in the next step without further purification.

후처리

  1. customto get a clear solution
  2. stirringstirred at rt for 2 hours
  3. customDMF was removed in Genevac
  4. dissolutionthe residue was dissolved in DCM (20 mL)
  5. washwashed with 1N aqueous NaOH, water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-b7edd756cefe4ed9ae60ac6daff93c1d
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08198275B2

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