1,2-Dichloroethane → (3R,6S)-3-Amino-6-(2,3-difluorophenyl)-1-pyridin-4-ylazepan-2-one

HRID 493659

反応式

HRID 493659 の反応式
C(OC([N:8](C(OC(C)(C)C)=O)[C@@H:9]([C:23]([OH:25])=O)[CH2:10][CH2:11][C@@H:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=1[F:22])[CH2:13][NH2:14])=O)(C)(C)C.ClCC(C)(O)C.C(N(C(C)C)CC)(C)C.C(Cl)CCl.[CH:52]1[CH:57]=[N:56][C:55]2N(O)N=N[C:54]=2[CH:53]=1.C([O-])(O)=O.[Na+]>CCO.C(Cl)Cl>[NH2:8][C@@H:9]1[CH2:10][CH2:11][C@@H:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=2[F:22])[CH2:13][N:14]([C:53]2[CH:52]=[CH:57][N:56]=[CH:55][CH:54]=2)[C:23]1=[O:25]

参加物

9

反応物 6

HCID 111,2-DichloroethaneHCID 684091-Chloro-2-methylpropan-2-olHCID 81531Diisopropylethylamine2 回HCID 181649HOAtHCID 516892Sodium BicarbonateHCID 67526479(5S)-N2,N2-Bis(tert-butoxycarbonyl)-5-(2,3-difluorophenyl)-D-lysine

生成物 1

HCID 60037853(3R,6S)-3-Amino-6-(2,3-difluorophenyl)-1-pyridin-4-ylazepan-2-one収率 53.4%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 6344Dichloromethane溶媒

実験手順

A solution of (5S)—N2,N2-bis(tert-butoxycarbonyl)-5-(2,3-difluorophenyl)-D-lysine (0.569 g, 1.24 mmol), 1-chloro-2-methyl-2-propanol (0.202 g, 1.86 mmol) and diisopropylethylamine (0.529 g, 4.10 mmol) in EtOH (5 mL) was heated at 75° C. overnight. The reaction was concentrated to dryness, diluted with DCM (20 mL) and EDC (0.358 g, 1.87 mmol), HOAT (0.252 g, 1.87 mmol) were added followed by diisopropylethylamine (0.650 mL, 3.73 mmol). After stirring overnight, NaHCO3 was added, the layers separated and the aqueous phase backwashed with DCM. The combined organics were dried over magnesium sulfate, filtered, concentrated and the residue purified by silica gel chromatography (10%→35% EtOAc/hexanes) to give the title compound (0.21 g). MS 513.1 (M+1). 1H NMR (500 MHz, CD3OD) δ 7.1 (m, 3H), 5.24 (d, J=10.7 Hz, 1H), 4.02 (m, 1H), 3.69 (d, J=13.9 Hz, 1H), 3.60 (d, J=15.1 Hz, 1H), 3.39 (m, 1H), 3.24 (d, J=14.2 Hz, 1H), 2.4 (m, 1H), 2.1 (m, 3H), 1.5 (s, 18H), 1.20 (s, 3H), 1.16 (s, 3H).

後処理

  1. concentrationThe reaction was concentrated to dryness
  2. additionwere added
  3. customthe layers separated
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue purified by silica gel chromatography (10%→35% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-db959a8a34e94f988ed35fc7e988f804
出典データセット
uspto-grants-2009_05
特許番号
US07534784B2

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