Triethylamine → (R)-2-hydroxy-1-(4-(5-(3-phenoxy-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)propan-1-one

HRID 335168

反応式

HRID 335168 の反応式
[O:1]([C:8]1[C:9]([NH:21][C:22]2[S:26][N:25]=[C:24]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[N:23]=2)=[N:10][CH:11]=[C:12]([S:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:33][C@@H:34]([CH3:38])[C:35](O)=[O:36].Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>CN(C)C1C=CN=CC=1.C(Cl)Cl.O>[OH:33][C@H:34]([CH3:38])[C:35]([N:30]1[CH2:31][CH2:32][CH:27]([C:24]2[N:23]=[C:22]([NH:21][C:9]3[C:8]([O:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:13][C:12]([S:14][C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=4)=[CH:11][N:10]=3)[S:26][N:25]=2)[CH2:28][CH2:29]1)=[O:36]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 107689L-Lactic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 577427923-Phenoxy-N-(3-(piperidin-4-yl)-1,2,4-thiadiazol-5-yl)-5-(pyridin-2-ylthio)pyridin-2-amine

生成物 1

HCID 25099728(R)-2-hydroxy-1-(4-(5-(3-phenoxy-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)propan-1-one収率 27%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

3-Phenoxy-N-(3-(piperidin-4-yl)-1,2,4-thiadiazol-5-yl)-5-(pyridin-2-ylthio)pyridin-2-amine (Example 39, step C, 0.075 g, 0.16 mmol), (S)-2-hydroxypropanoic acid (0.018 g, 0.19 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.047 g, 0.24 mmol), and N,N-dimethylpyridin-4-amine (0.002 g, 0.016 mmol) were dissolved in CH2Cl2 (5 mL). Triethylamine (0.033 g, 0.32 mmol) was added and the solution was stirred at room temperature for 3 hours. Water was added and extracted with CH2Cl2, dried, filtered, and concentrated. The residue was purified by silica gel (1-2% MeOH in CH2Cl2) to give (R)-2-hydroxy-1-(4-(5-(3-phenoxy-5-(pyridin-2-ylthio)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)piperidin-1-yl)propan-1-one (0.023 g, 27% yield). 1H NMR (d6-DMSO) δ 12.34 (s, 1H), 8.39 (d, 1H), 8.37 (m, 1H), 7.66 (dt, 1H), 7.47 (d, 1H), 7.42 (t, 2H), 7.21-7.11 (m, 5H), 4.82 (t, 1H), 4.45 (m, 1H), 4.34 (m, 1H), 4.01 (m, 1H), 3.25-3.04 (m, 2H), 2.84 (m, 1H), 2.02 (d, 2H), 1.81-1.55 (m, 2H), 1.18 (d, 3H).

後処理

  1. extractionextracted with CH2Cl2
  2. customdried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel (1-2% MeOH in CH2Cl2)

出典と根拠

ORDレコード
ord-51b3d179bd134f02b4201b3439ae9db8
出典データセット
uspto-grants-2014_11
特許番号
US08883828B2

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