1,2-Dichloroethane → (R)-3-{[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 245825

反応式

HRID 245825 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([OH:23])=O)=[CH:19][N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[NH2:32][C@@H:33]1[CH2:38][CH2:37][CH2:36][N:35]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:34]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:42]([O:41][C:39]([N:35]1[CH2:36][CH2:37][CH2:38][C@@H:33]([NH:32][C:21]([C:20]2[C:14]3[C:15](=[N:16][CH:17]=[C:12]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=5)[N:8]([CH3:11])[N:7]=4)[N:13]=3)[N:18]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[CH:19]=2)=[O:23])[CH2:34]1)=[O:40])([CH3:45])([CH3:43])[CH3:44]

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 712796712-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

生成物 1

HCID 71280608(R)-3-{[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester収率 83.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A round-bottomed flask was charged with 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (120 mg, 0.26 mmol), (R)-tert-butyl 3-aminopiperidine-1-carboxylate (80 mg, 0.40 mmol), HOBT (45 mg, 0.29 mmol) and EDC (56 mg, 0.29 mmol). DMF (1.2 ml) was added followed by N,N-diisopropylethylamine (0.10 ml, 0.57 mmol). The reaction mixture was stirred at room temperature for 48 h then quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-50% EtOAc) to provide 139 mg (83%) of (R)-3-{[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester as a light yellow solid.

後処理

  1. customthen quenched with water
  2. extractionextracted with diethyl ether (2×)
  3. washThe combined organic layers were washed twice with water and once with brine
  4. dry with materialthen dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-50% EtOAc)

出典と根拠

ORDレコード
ord-508d617bd87f4f68a2b2654f0d4828d4
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

関連ノート

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