1,2-Dimethoxyethane → methyl 6-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinate

HRID 882261ノート

反応式

HRID 882261 の反応式
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10](B3OC(C)(C)C(C)(C)O3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2].Br[C:33]1[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][N:34]=1.C(=O)([O-])[O-].[K+].[K+].COCCOC>CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:33]3[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][N:34]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:30])[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2]

参加物

7

反応物 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 13349623Methyl 6-bromopyridine-3-carboxylateHCID 86709429Tert-butyl ((2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinolin-4-yl)carbamate

生成物 1

HCID 86709428methyl 6-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinate

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 887Methanol溶媒

実験手順

In a separate vial, Tert-butyl ((2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinolin-4-yl)carbamate (for a preparation see Intermediate 61) (2.2 g, 5.11 mmol), methyl 6-bromonicotinate (1.325 g, 6.13 mmol), Pd(PPh3)4 (0.591 g, 0.511 mmol) and potassium carbonate (2.120 g, 15.34 mmol) were combined in methanol (10 mL) and DME (3 mL) and heated under microwave irradiation to 100° C. for 70 mins. The two reaction mixtures were combined and partitioned between water (150 mL) and DCM (3×150 mL). The aqueous layer was acidified to pH 3 via the addition of aq. HCl and extracted with DCM (3×100 mL). The combined organic layers were dried by passing through a hydrophobic frit, and concentrated in vacuo to give crude methyl 6-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinate (2.2 g) which was used directly in the next step without further purification. LCMS: (Formate, 2 min), Rt=1.06 min, MH+440.

後処理

  1. customThe two reaction mixtures
  2. custompartitioned between water (150 mL) and DCM (3×150 mL)
  3. additionThe aqueous layer was acidified to pH 3 via the addition of aq. HCl
  4. extractionextracted with DCM (3×100 mL)
  5. customThe combined organic layers were dried
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-17fcdb140d6444b3842cef5abe19b6f9
出典データセット
uspto-grants-2015_03
特許番号
US08993554B2

反応ノート

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