Potassium Carbonate → 1-Methylethyl [(cis)-1-acetyl-6-(2-formyl-1,3-thiazol-4-yl)-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate

HRID 2366849ノート

反応式

HRID 2366849 の反応式
[CH3:1][CH:2]([O:4][C:5](=[O:30])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](B3OC(C)(C)C(C)(C)O3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[CH3:3].CC(OC(=O)NC1C2C(=CC=C(B3OC(C)(C)C(C)(C)O3)C=2)N(C(=O)C)C(C)C1)C.Br[C:62]1[N:63]=[C:64]([CH:67]=[O:68])[S:65][CH:66]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)C.C1(C)C=CC=CC=1.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>[CH3:3][CH:2]([O:4][C:5](=[O:30])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:62]3[N:63]=[C:64]([CH:67]=[O:68])[S:65][CH:66]=3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[CH3:1]

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 27631874-Bromothiazole-2-carboxaldehydeHCID 681853941-Methylethyl [(cis)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamateHCID 774200021-Methylethyl [1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate

生成物 1

HCID 866692321-Methylethyl [(cis)-1-acetyl-6-(2-formyl-1,3-thiazol-4-yl)-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 702Ethanol溶媒HCID 1140Toluene溶媒

実験手順

1-methylethyl[(cis)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 12) (50 mg, 0.120 mmol) was mixed with 4-bromo-1,3-thiazole-2-carbaldehyde (34.6 mg, 0.180 mmol, available from Frontier), potassium carbonate (33.2 mg, 0.240 mmol), tetrakis(triphenylphosphine)palladium(0) (6.94 mg, 6.01 μmol) and dissolved in ethanol (0.5 mL) and toluene (0.5 mL). The mixture was heated in a nitrogen-flushed microwave vial at 90° C. for 1 hour in a Biotage initiator and the mixture was left to cool to room temperature overnight. The residue was partitioned between distilled water (20 mL) and EtOAc (60 mL). The aqueous layer was extracted with EtOAc (60 mL) and the organic fractions were combined, washed (brine (50 mL)), dried (sodium sulfate), filtered and evaporated to dryness to give a yellow solid. This was purified on a 12+M Biotage silica column eluting with a 0-60% gradient of ethyl acetate in cyclohexane. Product-containing fractions were evaporated to dryness to give a clear, colourless solid (23 mg). LCMS (Method C): Rt=0.96, MH+=402

後処理

  1. temperatureThe mixture was heated in a nitrogen-
  2. customflushed microwave vial at 90° C. for 1 hour in a Biotage initiator
  3. waitthe mixture was left
  4. customThe residue was partitioned
  5. distillationbetween distilled water (20 mL) and EtOAc (60 mL)
  6. extractionThe aqueous layer was extracted with EtOAc (60 mL)
  7. washwashed (brine (50 mL))
  8. dry with materialdried (sodium sulfate)
  9. filtrationfiltered
  10. customevaporated to dryness
  11. customto give a yellow solid
  12. customThis was purified on a 12+M Biotage silica column
  13. washeluting with a 0-60% gradient of ethyl acetate in cyclohexane
  14. customProduct-containing fractions were evaporated to dryness

出典と根拠

ORDレコード
ord-8bb11382a5ff43999e6be29913fe8806
出典データセット
uspto-grants-2014_04
特許番号
US08697725B2

反応ノート

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