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 2366849노트

반응식

HRID 2366849 반응식
[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]

참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 1140Toluene용매

실험 절차

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

후처리

  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

출처 및 근거

ORD 기록
ord-8bb11382a5ff43999e6be29913fe8806
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697725B2

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