Hydrochloric Acid → 1-methylethyl((cis)-1-acetyl-6-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate hydrochloride

HRID 2366925

반응식

HRID 2366925 반응식
CC([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)C.[CH3:31][CH:32](OC(=O)NC1C2C(=CC=C(B3OC(C)(C)C(C)(C)O3)C=2)N(C(=O)C)C(C)C1)[CH3:33].Br[C:62]1[CH:63]=[N:64][N:65]([CH2:67][CH2:68][N:69]([CH3:71])[CH3:70])[CH:66]=1.C(=O)([O-])[O-].[K+].[K+].[ClH:78].CO>C(O)C.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>[ClH:78].[CH3:31][CH:32]([N:6]([C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:62]3[CH:63]=[N:64][N:65]([CH2:67][CH2:68][N:69]([CH3:71])[CH3:70])[CH:66]=3)[CH:15]=2)[N:10]([C:26](=[O:28])[CH3:27])[C@@H:9]([CH3:29])[CH2:8]1)[C:5](=[O:30])[OH:4])[CH3:33]

참가 물질

9

반응물 6

HCID 313Hydrochloric AcidHCID 887MethanolHCID 11430Potassium CarbonateHCID 21859709[2-(4-Bromopyrazol-1-yl)ethyl]dimethylamineHCID 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 867623481-methylethyl((cis)-1-acetyl-6-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate hydrochloride

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매

반응 조건

온도
85 °C

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) (120 mg, 0.288 mmol), [2-(4-bromo-1H-pyrazol-1-yl)ethyl]dimethylamine (for a preparation see Intermediate 15) (85 mg, 0.390 mmol) and potassium carbonate (51.8 mg, 0.375 mmol) were stirred in ethanol (1.5 ml) and toluene (1.5 ml) and the mixture degassed. Tetrakis(triphenylphosphine)palladium(0) (16.65 mg, 0.014 mmol) was added, the mixture degassed again and heated to reflux (85° C.) overnight. The mixture was cooled to room temperature, partitioned between ethyl acetate (35 ml) and sat. sodium hydrogen carbonate:water (1:1, 10 ml). The aqueous layer was run off and the organic washed (sat. sodium hydrogen carbonate:water (1:1, 10 ml)), dried (magnesium sulfate) and evaporated to an orange residue. The residue was loaded on to a 12+M Biotage silica column and eluted with DCM:2M Methanolic ammonia (0 to 15%). The product containing fractions were evaporated to dryness then dissolved in MeOH (1 ml) and 1.25M HCl in MeOH (0.128 ml, 0.159 mmol) was added and the mixture evaporated to an off white solid (59 mg). LCMS (Method C): Rt=0.64, MH+=428

후처리

  1. customtoluene (1.5 ml) and the mixture degassed
  2. customthe mixture degassed again
  3. temperatureheated
  4. temperatureThe mixture was cooled to room temperature
  5. custompartitioned between ethyl acetate (35 ml) and sat. sodium hydrogen carbonate:water (1:1, 10 ml)
  6. washthe organic washed (sat. sodium hydrogen carbonate:water (1:1, 10 ml))
  7. dry with materialdried (magnesium sulfate)
  8. customevaporated to an orange residue
  9. washeluted with DCM
  10. additionThe product containing fractions
  11. customwere evaporated to dryness
  12. dissolutionthen dissolved in MeOH (1 ml)
  13. customthe mixture evaporated to an off white solid (59 mg)

출처 및 근거

ORD 기록
ord-97a800e0c9b3405d9622a642b1e21b99
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697725B2

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