Potassium Phosphate, Tribasic → Tert-butyl 4-(5-(2-(3-ethylureido)-6-fluorobenzo[d]thiazol-5-yl)pyrimidin-2-yl)piperazine-1-carboxylate

HRID 2068688노트

반응식

HRID 2068688 반응식
Br[C:2]1[C:3]([F:17])=[CH:4][C:5]2[S:9][C:8]([NH:10][C:11]([NH:13][CH2:14][CH3:15])=[O:12])=[N:7][C:6]=2[CH:16]=1.CC1(C)C(C)(C)OB([C:26]2[CH:27]=[N:28][C:29]([N:32]3[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]3)=[N:30][CH:31]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:14]([NH:13][C:11](=[O:12])[NH:10][C:8]1[S:9][C:5]2[CH:4]=[C:3]([F:17])[C:2]([C:26]3[CH:31]=[N:30][C:29]([N:32]4[CH2:33][CH2:34][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:36][CH2:37]4)=[N:28][CH:27]=3)=[CH:16][C:6]=2[N:7]=1)[CH3:15]

참가 물질

6

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 46739020tert-Butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperazine-1-carboxylateHCID 596030721-(5-Bromo-6-fluoro-benzothiazol-2-yl)-3-ethyl-urea

생성물 1

HCID 59603081Tert-butyl 4-(5-(2-(3-ethylureido)-6-fluorobenzo[d]thiazol-5-yl)pyrimidin-2-yl)piperazine-1-carboxylate수율 20%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 21962138N,N-Dimethylformamide--water (1/1)용매

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온도
97.5 °C

실험 절차

A solution of 1-(5-bromo-6-fluoro-benzothiazol-2-yl)-3-ethyl-urea (0.05 g, 0.15 mmol), tert-butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperazine-1-carboxylate (0.12 g, 0.31 mmol) and K3PO4 (0.13 g, 0.61 mmol) in DMF-H2O (5.0 mL, 3:2) was degassed by flushing with nitrogen for 15 min. Dichlorobis(triphenylphosphine)-palladium(II) (0.021 g, 0.03 mmol) was then added to the reaction mixture followed by degassing with nitrogen for another 15 min. The resulting reaction mixture was then heated to 95-100° C. for 2 h. After the completion of the reaction (TLC monitoring), the reaction mixture was cooled to room temperature and poured onto ice-cold water followed by extraction with EtOAc (2×50 mL). The combined organics was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude was then purified over silica gel (100-200 M, 1.60% MeOH-DCM) to obtain the desired product (0.015 g, 20%). 1H-NMR (400 MHz, DMSO-d6): δ 1.08 (t, J=7.20 Hz, 3H), 1.43 (s, 9H), 3.20 (m, 2H), 3.42 (br s, 4H), 3.79 (br s, 4H), 6.71 (br s, 1H), 7.76 (d, J=6.80 Hz, 1H), 7.92 (d, J=10.40 Hz, 1H), 8.62 (s, 2H) and 10.74 (br s, 1H). MS: 502.27 (M+H)+. Qualitative HPLC Purity (Acquity BEH C-18, 100×2.1 mm, 272 nm): 99.21% (Rt=6.51 min).

후처리

  1. customby flushing with nitrogen for 15 min
  2. customby degassing with nitrogen for another 15 min
  3. customThe resulting reaction mixture
  4. customAfter the completion of the reaction (TLC monitoring)
  5. temperaturethe reaction mixture was cooled to room temperature
  6. additionpoured onto ice-cold water
  7. extractionfollowed by extraction with EtOAc (2×50 mL)
  8. washThe combined organics was washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe crude was then purified over silica gel (100-200 M, 1.60% MeOH-DCM)

출처 및 근거

ORD 기록
ord-2e2ed4fc00a24b279eea1c43b97242d6
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08299065B2

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