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Cesium carbonate → Methyl 2-(2-chloropyrimidin-5-ylamino)-5-cyclopropylbenzoate

HRID 42004
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HRID 42004 반응식
[NH2:1][C:2]1[CH:11]=[CH:10][C:9]([CH:12]2[CH2:14][CH2:13]2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].Br[C:16]1[CH:17]=[N:18][C:19]([Cl:22])=[N:20][CH:21]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.O>[Cl:22][C:19]1[N:20]=[CH:21][C:16]([NH:1][C:2]2[CH:11]=[CH:10][C:9]([CH:12]3[CH2:14][CH2:13]3)=[CH:8][C:3]=2[C:4]([O:6][CH3:7])=[O:5])=[CH:17][N:18]=1
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참가 물질

9

반응물 4

HCID 10796Cesium carbonateHCID 6066655-Bromo-2-chloropyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 13052309Methyl 2-amino-5-cyclopropylbenzoate

생성물 1

HCID 86657256Methyl 2-(2-chloropyrimidin-5-ylamino)-5-cyclopropylbenzoate

시약·촉매·용매 4

HCID 9811564
Bis(dibenzylideneacetone)palladium
촉매
HCID 962Water용매
HCID 8857Ethyl Acetate용매
HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

In a schlenck tube, a mixture of methyl 2-amino-5-cyclopropylbenzoate (described in Intermediate 8 (step A) (26.15 mmol, 5 g), 5-bromo-2-chloropyrimidine (26.93 mmol, 5.21 g), Xantphos (1.07 mmol, 0.6 g), Pd2(dba)3 (1.07 mmol, 0.6 g) and Cs2CO3 (36.65 mmol, 11.9 g) in dioxane (210 ml) was heated at 100° C. overnight. Water and ethyl acetate were added to the reaction crude. The aqueous phase was extracted again with more ethyl acetate. The organic phase was washed with water and brine, dried, filtered and concentrated in vacuo. The crude mixture was purified by reverse chromatography (Water: MeOH/AcN 1:1 from 0% to 100%) affording 6 g (60% of yield) of the expected product.

후처리

  1. extractionThe aqueous phase was extracted again with more ethyl acetate
  2. washThe organic phase was washed with water and brine
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude mixture was purified by reverse chromatography (Water: MeOH/AcN 1:1 from 0% to 100%)
  7. customaffording

출처 및 근거

ORD 기록
ord-185bb4a960824d82a53d420aa849be0a
출처 데이터셋
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08536165B2

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