Hydrochloric Acid → N-{2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl]-5-methoxy-6-(pyridin-4-ylamino)pyrimidin-4-yl}-2-methoxyacetamide

HRID 1482931노트

반응식

HRID 1482931 반응식
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]3[CH2:23][CH2:22][CH2:21][C:10]=3[N:11]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[F:20])[N:12]=2)[N:5]=[C:4]([NH:24][C:25](=[O:29])[CH2:26][O:27][CH3:28])[C:3]=1[O:30][CH3:31].Cl.Br[C:34]1[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CN(C=O)C.O.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[F:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH2:13][N:11]1[C:10]2[CH2:21][CH2:22][CH2:23][C:9]=2[C:8]([C:6]2[N:5]=[C:4]([NH:24][C:25](=[O:29])[CH2:26][O:27][CH3:28])[C:3]([O:30][CH3:31])=[C:2]([NH:1][C:34]3[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=3)[N:7]=2)=[N:12]1

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 881004-Bromopyridinium chlorideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 90015879N-{6-amino-2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazol-3-yl]-5-methoxypyrimidin-4-yl}-2-methoxyacetamide

생성물 1

HCID 72202406N-{2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl]-5-methoxy-6-(pyridin-4-ylamino)pyrimidin-4-yl}-2-methoxyacetamide

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
105 °C

실험 절차

50 mg of N-{6-amino-2-[1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]-pyrazol-3-yl]-5-methoxypyrimidin-4-yl}-2-methoxyacetamide 1-7-1 (0.12 mmol, 1.00 eq.), 25 mg of 4-bromopyridine hydrochloride (1:1) (0.13 mmol, 1.10 eq.), mg of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.02 mmol, 0.15 eq.), 115 mg of caesium carbonate (0.36 mmol, 3.00 eq.) and 2.6 mg of palladium diacetate (0.012 mmol, 0.1 eq.) were suspended in 0.5 mL of dry DMF and stirred under nitrogen atmosphere at 105° C. bath temperature for two h. The reaction mixture was diluted with water, the pH was adjusted to 7.5 using 4N aqueous hydrochloric acid and the crude product was extracted with DCM. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography yielding 29 mg (0.06 mmol, 49%) of analytically pure target compound.

후처리

  1. extractionthe crude product was extracted with DCM
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography
  5. customyielding 29 mg (0.06 mmol, 49%) of analytically pure target compound

출처 및 근거

ORD 기록
ord-21409567c7e1445694d895a847b23b7a
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09416125B2

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