Water → tert-butyl 3-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]-3-hydroxypiperidine-1-carboxylate

HRID 1972923노트

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HRID 1972923 반응식
[NH2:1][C:2]1[C:7]2=[C:8](Br)[CH:9]=[C:10]([C:11]3([OH:24])[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1.[CH2:26]([N:33]1[CH:41]=[C:40]2[C:35]([CH:36]=[C:37](B3OC(C)(C)C(C)(C)O3)[CH:38]=[CH:39]2)=[N:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C([O-])([O-])=O.[Na+].[Na+].O>CN(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>[NH2:1][C:2]1[C:7]2=[C:8]([C:37]3[CH:38]=[CH:39][C:40]4[C:35]([CH:36]=3)=[N:34][N:33]([CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:41]=4)[CH:9]=[C:10]([C:11]3([OH:24])[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 58529580Tert-butyl 3-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3-hydroxypiperidine-1-carboxylate

생성물 1

HCID 58529683tert-butyl 3-[4-amino-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]-3-hydroxypiperidine-1-carboxylate수율 71%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

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온도
110 °C

실험 절차

To a stirred, degassed mixture tert-butyl 3-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3-hydroxypiperidine-1-carboxylate (292 mg, 0.71 mmol), Intermediate C (355 mg, 1.06 mmol), Na2CO3 (225 mg, 2.13 mmol) and H2O (1 mL) in DMF (6 mL) was added tetrakis(triphenylphosphine)palladium(0) (82 mg, 0.071 mmol). The reaction was heated (110° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (50 mL) and H2O (50 mL). The layers were separated and the aqueous layer was further extracted with ethyl acetate (1×50 mL). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated to dryness. The crude material was purified via ISCO® chromatography using a gradient of 50 to 75% ethyl acetate in hexanes to afford 270 mg (71%) of the desired product, which contained trace impurities. ES-MS m/z 540.30 [M+H]+, HPLC RT (min) 2.91.

후처리

  1. temperaturecooled to rt
  2. customThe mixture was partitioned between ethyl acetate (50 mL) and H2O (50 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was further extracted with ethyl acetate (1×50 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated to dryness
  8. customThe crude material was purified via ISCO® chromatography

출처 및 근거

ORD 기록
ord-9885bba19b5c453383421d6f9b8e64e7
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431695B2

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