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Sodium Carbonate → (2S)-Methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(2'-(but-3-en-1-yl)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

HRID 1400722
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HRID 1400722 반응식
[CH2:1]([N:4]1[CH2:9][CH2:8][O:7][C:6]2[CH:10]=[CH:11][C:12]([C:15]3[N:20]4[N:21]=[C:22]([C:24]5[CH:29]=[CH:28][CH:27]=[C:26](Br)[CH:25]=5)[CH:23]=[C:19]4[N:18]=[C:17]([CH3:31])[C:16]=3[C@H:32]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:33]([O:35][CH3:36])=[O:34])=[C:13]([Cl:14])[C:5]1=2)[CH:2]=[CH2:3].[CH2:42]([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=1B(O)O)[CH2:43][CH:44]=[CH2:45].C([O-])([O-])=O.[Na+].[Na+]>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>[CH2:1]([N:4]1[CH2:9][CH2:8][O:7][C:6]2[CH:10]=[CH:11][C:12]([C:15]3[N:20]4[N:21]=[C:22]([C:24]5[CH:25]=[C:26]([C:47]6[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=6[CH2:42][CH2:43][CH:44]=[CH2:45])[CH:27]=[CH:28][CH:29]=5)[CH:23]=[C:19]4[N:18]=[C:17]([CH3:31])[C:16]=3[C@H:32]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:33]([O:35][CH3:36])=[O:34])=[C:13]([Cl:14])[C:5]1=2)[CH:2]=[CH2:3]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

6

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HCID 10340Sodium CarbonateHCID 86710751(2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetateHCID 86710753(2-(But-3-en-1-yl)phenyl)boronic acid

생성물 1

HCID 86710772(2S)-Methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(2'-(but-3-en-1-yl)-[1,1'-biphenyl]-3-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate
수율 100%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

A solution of (2S)-methyl 2-(7-(4-allyl-5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-2-(3-bromophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.092 g, 0.143 mmol), (2-(but-3-en-1-yl)phenyl)boronic acid (0.050 g, 0.286 mmol) and 2.0 M aq. Na2CO3 (0.179 mL, 0.358 mmol) in DMF (4 mL) was sparged with nitrogen for 10 min, treated with Pd(Ph3P)4 (0.012 g, 10.01 μmol), sparged for 5 min, then heated (90° C.) for 5 h. The reaction was cooled, then diltued with EtOAc (20 mL) and washed with water (10 mL) and brine (10 mL). The organic layer was dried (Na2SO4), filtered, and concentrated and the residue was purified by biotage (Isco 4 g SiO2, 0% (5 CV), 0-60% (20 CV), 60% (5 CV), EtOAc in hexanes) to afford the desired product (0.099 g, 0.143 mmol, 100% yield). LCMS (M+H)=691.4.

후처리

  1. customsparged for 5 min
  2. temperatureThe reaction was cooled
  3. washwashed with water (10 mL) and brine (10 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue was purified by biotage (Isco 4 g SiO2, 0% (5 CV), 0-60% (20 CV), 60% (5 CV), EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-9571a63fadee4fce9f2e057d552531f4
출처 데이터셋
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08906929B2

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