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Sodium Carbonate → 2-(cis-2,6-Dimethyl-morpholin-4-yl)-5-(2,6-dimethyl-pyridin-4-yl)-thiazole-4-carbonitrile

HRID 473977
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HRID 473977 반응식
Br[C:2]1[S:6][C:5]([N:7]2[CH2:12][C@H:11]([CH3:13])[O:10][C@H:9]([CH3:14])[CH2:8]2)=[N:4][C:3]=1[C:15]#[N:16].[CH3:17][C:18]1[CH:23]=[C:22](B(O)O)[CH:21]=[C:20]([CH3:27])[N:19]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.O.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>[CH3:14][C@H:9]1[O:10][C@@H:11]([CH3:13])[CH2:12][N:7]([C:5]2[S:6][C:2]([C:22]3[CH:21]=[C:20]([CH3:27])[N:19]=[C:18]([CH3:17])[CH:23]=3)=[C:3]([C:15]#[N:16])[N:4]=2)[CH2:8]1
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참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 23546910(2,6-Dimethylpyridin-4-yl)boronic acidHCID 672167795-Bromo-2-(cis-2,6-dimethyl-morpholin-4-yl)-thiazole-4-carbonitrile

생성물 1

HCID 672165242-(cis-2,6-Dimethyl-morpholin-4-yl)-5-(2,6-dimethyl-pyridin-4-yl)-thiazole-4-carbonitrile수율 85%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매
HCID 19096565Water ethanol용매

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온도
130 °C

실험 절차

A mixture of Intermediate 3 (20 g, 66.18 mmol), 2,6-dimethylpyridine-4-boronic acid, pinacol ester ([325142-95-8], 20 g, 85.79 mmol), tetrakis(triphenylphosphine)palladium (4.59 g, 3.97 mmol), 1,4-dioxane (120 mL), sodium carbonate (21.04 g, 198.55 mmol) in ethanol/water 1/1 (120 mL) was stirred and heated under nitrogen atmosphere at 130° C. for 6 h. The solvent was evaporated. The residue was taken up in DCM and washed twice with water. The organic layer was separated, dried with MgSO4 and evaporated. The residue was purified by column chromatography on silica gel (eluent gradient from 100% DCM to 98/2 DCM/MeOH). The desired fractions were collected and evaporated. The resulting residue was recrystallized from DIPE/CH3CN, yielding 18.5 g (85%) of Intermediate 4, after drying overnight under vacuum at 50° C.

후처리

  1. customThe solvent was evaporated
  2. washwashed twice with water
  3. customThe organic layer was separated
  4. dry with materialdried with MgSO4
  5. customevaporated
  6. customThe residue was purified by column chromatography on silica gel (eluent gradient from 100% DCM to 98/2 DCM/MeOH)
  7. customThe desired fractions were collected
  8. customevaporated
  9. customThe resulting residue was recrystallized from DIPE/CH3CN

출처 및 근거

ORD 기록
ord-f365e2cdb89142419e38feabb3eed020
출처 데이터셋
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08637510B2

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