1-(difluoromethyl)-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → tert-Butyl (1S,2R)-2-(4-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

HRID 516059

反応式

HRID 516059 の反応式
Cl[C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4]([NH:24][C@@H:25]2[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]2[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[N:3]=1.[F:39][CH:40]([F:55])[N:41]1[CH:45]=[C:44](B2OC(C)(C)C(C)(C)O2)[CH:43]=[N:42]1>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:39][CH:40]([F:55])[N:41]1[CH:45]=[C:44]([C:2]2[C:7]3[C:8](=[O:22])[N:9]([CH2:11][C:12]4[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=4[O:20][CH3:21])[CH2:10][C:6]=3[C:5]([F:23])=[C:4]([NH:24][C@@H:25]3[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]3[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[N:3]=2)[CH:43]=[N:42]1

参加物

6

反応物 2

HCID 497579861-(difluoromethyl)-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86654712tert-Butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

生成物 1

HCID 86654725tert-Butyl (1S,2R)-2-(4-(1-(difluoromethyl)-1H-pyrazol-4-yl)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate収率 90%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 10340Sodium Carbonate溶媒HCID 312751,4-Dioxane溶媒

実験手順

A solution of tert-butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (35 mg, 0.064 mmol), 1-(difluoromethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (18.67 mg, 0.076 mmol) and bis(triphenylphosphine)palladium chloride (44.7 mg, 0.064 mmol) in dioxane (500 μL) and saturated aq Na2CO3 (500 μL) was heated at 85° C. for 2 h. After filtering out the solids, the solvent was removed and the residue was dissolved in MeOH and DCM and purified by preparative HPLC. The fractions were collected and ACN was removed via rotary evaporation. The resulting aq solution was neutralized with saturated aq NaHCO3, washed with EtOAc (2×200 mL), dried over Na2SO4, and filtered. The organic phase was stripped to dryness via rotary evaporation to yield the title compound (36 mg, 90%). [M+H] calc'd for C31H37F3N6O5, 631; found, 631.

後処理

  1. filtrationAfter filtering out the solids
  2. customthe solvent was removed
  3. dissolutionthe residue was dissolved in MeOH
  4. customDCM and purified by preparative HPLC
  5. customThe fractions were collected
  6. customACN was removed via rotary evaporation
  7. washwashed with EtOAc (2×200 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customThe organic phase was stripped to dryness via rotary evaporation

出典と根拠

ORDレコード
ord-fb4391d74b9f48bdacad5ae7a34b1e85
出典データセット
uspto-grants-2015_08
特許番号
US09108970B2

関連ノート

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