Sodium Carbonate → Tert-butyl 4-[4-[7-(7-chloro-1-oxo-isoindolin-2-yl)-5-trityl-pyrrolo[2,3-b]pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate

HRID 627805ノート

反応式

HRID 627805 の反応式
Br[C:2]1[N:3]=[C:4]2[C:10]([N:11]3[CH2:19][C:18]4[C:13](=[C:14]([Cl:20])[CH:15]=[CH:16][CH:17]=4)[C:12]3=[O:21])=[CH:9][N:8]([C:22]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:5]2=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:49]2[CH:54]=[CH:53][C:52]([S:55]([CH:58]3[CH2:63][CH2:62][N:61]([C:64]([O:66]C(C)(C)C)=[O:65])[CH2:60][CH2:59]3)(=[O:57])=[O:56])=[CH:51][CH:50]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[Cl:20][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:13]=1[C:12](=[O:21])[N:11]([C:10]1[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:49]4[CH:50]=[CH:51][C:52]([S:55]([CH:58]5[CH2:59][CH2:60][N:61]([C:64]([O:66][C:13]([CH3:18])([CH3:14])[CH3:12])=[O:65])[CH2:62][CH2:63]5)(=[O:56])=[O:57])=[CH:53][CH:54]=4)[N:3]=3)[N:8]([C:22]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:9]=1)[CH2:19]2

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 67481388tert-Butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxa-borolan-2-yl)phenylsulfonyl)piperidine-1-carboxylateHCID 866765082-(2-bromo-5-trityl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-7-chloroisoindolin-1-one

生成物 1

HCID 71143607Tert-butyl 4-[4-[7-(7-chloro-1-oxo-isoindolin-2-yl)-5-trityl-pyrrolo[2,3-b]pyrazin-2-yl]phenyl]sulfonylpiperidine-1-carboxylate

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

2-(2-bromo-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl)-7-chloro-isoindolin-1-one (150 mg, 0.2476 mmol), tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate (112 mg, 0.2476 mmol) and Na2CO3 (371 μL of a 2.0 M aqueous solution, 0.7428 mmol) combined in 1,4-dioxane (3 mL) under N2. Mixture de-gassed (×3 vacuum-N2 cycles) then Pd(PPh3)4 (14 mg, 0.01238 mmol) added. Reaction mixture de-gassed (×3 cycles) and stirred overnight at 110° C. Reaction cooled and partitioned between DCM and water. Aqueous phase extracted with DCM and combined organics dried and concentrated. Residue purified by chromatography (silica, 0-100% EtOAc-petroleum ether gradient elution). Title compound obtained as a yellow solid (186 mg, 88%), taken directly on to deprotection reaction; MS (ES+) 850.0.

後処理

  1. customMixture de-gassed (×3 vacuum-N2 cycles)
  2. customReaction mixture
  3. customde-gassed (×3 cycles)
  4. customReaction
  5. temperaturecooled
  6. custompartitioned between DCM and water
  7. extractionAqueous phase extracted with DCM
  8. customcombined organics dried
  9. concentrationconcentrated
  10. customResidue purified by chromatography (silica, 0-100% EtOAc-petroleum ether gradient elution)

出典と根拠

ORDレコード
ord-2cbdcdcbf5104f09b638600d61e3a216
出典データセット
uspto-grants-2016_04
特許番号
US09309250B2

反応ノート

読み込み中…