Potassium Phosphate, Tribasic → tert-butyl 4-(2-methoxy-4-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)phenyl)piperazine-1-carboxylate

HRID 2209190ノート

反応式

HRID 2209190 の反応式
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]([O:16][C@@H:17]([C@@H:19]2[CH2:23][C:22](=[O:24])[NH:21][CH2:20]2)[CH3:18])[C:10]2[S:14][CH:13]=[N:12][C:11]=2[CH:15]=1)(=O)=O.[CH3:27][O:28][C:29]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[CH:31][C:30]=1[N:44]1[CH2:49][CH2:48][N:47]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:46][CH2:45]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2].O>[CH3:27][O:28][C:29]1[CH:34]=[C:33]([C:7]2[CH:8]=[C:9]([O:16][C@@H:17]([C@@H:19]3[CH2:23][C:22](=[O:24])[NH:21][CH2:20]3)[CH3:18])[C:10]3[S:14][CH:13]=[N:12][C:11]=3[CH:15]=2)[CH:32]=[CH:31][C:30]=1[N:44]1[CH2:45][CH2:46][N:47]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:48][CH2:49]1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 89494488Tert-butyl 4-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylateHCID 1178434547-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl trifluoromethanesulfonate

生成物 1

HCID 117843499tert-butyl 4-(2-methoxy-4-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)phenyl)piperazine-1-carboxylate

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
65 °C

実験手順

7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl trifluoromethanesulfonate (4.04) (100.7 mg, 0.245 mmol), tert-butyl 4-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate 7.08 (144 mg, 0.344 mmol), Pd(OAc)2 (2.8 mg, 0.012 mmol), 2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (12 mg 0.025 mmol), and K3PO4 (155 mg, 0.73 mmol) were taken up in THF (3.6 mL) under Ar. Water (0.36 mL) was added and the resulting stirred mixture was heated to 65° C. After 1.25 h, the reaction mixture was cooled and was partitioned between EtOAc, water, and brine. The phases were separated, and the aqueous phase was extracted with EtOAc. The combined organic phase was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography to afford tert-butyl 4-(2-methoxy-4-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)phenyl)piperazine-1-carboxylate. LCMS-ESI+ (m/z): [M+H]+ calcd for C29H37N4O5S: 553.3; found: 552.8.

後処理

  1. temperaturethe reaction mixture was cooled
  2. customwas partitioned between EtOAc, water, and brine
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with EtOAc
  5. dry with materialThe combined organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-08e8bbac787b4d95a8e569b027abcabb
出典データセット
uspto-grants-2016_06
特許番号
US09376441B2

反応ノート

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