Potassium Phosphate, Tribasic → [3,5-Dichloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-phenyl]-carbamic acid tert-butyl ester

HRID 2366246ノート

反応式

HRID 2366246 の反応式
[Cl:1][C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([Cl:17])=[CH:15][C:14](I)=[CH:13][C:12]=3[Cl:19])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[C:20]([O:24][C:25](=[O:27])[NH2:26])([CH3:23])([CH3:22])[CH3:21].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:20]([O:24][C:25](=[O:27])[NH:26][C:14]1[CH:15]=[C:16]([Cl:17])[C:11]([C:9]2[S:8][C:7]3[C:2]([Cl:1])=[N:3][CH:4]=[CH:5][C:6]=3[N:10]=2)=[C:12]([Cl:19])[CH:13]=1)([CH3:23])([CH3:22])[CH3:21]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866689974-Chloro-2-(2,6-dichloro-4-iodophenyl)thiazolo[5,4-c]pyridine

生成物 1

HCID 86669003[3,5-Dichloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-phenyl]-carbamic acid tert-butyl ester収率 90.3%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
85 °C

実験手順

A mixture of 4-chloro-2-(2,6-dichloro-4-iodophenyl)thiazolo[5,4-c]pyridine (0.40 g, 0.905 mmol), carbamic acid tert-butyl ester (0.159 g, 1.36 mmol), XantPhos (0.053 g, 0.091 mmol) and K3PO4 (0.384 g, 1.81 mmol) in toluene (9 mL) and water (1.5 mL), was degassed with a stream of argon. Pd2(dba)3 (0.041 g, 0.045 mmol) was then added and the reaction mixture was heated at 85° C. for 2 hours using microwave irradiation and then thermally at 100° C. for 18 hours. After cooling to room temperature, the crude residue was partitioned between water and EtOAc. The aqueous phase was further extracted with EtOAc (×2) and the combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-10% EtOAc in cyclohexane to afford the title compound as an off-white solid (0.352 g, 90% yield). LCMS (Method D): RT=4.68 min, m/z: 430 [M+H+].

後処理

  1. customwas degassed with a stream of argon
  2. custommicrowave irradiation
  3. temperatureAfter cooling to room temperature
  4. customthe crude residue was partitioned between water and EtOAc
  5. extractionThe aqueous phase was further extracted with EtOAc (×2)
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe resultant residue was purified by column chromatography on silica gel eluting with 0-10% EtOAc in cyclohexane

出典と根拠

ORDレコード
ord-edb96b26bf2e4bf79ebfb42e2c99fa20
出典データセット
uspto-grants-2014_04
特許番号
US08697708B2

反応ノート

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