Cesium carbonate → 3-{3-[2-[Tert-butoxycarbonylimino]-3-(3-{4-[2-(4-chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazin-1-yl}-benzyl)-2,3-dihydro-benzoimidazol-1-yl]-propoxy)-benzoic acid

HRID 410370ノート

反応式

HRID 410370 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:36]=[CH:37][CH:38]=1)[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]([CH2:15][CH2:16][CH2:17][O:18][C:19]2[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=2)[C:22]([OH:24])=[O:23])[C:7]1=[N:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[Cl:85][C:86]1[CH:91]=[CH:90][C:89]([C:92]2[CH2:97][CH2:96][C:95]([CH3:99])([CH3:98])[CH2:94][C:93]=2[CH2:100][N:101]2[CH2:106][CH2:105][NH:104][CH2:103][CH2:102]2)=[CH:88][CH:87]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:32]([O:31][C:29]([N:28]=[C:7]1[N:8]([CH2:15][CH2:16][CH2:17][O:18][C:19]2[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=2)[C:22]([OH:24])=[O:23])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N:6]1[CH2:5][C:4]1[CH:36]=[CH:37][CH:38]=[C:2]([N:104]2[CH2:103][CH2:102][N:101]([CH2:100][C:93]3[CH2:94][C:95]([CH3:99])([CH3:98])[CH2:96][CH2:97][C:92]=3[C:89]3[CH:90]=[CH:91][C:86]([Cl:85])=[CH:87][CH:88]=3)[CH2:106][CH2:105]2)[CH:3]=1)=[O:30])([CH3:34])([CH3:35])[CH3:33]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-2 回HCID 585649441-((4'-Chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazineHCID 674283863-(3-{3-(3-Bromo-benzyl)-2-[tert-butoxycarbonylimino]-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acid

生成物 1

HCID 674299233-{3-[2-[Tert-butoxycarbonylimino]-3-(3-{4-[2-(4-chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazin-1-yl}-benzyl)-2,3-dihydro-benzoimidazol-1-yl]-propoxy)-benzoic acid

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒2 回HCID 1140Toluene溶媒2 回

反応条件

温度
95 °C

実験手順

To a degassed solution of 3-(3-{3-(3-bromo-benzyl)-2-[tert-butoxycarbonylimino]-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acid (0.15 g, 0.25 mmol) in toluene (2 ml) at rt under nitrogen was added Pd(OAc)2 (5 mg, 0.12 mmol) and BINAP (30 mg, 0.048 mmol). Nitrogen was bubbled through the mixture for 10 min before a degassed solution of 1-[2-(4-chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazine (90 mg, 0.28 mmol) in toluene (1 ml) was introduced. After 5 min Cs2CO3 (0.84 g, 2.58 mmol) was added. During all additions nitrogen was continuously bubbled through the reaction. Once the additions were completed the reaction vessel was sealed and then heated to 95° C. where it was maintained for 3 h. After this time, the reaction was cooled to rt and additional Pd(OAc)2 (5 mg, 0.12 mmol) and BINAP (30 mg, 0.048 mmol) were introduced. The reaction was then heated to 95° C. where it was maintained for a further 2 h. After this time, the reaction was cooled to rt and filtered through Celite®. The collected solids were washed with dichloromethane and the combined filtrate and washings were concentrated under reduced pressure. The crude product 3-{3-[2-[tert-butoxycarbonylimino]-3-(3-{4-[2-(4-chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazin-1-yl}-benzyl)-2,3-dihydro-benzoimidazol-1-yl]-propoxy}-benzoic acid (290 mg) was used in the next step without further purification. HPLC-MS 818, 820 [M+1]+.

後処理

  1. additionwas introduced
  2. customDuring all additions nitrogen was continuously bubbled through the reaction
  3. customwas sealed
  4. temperaturewas maintained for 3 h
  5. temperatureAfter this time, the reaction was cooled to rt
  6. temperatureThe reaction was then heated to 95° C. where it
  7. temperaturewas maintained for a further 2 h
  8. temperatureAfter this time, the reaction was cooled to rt
  9. filtrationfiltered through Celite®
  10. washThe collected solids were washed with dichloromethane
  11. concentrationthe combined filtrate and washings were concentrated under reduced pressure
  12. customThe crude product 3-{3-[2-[tert-butoxycarbonylimino]-3-(3-{4-[2-(4-chloro-phenyl)-5,5-dimethyl-cyclohex-1-enylmethyl]-piperazin-1-yl}-benzyl)-2,3-dihydro-benzoimidazol-1-yl]-propoxy}-benzoic acid (290 mg) was used in the next step without further purification

出典と根拠

ORDレコード
ord-55239517c1a5441c99293ed54479d831
出典データセット
uspto-grants-2014_06
特許番号
US08759520B2

反応ノート

読み込み中…