Acetic Acid → 2-((3-(1-Carbamoyl-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indol-4-yl)-2-methylphenylamino)methyl)-5-chlorobenzoic acid

HRID 2361277노트

반응식

HRID 2361277 반응식
[NH2:1][C:2]1[C:3]([CH3:29])=[C:4]([C:8]2[C:20]3[C:19]4[C:14](=[CH:15][C:16]([O:21][CH2:22][CH2:23][O:24][CH3:25])=[CH:17][CH:18]=4)[NH:13][C:12]=3[C:11]([C:26]([NH2:28])=[O:27])=[N:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:30][C:31]1[CH:32]=[CH:33][C:34]([CH:40]=O)=[C:35]([CH:39]=1)[C:36]([OH:38])=[O:37].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClC(Cl)C.O1CCCC1>[C:26]([C:11]1[C:12]2[NH:13][C:14]3[C:19]([C:20]=2[C:8]([C:4]2[C:3]([CH3:29])=[C:2]([NH:1][CH2:40][C:34]4[CH:33]=[CH:32][C:31]([Cl:30])=[CH:39][C:35]=4[C:36]([OH:38])=[O:37])[CH:7]=[CH:6][CH:5]=2)=[CH:9][N:10]=1)=[CH:18][CH:17]=[C:16]([O:21][CH2:22][CH2:23][O:24][CH3:25])[CH:15]=3)(=[O:27])[NH2:28]

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 71762095-Chloro-2-formylbenzoic acidHCID 679945404-(3-amino-2-methylphenyl)-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indole-1-carboxamide

생성물 1

HCID 679950002-((3-(1-Carbamoyl-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indol-4-yl)-2-methylphenylamino)methyl)-5-chlorobenzoic acid수율 36.7%

시약·촉매·용매 2

HCID 63651,1-Dichloroethane용매HCID 8028Tetrahydrofuran용매

실험 절차

A mixture of 4-(3-amino-2-methylphenyl)-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indole-1-carboxamide (60.0 mg, 0.154 mmol), 5-chloro-2-formylbenzoic acid (70.9 mg, 0.384 mmol), sodium triacetoxyborohydride (98 mg, 0.461 mmol), and acetic acid (0.018 mL, 0.307 mmol) in dichloroethane (3 mL) and tetrahydrofuran (2 mL) was stirred at room temperature for 16 hr and then quenched with water (3 mL). The resulting mixture was diluted with ethyl acetate (50 mL) and washed with water (25 mL). The aqueous solution was extracted with ethyl acetate (2×30 mL). The combined extract was washed with brine (25 mL) and dried over anhydrous MgSO4. The organic solution was concentrated under vacuum to dryness. The residue was dissolved with minimum amount of DMF, diluted with MeOH (3 mL), divided into 2 portions, and purified by prep. reverse phase HPLC. The correct fractions were combined, concentrated under vacuum, and lyophilized to afford the desired product (TFA salt) (38 mg, 0.056 mmol, 36.7% yield) as a white powder.

후처리

  1. customquenched with water (3 mL)
  2. additionThe resulting mixture was diluted with ethyl acetate (50 mL)
  3. washwashed with water (25 mL)
  4. extractionThe aqueous solution was extracted with ethyl acetate (2×30 mL)
  5. extractionThe combined extract
  6. washwas washed with brine (25 mL)
  7. dry with materialdried over anhydrous MgSO4
  8. concentrationThe organic solution was concentrated under vacuum to dryness
  9. dissolutionThe residue was dissolved with minimum amount of DMF
  10. additiondiluted with MeOH (3 mL)
  11. custompurified by prep
  12. concentrationconcentrated under vacuum

출처 및 근거

ORD 기록
ord-4191b6e61dbc4e199cb443e86242e317
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08685969B2

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