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

HRID 2361277Notes

Reaction equation

HRID 2361277 reaction equation
[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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-4191b6e61dbc4e199cb443e86242e317
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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