4-Methylmorpholine → 7-Bromo-4-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamide

HRID 2361369Notes

Reaction equation

HRID 2361369 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[C:14]([C:15]4[C:16]([CH3:34])=[C:17]([NH:21][CH2:22][C:23]5[CH:31]=CC(OC)=[CH:28][C:24]=5[C:25]([OH:27])=O)[CH:18]=[CH:19][CH:20]=4)=[CH:13][N:12]=[C:11]([C:35](=[O:37])[NH2:36])[C:7]=3[NH:8]2)=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1.[C:72]([O:75][CH2:76][CH3:77])(=O)C.CCCCCC>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[C:14]([C:15]4[CH:20]=[CH:19][CH:18]=[C:17]([N:21]5[CH2:22][C:23]6[C:24](=[CH:28][C:76]([O:75][CH3:72])=[CH:77][CH:31]=6)[C:25]5=[O:27])[C:16]=4[CH3:34])=[CH:13][N:12]=[C:11]([C:35]([NH2:36])=[O:37])[C:7]=3[NH:8]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 21226206Ethyl acetate hexaneHCID 679947572-((3-(7-Bromo-1-carbamoyl-9H-pyrido[3,4-b]indol-4-yl)-2-methylphenylamino)methyl)-5-methoxybenzoic acid

Product 1

HCID 679947687-Bromo-4-(3-(6-methoxy-1-oxoisoindolin-2-yl)-2-methylphenyl)-9H-pyrido[3,4-b]indole-1-carboxamideYield 78%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-((3-(7-bromo-1-carbamoyl-9H-pyrido[3,4-b]indol-4-yl)-2-methylphenylamino)methyl)-5-methoxybenzoic acid (0.425 g, the crude product from the previous step), BOP (1.008 g, 2.279 mmol), and N-methylmorpholine (0.752 mL, 6.84 mmol) in DMF (Volume: 5 mL) was stirred at 50° C. for 1 hr. The mixture was diluted with ethyl acetate (100 mL), washed with water (2×25 mL) and brine (25 mL), and dried over anhydrous MgSO4. The desired product (0.198 g, 78% yield over 2 steps), was isolated as a yellow solid by ISCO (40 g silica gel, solid loading, 40-80% ethyl acetate/hexane).

Workup

  1. washwashed with water (2×25 mL) and brine (25 mL)
  2. dry with materialdried over anhydrous MgSO4

Sources & evidence

ORD record
ord-32d9fc76dc99476ca8315394bf3bc8f2
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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