4,5-Dimethyl-1,2-phenylenediamine → (2R,4R)-tert-butyl 2-((2-amino-4,5-dimethylphenyl)carbamoyl)-4-(3-(4-cyanophenyl)ureido)piperidine-1-carboxylate

HRID 1971308Notes

Reaction equation

HRID 1971308 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH2:10])[C:5]([NH2:9])=[CH:6][C:7]=1[CH3:8].[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][C@@H:21]([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[CH:30][CH:29]=2)=[O:26])[CH2:20][C@@H:19]1[C:36](O)=[O:37])=[O:17])([CH3:14])([CH3:13])[CH3:12].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C.O>[NH2:9][C:5]1[CH:6]=[C:7]([CH3:8])[C:2]([CH3:1])=[CH:3][C:4]=1[NH:10][C:36]([C@H:19]1[CH2:20][C@H:21]([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[CH:30][CH:29]=2)=[O:26])[CH2:22][CH2:23][N:18]1[C:16]([O:15][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:17])=[O:37]

Participants

7

Reactant 4

HCID 766354,5-Dimethyl-1,2-phenylenediamineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 57539001(2R,4R)-1-(tert-butoxycarbonyl)-4-(3-(4-cyanophenyl)ureido)piperidine-2-carboxylic Acid

Product 1

HCID 67266293(2R,4R)-tert-butyl 2-((2-amino-4,5-dimethylphenyl)carbamoyl)-4-(3-(4-cyanophenyl)ureido)piperidine-1-carboxylateYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4,5-dimethylbenzene-1,2-diamine (39 mg, 0.286 mmol) was added to a mixture of (2R,4R)-1-(tert-butoxycarbonyl)-4-(3-(4-cyanophenyl)ureido)piperidine-2-carboxylic acid (100 mg, 0.258 mmol), BOP (120 mg, 0.27 mmol) and DIEA (0.09 mL, 0.52 mmol) in DMF (1 mL), and the resulting solution was stirred at room temperature for 8 hours. Water (10 mL) was added to the reaction mixture and then extracted with ethyl acetate (2×20 mL). The organic layers were dried over MgSO4 and concentrated to give a red solid. Purification was done by Companion (ReadySep, 12 g, silica gel packed) with ethyl acetate/heptane from 50-80% to give the title compound as a white solid 104 mg (80%). LC-MS: 507.3, 505.4 (t=2.4 min).

Workup

  1. extractionextracted with ethyl acetate (2×20 mL)
  2. dry with materialThe organic layers were dried over MgSO4
  3. concentrationconcentrated
  4. customto give a red solid
  5. customPurification

Sources & evidence

ORD record
ord-be651246b08d4cf7b0a9333aaf07766b
Source dataset
uspto-grants-2013_04
Patent number
US08431597B2

Reaction notes

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