O-Phenylenediamine → tert-butyl (2R,4R)-2-((2-aminophenyl)carbamoyl)-4-(3-(4-cyanophenyl)ureido)piperidine-1-carboxylate

HRID 1685477Notes

Reaction equation

HRID 1685477 reaction equation
[C:1]1([NH2:8])[C:2]([NH2:7])=[CH:3][CH:4]=[CH:5][CH:6]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][C@@H:19]([NH:22][C:23]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][CH:27]=2)=[O:24])[CH2:18][C@@H:17]1[C:34](O)=[O:35])=[O:15])([CH3:12])([CH3:11])[CH3:10].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>[NH2:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[NH:8][C:34]([C@H:17]1[CH2:18][C@H:19]([NH:22][C:23]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][CH:27]=2)=[O:24])[CH2:20][CH2:21][N:16]1[C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:15])=[O:35]

Participants

7

Reactant 4

HCID 7243O-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 57539066tert-butyl (2R,4R)-2-((2-aminophenyl)carbamoyl)-4-(3-(4-cyanophenyl)ureido)piperidine-1-carboxylateYield 98.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Benzene-1,2-diamine (365 mg, 3.38 mmol) was added to a mixture of (2R,4R)-1-(tert-butoxycarbonyl)-4-(3-(4-cyanophenyl)ureido)piperidine-2-carboxylic acid (1400 mg, 3.60 mmol), BOP (1600 mg, 3.6 mmol) and DIEA (1.2 mL, 6.9 mmol) in DMF (20 mL), and the resulting solution was stirred at room temperature for 8 hours. Water (100 mL) was added to the reaction mixture and it was then extracted with ethyl acetate (2×200 mL). The organic layers were dried over MgSO4 and concentrated to give a red solid. Further purification by Companion (ReadySep, 80 g, silica gel packed) using ethyl acetate/heptane from 50-80% as eluent provided the title compound as a white solid 1600 mg (93%). LC-MS: 479.1, 477.2 (t=2.3 min).

Workup

  1. extractionwas then extracted with ethyl acetate (2×200 mL)
  2. dry with materialThe organic layers were dried over MgSO4
  3. concentrationconcentrated
  4. customto give a red solid
  5. customFurther purification by Companion (ReadySep, 80 g, silica gel packed)

Sources & evidence

ORD record
ord-c3123e3873aa40c380e3a26b607522e4
Source dataset
uspto-grants-2012_04
Patent number
US08148401B2

Reaction notes

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