Phenyl isocyanate → HCID 71226423, compound

HRID 2370020Notes

Reaction equation

HRID 2370020 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:16][CH2:15][CH2:14][CH:13]([NH:17][C@@H:18]3[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]3[NH2:24])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].CCN(CC)CC.[N:32]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[C:33]=[O:34]>C1COCC1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:16][CH2:15][CH2:14][C@H:13]([NH:17][C@@H:18]3[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]3[NH:24][C:33]([NH:32][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[O:34])[CH2:12][CH2:11]2)=[CH:8][CH:9]=1)([O-:3])=[O:2]

Participants

5

Reactant 3

HCID 7672Phenyl isocyanateHCID 8471TriethylamineHCID 71235678HCID 71235678, compound

Product 1

HCID 71226423HCID 71226423, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a round bottom flask was added (1R,2R)—N1-(1-(4-nitrophenyl)azepan-4-yl)cyclohexane-1,2-diamine (70 mg, 0.211 mmol), THF (3 mL), and Et3N (0.029 mL, 0.211 mmol). To the resulting solution was added isocyanatobenzene (25.08 mg, 0.211 mmol). The reaction was stirred at rt overnight. After this time, the reaction mixture was concentrated. The resulting crude product was purified by RP prep-HPLC to give a mixture of 2 diastereomers. The mixture of two diastereomers was separated by chiral HPLC (chiral separation method A) to give the desired product, 1-((1R,2R)-2-((S)-1-(4-nitrophenyl)azepan-4-ylamino)cyclohexyl)-3-phenylurea (7 mg, 0.019 mmol, 6.7% yield) as a yellow solid. Anal. Calcd. for C25H33N5O3 m/z 451.5, found: 452.3 (M+H)+; 1H NMR (500 MHz, CDCl3) δ ppm 8.10 (d, J=9.35 Hz, 2H), 7.30-7.27 (m, 2H), 7.22 (t, J=7.70 Hz, 2H), 6.99 (t, J=7.15 Hz, 1H), 6.60 (d, J=9.35 Hz, 2H), 4.57 (br. s., 1H), 3.66-3.53 (m, 2H), 3.53-3.45 (m, 1H), 3.44-3.35 (m, 1H), 3.21 (d, J=4.95 Hz, 1H), 2.85-2.73 (m, 1H), 2.24 (td, J=10.31, 3.57 Hz, 1H), 2.09 (d, J=9.35 Hz, 2H), 1.97 (d, J=12.10 Hz, 1H), 1.90 (d, J=11.55 Hz, 2H), 1.73 (d, J=9.90 Hz, 2H), 1.69-1.61 (m, 2H), 1.44-1.34 (m, 2H), 1.23-1.07 (m, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 157.11, 153.29, 139.21, 136.84, 129.12, 126.49, 123.13, 120.06, 110.01, 60.75, 56.99, 56.15, 49.50, 45.82, 34.95, 33.49, 33.29, 32.63, 25.06, 24.85, 23.76.

Workup

  1. concentrationAfter this time, the reaction mixture was concentrated
  2. customThe resulting crude product was purified by RP prep-HPLC
  3. customto give
  4. additiona mixture of 2 diastereomers
  5. additionThe mixture of two diastereomers
  6. customwas separated by chiral HPLC (chiral separation method A)

Sources & evidence

ORD record
ord-5cd2972f1ede463e85b08ea30d238ee3
Source dataset
uspto-grants-2014_04
Patent number
US08710049B2

Reaction notes

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