tert-Butyl isocyanate → N2-[(tert-butylamino)carbonyl]-N1-{(3aS,4R,6aR)-2-[3-(trifluoromethyl)benzyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide

HRID 2363521Notes

Reaction equation

HRID 2363521 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:4]=[C:5]([CH:24]=[CH:25][CH:26]=1)[CH2:6][N:7]1[CH2:11][C@H:10]2[C@H:12]([NH:15][C:16](=[O:23])[C@H:17]([CH2:19][CH:20]([CH3:22])[CH3:21])[NH2:18])[CH2:13][CH2:14][C@H:9]2[CH2:8]1.[N:29]([C:32]([CH3:35])([CH3:34])[CH3:33])=[C:30]=[O:31]>ClCCl>[C:32]([NH:29][C:30]([NH:18][C@H:17]([C:16]([NH:15][C@H:12]1[C@H:10]2[C@H:9]([CH2:8][N:7]([CH2:6][C:5]3[CH:24]=[CH:25][CH:26]=[C:3]([C:2]([F:27])([F:1])[F:28])[CH:4]=3)[CH2:11]2)[CH2:14][CH2:13]1)=[O:23])[CH2:19][CH:20]([CH3:21])[CH3:22])=[O:31])([CH3:35])([CH3:34])[CH3:33]

Participants

4

Reactant 2

HCID 62412tert-Butyl isocyanateHCID 66590662N1-{(3aS,4R,6aR)-2-[3-(trifluoromethyl)benzyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide

Product 1

HCID 66590624N2-[(tert-butylamino)carbonyl]-N1-{(3aS,4R,6aR)-2-[3-(trifluoromethyl)benzyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To N1-{(3aS,4R,6aR)-2-[3-(trifluoromethyl)benzyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide (113 mg, 0.284 mmol) from Example 170 Step B in dichloromethane (0.5 mL) was added 2-isocyanato-2-methylpropane (35.1 μL, 0.313 mmol) and the reaction mixture was stirred at room temperature overnight. The reaction was reduced in volume and loaded onto a silica gel cartridge (Analogix®, Burlington, Wis., RS-12). The title compound was eluted with a gradient of 0% to 10% methanol (2 N ammonia)/dichloromethane over 20 minutes: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.74 (d, J=8.3, 1H), 7.73 (s, 1H), 7.57 (d, J=9.5, 2H), 7.44 (t, J=7.7, 1H), 6.56 (d, J=8.6, 1H), 6.33 (s, 1H), 4.88 (td, J=5.6, 8.9, 1H), 4.41-4.33 (m, 1H), 3.56 (d, J=13.5, 1H), 3.41 (d, J=13.6, 1H), 2.71 (dd, J=1.7, 9.2, 1H), 2.55-2.45 (m, 2H), 2.35 (dd, J=6.9, 8.9, 1H), 2.29-2.20 (m, 2H), 2.11 (dq, J=6.1, 12.1, 1H), 1.92-1.77 (m, 3H), 1.73-1.64 (m, 2H), 1.44 (s, 9H), 1.43-1.35 (m, 1H), 0.85 (d, J=3.3, 3H), 0.84 (d, J=3.2, 3H); MS (ESI+) m/z 497 (M+H)+.

Workup

  1. washThe title compound was eluted with a gradient of 0% to 10% methanol (2 N ammonia)/dichloromethane over 20 minutes

Sources & evidence

ORD record
ord-726f2bfd424d4acc8abcfda005e052d7
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

Loading…