Pivaloyl chloride → HCID 86641976, compound

HRID 1092545Notes

Reaction equation

HRID 1092545 reaction equation
[CH3:1][NH:2][C@H:3]([C:8]([NH:10][C@H:11]1[C@H:18]2[C@H:14]([CH2:15][N:16]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=3)[CH2:17]2)[CH2:13][CH2:12]1)=[O:9])[CH2:4][CH:5]([CH3:7])[CH3:6].C(N(CC)C(C)C)(C)C.[C:39](Cl)(=[O:44])[C:40]([CH3:43])([CH3:42])[CH3:41]>ClCCl>[CH3:41][C:40]([CH3:43])([CH3:42])[C:39]([N:2]([CH3:1])[C@H:3]([C:8]([NH:10][C@H:11]1[C@H:18]2[C@H:14]([CH2:15][N:16]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:27])[F:28])[CH:21]=3)[CH2:17]2)[CH2:13][CH2:12]1)=[O:9])[CH2:4][CH:5]([CH3:7])[CH3:6])=[O:44]

Participants

5

Reactant 3

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 66591069HCID 66591069, compound

Product 1

HCID 86641976HCID 86641976, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To N2-methyl-N1-{(3aS,4R,6aR)-2-[3-(trifluoromethyl)benzyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-leucinamide (38.9 mg, 0.095 mmol) from Example 166 in dichloromethane (0.5 mL) was added N,N-diisopropylethylamine (24.77 μL, 0.142 mmol) followed by pivaloyl chloride (12.79 μL, 0.104 mmol), and the resultant 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-4). The title compound was eluted with a gradient of 0% to 100% ethyl acetate/hexanes over 15 minutes: 1H NMR (500 MHz, pyridine-d5) δ ppm 7.81 (d, J=7.4, 1H), 7.74 (s, 1H), 7.60-7.55 (m, 2H), 7.43 (dd, J=6.6, 14.3, 1H), 5.45 (dd, J=7.0, 8.7, 1H), 4.35-4.29 (m, 1H), 3.57 (d, J=13.5, 1H), 3.44 (d, J=13.5, 1H), 3.13 (s, 3H), 2.73 (dd, J=2.6, 8.9, 1H), 2.53-2.45 (m, 1H), 2.41 (ddd, J=2.7, 8.3, 12.0, 1H), 2.37-2.32 (m, 1H), 2.29 (dd, J=3.0, 9.0, 1H), 2.26-2.21 (m, 1H), 2.05 (dq, J=6.0, 12.0, 1H), 1.86-1.80 (m, 3H), 1.55 (ddd, J=6.9, 12.8, 19.6, 2H), 1.41-1.31 (m, 1H), 1.30 (s, 9H), 0.88 (d, J=6.7, 3H), 0.82 (d, J=6.6, 3H); MS (ESI+) m/z 496 (M+H)+.

Workup

  1. customthe resultant reaction mixture
  2. washThe title compound was eluted with a gradient of 0% to 100% ethyl acetate/hexanes over 15 minutes

Sources & evidence

ORD record
ord-9430eec3a3f24df78bde27fa4fb0efd5
Source dataset
uspto-grants-2012_03
Patent number
US08129417B2

Reaction notes

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