Acetic Acid → 2,2-dicyclohexyl-N-[(3aS,4R,6aR)-2-(N,N-dimethyl-D-leucyl)octahydrocyclopenta[c]pyrrol-4-yl]acetamide

HRID 1092567Notes

Reaction equation

HRID 1092567 reaction equation
N[C@H:2]([CH2:29][CH:30]([CH3:32])[CH3:31])[C:3]([N:5]1[CH2:9][C@H:8]2[C@H:10]([NH:13][C:14](=[O:28])[CH:15]([CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:11][CH2:12][C@H:7]2[CH2:6]1)=[O:4].C=O.[C:35](O)(=O)C.[C:39]([BH3-])#[N:40]>ClCCl>[CH:22]1([CH:15]([CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)[C:14]([NH:13][C@H:10]2[C@H:8]3[C@H:7]([CH2:6][N:5]([C:3](=[O:4])[C@@H:2]([CH2:29][CH:30]([CH3:31])[CH3:32])[N:40]([CH3:39])[CH3:35])[CH2:9]3)[CH2:12][CH2:11]2)=[O:28])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 498716Cyano-borohydrideHCID 66590431N-((3aS,4R,6aR)-2-((R)-2-amino-4-methylpentanoyl)octahydrocyclopenta[c]pyrrol-4-yl)-2,2-dicyclohexylacetamide

Product 1

HCID 665910102,2-dicyclohexyl-N-[(3aS,4R,6aR)-2-(N,N-dimethyl-D-leucyl)octahydrocyclopenta[c]pyrrol-4-yl]acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To N-((3aS,4R,6aR)-2-((R)-2-amino-4-methylpentanoyl)octahydrocyclopenta[c]pyrrol-4-yl)-2,2-dicyclohexylacetamide (0.133 g, 0.298 mmol) from Step B was added formaldehyde (0.228 mL, 2.98 mmol) in dichloromethane (0.5 mL). Acetic acid (0.5 mL) was added. The reaction was stirred at room temperature for 30 minutes, PS-cyanoborohydride (0.255 g, 0.597 mmol) was then added, and the reaction mixture was stirred at room temperature overnight. The reaction was filtered, and the solvent was removed in vacuo. The crude material was purified on silica gel chromatography on a silica gel cartridge (Analogix®, Burlington, Wis., RS-12) eluting with 1-10% methanol (2 N ammonia)/dichloromethane to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.29 (dd, J=7.1, 15.9, 1H), 4.46-4.35 (m, 1H), 4.09-3.99 (m, 1H), 3.92-3.80 (m, 1H), 3.70 (dd, J=8.6, 12.4, 1H), 3.66-3.58 (m, 2H), 3.45 (dd, J=4.8, 9.1, 0.5H), 2.78-2.64 (m, 1H), 2.63-2.53 (m, 1H), 2.42 (s, 3H), 2.38 (s, 3H), 2.23-2.14 (m, 0.5H), 2.13-1.99 (m, 2H), 1.99-1.82 (m, 5H), 1.82-1.63 (m, 8H), 1.60 (d, J=14.0, 1H), 1.57-1.51 (m, 1H), 1.45 (ddd, J=8.6, 18.8, 29.3, 3H), 1.36-1.05 (m, 9H), 1.01 (d, J=6.6, 3H), 0.91 (dd, J=6.6, 19.9, 3H); MS (ESI+) m/z 474 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. filtrationThe reaction was filtered
  3. customthe solvent was removed in vacuo
  4. customThe crude material was purified on silica gel chromatography on a silica gel cartridge (Analogix®, Burlington, Wis., RS-12)
  5. washeluting with 1-10% methanol (2 N ammonia)/dichloromethane

Sources & evidence

ORD record
ord-c378324f44e84d368e6d60e00ee8c8f2
Source dataset
uspto-grants-2012_03
Patent number
US08129417B2

Reaction notes

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