4-Methylmorpholine → 1-[(9-hydroxy-9H-fluoren-9-yl)carbonyl]-N-[2-(4H-1,2,4-triazol-4-yl)benzyl]-L-prolinamide

HRID 857736Notes

Reaction equation

HRID 857736 reaction equation
[OH:1][C:2]1([C:15]([N:17]2[CH2:24][CH2:23][CH2:22][C@H:18]2[C:19](O)=[O:20])=[O:16])[C:14]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.[N:25]1[N:26]=[CH:27][N:28]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH2:36][NH2:37])[CH:29]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C>[OH:1][C:2]1([C:15]([N:17]2[CH2:24][CH2:23][CH2:22][C@H:18]2[C:19]([NH:37][CH2:36][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[N:28]2[CH:29]=[N:25][N:26]=[CH:27]2)=[O:20])=[O:16])[C:14]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 113442862-(1,2,4-Triazol-4-yl)benzylamineHCID 590382169-hydroxy-9-fluorenylcarbonyl-L-proline

Product 1

HCID 587601251-[(9-hydroxy-9H-fluoren-9-yl)carbonyl]-N-[2-(4H-1,2,4-triazol-4-yl)benzyl]-L-prolinamideYield 71.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 1-[(9-hydroxy-9H-fluoren-9-yl)carbonyl]-L-proline (Example 16, Step B, 0.06 g, 0.19 mmol) in DMF (1 mL) was added 1-[2-(4H-1,2,4triazol-4-yl) phenyl]methanamine (Example 5, Step A, 0.05 g, 0.31 mmol), BOP Reagent (0.11 g, 0.24 mmol) and N-methylmorpholine to pH=8. The mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour, filtered and purified on a Gilson Preparative HPLC to give the solid 1-[(9-hydroxy-9H-fluoren-9-yl)carbonyl]-N-[2-(4H-1,2,4-triazol-4-yl)benzyl]-L-prolinamide (0.065 g, HPLC RT=2.77 min, Method A; LCMS m/z=480). 1H NMR (400 MHz, CDCl3): δ 8.75 (s, 2H), 7.67–7.64 (m, 3H), 7.62–7.52 (m, 1H), 7.44–7.37 (m, 2H), 7.35–7.29 (m, 3H), 7.23–719 (m, 1H), 7.15 (s, 1H), 7.04 (d, 1H), 4.55–4.53 (m, 1H), 4.31–4.11 (m, 2H), 2.34–2.26 (m, 1H), 2.24–1.95 (m, 1H), 1.72–1.55 (m, 2H), 1.46–1.43 (m, 1H).

Workup

  1. filtrationfiltered
  2. custompurified on a Gilson Preparative HPLC

Sources & evidence

ORD record
ord-5422e7a9368143b88c228040263cf0f9
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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