Trifluoroacetic acid → HCID 131735600, compound

HRID 527747Notes

Reaction equation

HRID 527747 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@@H:19]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:26][CH:25]=3)[C:20](O)=[O:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[CH3:55][Si:56]1([CH3:74])[CH2:60][C@@H:59]([C:61]([NH:63][C@H:64]2[C:73]3[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=3)[CH2:67][CH2:66][CH2:65]2)=[O:62])[NH:58][CH2:57]1.C(O)(C(F)(F)F)=O.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:20]([N:58]3[C@H:59]([C:61](=[O:62])[NH:63][C@H:64]4[C:73]5[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=5)[CH2:67][CH2:66][CH2:65]4)[CH2:60][Si:56]([CH3:74])([CH3:55])[CH2:57]3)=[O:21])[CH2:23][C:24]3[CH:25]=[CH:26][C:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:28][CH:29]=3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 21345475HCID 21345475, compoundHCID 89930895HCID 89930895, compound

Product 1

HCID 131735600HCID 131735600, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-(tert-butoxycarbonyl)phenyl)propanoic acid (0.14 g, 0.29 mmol) in DMF (1.5 mL) was added 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride (86 mg, 0.31 mmol) at rt followed by a solution of (R)-3,3-dimethyl-N—((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-1,3-azasilolidine-5-carboxamide, TFA (105 mg, 0.261 mmol) and DIEA (115 μL) in DMF (2 mL). After 2 h, the reaction mixture was directly purified by preparative HPLC to afford the title compound (165 mg, 83% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J=8.1 Hz, 2H), 7.75 (d, J=7.5 Hz, 2H), 7.52 (t, J=6.7 Hz, 2H), 7.39-7.06 (m, 10H), 6.51 (d, J=8.4 Hz, 1H), 5.76 (d, J=8.8 Hz, 1H), 5.18-5.00 (m, 3H), 4.38-4.30 (m, 1H), 4.25-4.10 (m, 1H), 3.18 (d, J=13.4 Hz, 1H), 3.08-3.00 (m, 1H), 2.85-2.71 (m, 4H), 2.10-2.02 (m, 1H), 1.91-1.81 (m, 3H), 1.56 (s, 9H), 1.33 (dd, J=14.9, 1.7 Hz, 1H), 1.06 (dd, J=14.7, 10.1 Hz, 1H), 0.46 (s, 3H), 0.29 (s, 3H); MS(ESI+) m/z 758.2 (M+H)+.

Workup

  1. customthe reaction mixture was directly purified by preparative HPLC

Sources & evidence

ORD record
ord-259cd506a26c477d97891e3ee63385af
Source dataset
uspto-grants-2016_05
Patent number
US09345740B2

Reaction notes

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