Benzyl isocyanate → HCID 54669708, compound

HRID 1852012Notes

Reaction equation

HRID 1852012 reaction equation
C(O[C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C@@H:17]([NH:19][C:20]([C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][CH:30]=2)[N:27]([CH2:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]4[C:39]([C:44]([OH:46])=[O:45])=[CH:40][CH:41]=[CH:42][CH:43]=4)=[CH:34][CH:33]=2)[C:26]([CH3:47])=[C:25]3[CH3:48])=[O:21])[CH3:18])[CH2:13][CH2:12]1)=[O:10])C1C=CC=CC=1.C(C1C=CC=C([C:59]2[CH:64]=[CH:63][C:62]([CH2:65][N:66]3C4C(=CC(C(=O)N[C@H](C5CCNCC5)C)=CC=4)C(C)=C3C)=[CH:61][CH:60]=2)C=1C(O)=O)(C)(C)C.N1CCCCC1.C(N=C=O)C1C=CC=CC=1.C(N(C(C)C)CC)(C)C>CC(O)=O.C(O)(C(F)(F)F)=O.C(Cl)Cl.[Pd].CO.C(#N)C.O.C(Cl)Cl>[CH2:65]([NH:66][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([C@@H:17]([NH:19][C:20]([C:22]2[CH:23]=[C:24]3[C:28](=[CH:29][CH:30]=2)[N:27]([CH2:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]4[C:39]([C:44]([OH:46])=[O:45])=[CH:40][CH:41]=[CH:42][CH:43]=4)=[CH:34][CH:33]=2)[C:26]([CH3:47])=[C:25]3[CH3:48])=[O:21])[CH3:18])[CH2:15][CH2:16]1)=[O:10])[C:62]1[CH:63]=[CH:64][CH:59]=[CH:60][CH:61]=1

Participants

10

Reactant 4

HCID 76639Benzyl isocyanateHCID 81531DiisopropylethylamineHCID 54669705HCID 54669705, compoundHCID 131732457HCID 131732457, compound

Product 1

HCID 54669708HCID 54669708, compound

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalyst2×HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolventHCID 21864137Acetonitrile methanol waterSolvent

Procedure

The title compound was prepared from (S)-4′-((5-((1-(1-((benzyloxy)carbonyl)piperidin-4-yl)ethyl)carbamoyl)-2,3-dimethyl-1H-indol-1-yl)methyl)-[1,1′-biphenyl]-2-carboxylic-acid (0.175 g, 0.250 mmol) following palladium catalyzed hydrogenation (18 mg, 10% Pd/c) in AcOH (5 mL) and subsequent coupling of the resulting piperidine ((S)-tert-butyl-4′-((2,3-dimethyl-5-((1-(piperidin-4-yl)ethyl)carbamoyl)-1H-indol-1-yl)methyl)-[1,1′-biphenyl]-2-carboxylate) with benzyl isocyanate (6.8 mg, 0.049 mmol) in dicholoromethane (DCM) (1 mL)/di-isopropylethylamine (9.2 μL, 0.053 mmol) and then removal of t-butyl ester in TFA/DCM (1:1, 2 mL). Completion at each synthetic step was monitored by analytical HPLC and the title compound was isolated by reverse phase prep-HPLC (MeOH/Acetonitrile/water) ESI-MS (m/z): 642 [M+1]+.

Sources & evidence

ORD record
ord-4ca940fb529e410b8da889989c66bb0f
Source dataset
uspto-grants-2015_02
Patent number
US08957093B2

Reaction notes

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