Triethylamine → HCID 178502199, compound

HRID 1185794Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:24])[CH:15]([NH:19][C:20]([O:22][CH3:23])=[O:21])[CH:16]([CH3:18])[CH3:17])[CH:10]([C:25]2[NH:26][CH:27]=[C:28]([C:30]3[CH:35]=[CH:34][C:33](Br)=[CH:32][CH:31]=3)[N:29]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:37][O:38][C:39](=[O:65])[NH:40][CH:41]([C:45]([N:47]1[CH2:51][CH2:50][CH2:49][CH:48]1[C:52]1[NH:53][C:54]([C:57]2[CH:62]=[CH:61][C:60]([C:63]#[CH:64])=[CH:59][CH:58]=2)=[CH:55][N:56]=1)=[O:46])[CH:42]([CH3:44])[CH3:43].C(N(CC)CC)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:24])[CH:15]([NH:19][C:20]([O:22][CH3:23])=[O:21])[CH:16]([CH3:18])[CH3:17])[CH:10]([C:25]2[NH:26][CH:27]=[C:28]([C:30]3[CH:35]=[CH:34][C:33]([C:64]#[C:63][C:60]4[CH:61]=[CH:62][C:57]([C:54]5[NH:53][C:52]([CH:48]6[CH2:49][CH2:50][CH2:51][N:47]6[C:45](=[O:46])[CH:41]([NH:40][C:39]([O:38][CH3:37])=[O:65])[CH:42]([CH3:44])[CH3:43])=[N:56][CH:55]=5)=[CH:58][CH:59]=4)=[CH:32][CH:31]=3)[N:29]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

3-[4-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-(2-methoxycarbonylamino-3-methyl-butyryl)-piperazine-1-carboxylic acid tert-butyl ester (600 mg, 1.06 mmol) was combined with (1-{2-[5-(4-Ethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (503 mg, 1.27 mmol) and Pd(PPh3)4 (122 mg, 0.106 mmol) under an argon atmosphere. DMF (degassed with Argon) was added followed by triethylamine (1.47 mL, 10.6 mmol) and copper(I) iodide (20.0 mg, 0.106 mmol). The mixture was heated at 80° C. After 20 minutes, volatiles were removed in vacuo and the crude material was semi-purified via chromatography on silica gel (eluent: EtOAc w MeOH 10%/hexanes) to yield the product 4-(2-Methoxycarbonylamino-3-methyl-butyryl)-3-{-4-[4-(4-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenylethynyl)-phenyl]-1H-imidazol-2-yl}-piperazine-1-carboxylic acid tert-butyl ester (542 mg). LCMS-ESI+: calc'd for C47H59N9O8: 878.0 (M+). Found: 878.5 (M+H+).

Workup

customvolatiles were removed in vacuo

Sources & evidence

ORD record: ord-fd61c0f630e0488faa6b538f1227a5f0
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669234B2

Reaction notes

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