Potassium Phosphate, Tribasic → HCID 69675225, compound

HRID 1751470Notes

Reaction equation

HRID 1751470 reaction equation
[CH3:1][O:2][C:3](=[O:41])[NH:4][CH:5]([CH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1)[C:6](=[O:34])[N:7]1[CH:12]([C:13]2[NH:14][C:15]([C:18]3[CH:23]=[CH:22][C:21](B4OC(C)(C)C(C)(C)O4)=[CH:20][CH:19]=3)=[CH:16][N:17]=2)[CH:11]2[CH2:33][CH:8]1[CH2:9][CH2:10]2.[C:42]([O:46][C:47]([N:49]1[CH2:53][CH2:52][CH2:51][CH:50]1[C:54]1[NH:55][C:56]([C:59]2[CH:68]=[CH:67][C:66]3[C:61](=[CH:62][CH:63]=[C:64](Br)[CH:65]=3)[CH:60]=2)=[CH:57][N:58]=1)=[O:48])([CH3:45])([CH3:44])[CH3:43].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.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>[C:42]([O:46][C:47]([N:49]1[CH2:53][CH2:52][CH2:51][CH:50]1[C:54]1[NH:55][C:56]([C:59]2[CH:68]=[CH:67][C:66]3[C:61](=[CH:62][CH:63]=[C:64]([C:21]4[CH:22]=[CH:23][C:18]([C:15]5[NH:14][C:13]([CH:12]6[CH:11]7[CH2:33][CH:8]([CH2:9][CH2:10]7)[N:7]6[C:6](=[O:34])[CH:5]([NH:4][C:3]([O:2][CH3:1])=[O:41])[CH:35]6[CH2:36][CH2:37][O:38][CH2:39][CH2:40]6)=[N:17][CH:16]=5)=[CH:19][CH:20]=4)[CH:65]=3)[CH:60]=2)=[CH:57][N:58]=1)=[O:48])([CH3:45])([CH3:44])[CH3:43]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 58185449tert-butyl (2S)-2-[5-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl]pyrrolidine-1-carboxylateHCID 69675391HCID 69675391, compound

Product 1

HCID 69675225HCID 69675225, compoundYield 77.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of [2-Oxo-1-(tetrahydro-pyran-4-yl)-2-(3-{5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-2-azabicyclo[2.2.1]hept-2-yl)-ethyl]-carbamic acid methyl ester (0.24 g, 0.42 mmol) in DME (2.5 mL) was added 2-[5-(6-Bromo-naphthalen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.19 g, 0.43 mmol), Tetrakis(triphenylphosphine)Palladium (0.03 g, 0.02 mmol) and aqueous potassium phosphate (2 M, 0.65 mL, 1.3 mmol). The solution was degassed with argon for 15 min and heated to 80° C. for 18 h with stirring. The solution was cooled and concentrated. The crude oil was purified by column chromatography (SiO2, 30-100% EtOAc (10% MeOH) in Hexanes to 50% MeOH in EtOAc) to provide 2-(5-{6-[4-(2-{2-[2-Methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-2-azabicyclo[2.2.1]hept-3-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.26 g, 76%). LCMS-ESI+: calc'd for C46H53N7O6: 799.41 (M+); Found: 800.4 (M+H+).

Workup

  1. customThe solution was degassed with argon for 15 min
  2. temperatureThe solution was cooled
  3. concentrationconcentrated
  4. customThe crude oil was purified by column chromatography (SiO2, 30-100% EtOAc (10% MeOH) in Hexanes to 50% MeOH in EtOAc)

Sources & evidence

ORD record
ord-09c092adff8348dea34bd4f930b2ac46
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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