Potassium Phosphate, Tribasic → HCID 178495674, compound

HRID 1751611Notes

Reaction equation

HRID 1751611 reaction equation
[CH3:1][CH:2]([CH3:39])[C@H:3]([NH:34][C:35](=[O:38])[O:36][CH3:37])[C:4](=[O:33])[N:5]1[C@H:10]([C:11]2[NH:15][C:14]3[C:16]4[C:21]([CH:22]=[CH:23][C:13]=3[N:12]=2)=[CH:20][C:19](B2OC(C)(C)C(C)(C)O2)=[CH:18][CH:17]=4)[CH2:9][C@@H:8]2[C@H:6]1[CH2:7]2.Br[C:41]1[CH:42]=[C:43]2[C:66](=[CH:67][CH:68]=1)[C:47]1[NH:48][C:49]([C@@H:51]3[CH2:55][C@H:54]([CH2:56][O:57][CH3:58])[CH2:53][N:52]3[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[N:50][C:46]=1[CH:45]=[CH:44]2.[O-]P([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>[CH3:37][O:36][C:35]([NH:34][C@@H:3]([CH:2]([CH3:1])[CH3:39])[C:4]([N:5]1[C@H:10]([C:11]2[NH:15][C:14]3[C:16]4[C:21]([CH:22]=[CH:23][C:13]=3[N:12]=2)=[CH:20][C:19]([C:41]2[CH:42]=[C:43]3[C:66](=[CH:67][CH:68]=2)[C:47]2[NH:48][C:49]([C@@H:51]5[CH2:55][C@H:54]([CH2:56][O:57][CH3:58])[CH2:53][N:52]5[C:59]([O:61][C:62]([CH3:65])([CH3:63])[CH3:64])=[O:60])=[N:50][C:46]=2[CH:45]=[CH:44]3)=[CH:18][CH:17]=4)[CH2:9][C@@H:8]2[C@H:6]1[CH2:7]2)=[O:33])=[O:38]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 178495670HCID 178495670, compoundHCID 178502481HCID 178502481, compound

Product 1

HCID 178495674HCID 178495674, compoundYield 100.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of methyl (S)-3-methyl-1-oxo-1-((1R,3S,5R)-3-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-naphtho[1,2-d]imidazol-2-yl)-2-azabicyclo[3.1.0]hexan-2-yl)butan-2-ylcarbamate (0.60 g, 1.1 mmol) and (2S,4S)-tert-butyl 2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (0.46 g, 1.0 mmol) in DME (5 mL) was added Pd(PPh3)4 (0.08 g, 0.07 mmol) and K3PO4 (2M aqueous, 1.5 mL, 3.0 mmol). The resulting solution was degassed with argon for 5 min and heated to 80° C. (external temperature, oil bath) for 18 h. The reaction mixture was then cooled to room temperature and diluted with MeOH and CH2Cl2. The solution was washed with H2O and brine, and the aqueous layers were back extracted with CH2Cl2 and MeOH (˜10:1). The organic layers were combined and dried over Na2SO4 and concentrated. The crude oil was purified by silica gel chromatography (30 to 100% EtOAc (10% MeOH)/Hexanes to 80% MeOH/EtOAc) to provide (2S,4S)-tert-butyl 2-(2′-((1R,3S,5R)-2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H,1′H-7,7′-binaphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (0.79 g, 71%). LCMS-ESI+: calc'd for C45H51N7O6: 785.39 (M+); Found: 786.61 (M+H+).

Workup

  1. customThe resulting solution was degassed with argon for 5 min
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. additiondiluted with MeOH and CH2Cl2
  4. washThe solution was washed with H2O and brine
  5. extractionthe aqueous layers were back extracted with CH2Cl2 and MeOH (˜10:1)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude oil was purified by silica gel chromatography (30 to 100% EtOAc (10% MeOH)/Hexanes to 80% MeOH/EtOAc)

Sources & evidence

ORD record
ord-d75496a3785e4582b8bb8146b4a1f0ac
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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