Water → HCID 178466961, compound

HRID 1776021Notes

Reaction equation

HRID 1776021 reaction equation
[CH3:1][O:2][C:3](=[O:36])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24](B3OC(C)(C)C(C)(C)O3)=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].C(O)(C(F)(F)F)=O.[C:44]([O:48][C:49]([N:51]1[CH2:56][CH2:55][N:54]([C:57]2[CH:62]=[CH:61][C:60]([C:63](=[O:75])[NH:64][C:65]3[CH:70]=[CH:69][C:68](Br)=[C:67]([O:72][CH2:73][CH3:74])[CH:66]=3)=[CH:59][N:58]=2)[C@H:53]([CH3:76])[CH2:52]1)=[O:50])([CH3:47])([CH3:46])[CH3:45].COCCOC.O.C(=O)(O)[O-].[Na+]>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:44]([O:48][C:49]([N:51]1[CH2:56][CH2:55][N:54]([C:57]2[CH:62]=[CH:61][C:60]([C:63](=[O:75])[NH:64][C:65]3[CH:70]=[CH:69][C:68]([C:24]4[CH:25]=[CH:26][C:21]([C:19]5[N:20]=[C:16]([C@@H:12]6[CH2:13][CH2:14][CH2:15][N:11]6[C:9](=[O:10])[C@@H:5]([NH:4][C:3]([O:2][CH3:1])=[O:36])[CH:6]([CH3:7])[CH3:8])[NH:17][CH:18]=5)=[CH:22][CH:23]=4)=[C:67]([O:72][CH2:73][CH3:74])[CH:66]=3)=[CH:59][N:58]=2)[C@H:53]([CH3:76])[CH2:52]1)=[O:50])([CH3:47])([CH3:46])[CH3:45]

Participants

8

Reactant 6

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 80711,2-DimethoxyethaneHCID 516892Sodium BicarbonateHCID 67495118(R)-4-[5-(4-bromo-3-ethoxy-phenylcarbamoyl)-pyridin-2-yl]-3-methyl-piperazine-1-carboxylic acid tert-butyl esterHCID 178502353HCID 178502353, compound

Product 1

HCID 178466961HCID 178466961, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
90 °C

Procedure

A mixture of [(S)-2-methyl-1-((S)-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (253 mg, 0.52 mmol) and the TFA salt of (R)-4-[5-(4-bromo-3-ethoxy-phenylcarbamoyl)-pyridin-2-yl]-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (324 mg, 0.52 mmol; Preparation 21) was dissolved in 1,2-dimethoxyethane (5.32 mL, 51.2 mmol) and water (0.92 mL, 51.2 mmol) and the mixture was sparged under nitrogen. Sodium bicarbonate (161 mg, 1.92 mmol) was added, followed by tetrakis(triphenylphosphine)palladium(0) (89 mg, 0.077 mmol). The reaction mixture was further sparged with nitrogen, sealed under nitrogen and heated at 90° C. overnight. The reaction mixture was extracted with ethyl acetate and water. The organic layer was dried over sodium sulfate, filtered and concentrated to produce the title intermediate as a brown oil. (m/z): [M+H]+ calcd for C44H56N8O7 809.43 found 809.6.

Workup

  1. customThe reaction mixture was further sparged with nitrogen
  2. customsealed under nitrogen
  3. extractionThe reaction mixture was extracted with ethyl acetate and water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-9a2fd11e8a5246bebac8c94da7c04f11
Source dataset
uspto-grants-2016_02
Patent number
US09260414B2

Reaction notes

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