Water → HCID 178502442, compound

HRID 1504340Notes

Reaction equation

HRID 1504340 reaction equation
[CH3:1][O:2][C:3](=[O:37])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][C@@H:14]([CH3:16])[CH2:13][C@H:12]1[C:17]1[NH:18][CH:19]=[C:20]([C:22]2[CH:27]=[CH:26][C:25](B3OC(C)(C)C(C)(C)O3)=[CH:24][CH:23]=2)[N:21]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][N:48]([C:51]2[CH:56]=[CH:55][C:54]([C:57](=[O:72])[NH:58][C:59]3[CH:64]=[C:63]([O:65][C:66]([F:69])([F:68])[F:67])[C:62](Br)=[CH:61][C:60]=3[Cl:71])=[CH:53][N:52]=2)[C@H:47]([CH3:73])[CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39].O.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.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:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][N:48]([C:51]2[CH:56]=[CH:55][C:54]([C:57](=[O:72])[NH:58][C:59]3[C:60]([Cl:71])=[CH:61][C:62]([C:25]4[CH:26]=[CH:27][C:22]([C:20]5[N:21]=[C:17]([C@@H:12]6[CH2:13][C@H:14]([CH3:16])[CH2:15][N:11]6[C:9](=[O:10])[C@@H:5]([NH:4][C:3]([O:2][CH3:1])=[O:37])[CH:6]([CH3:8])[CH3:7])[NH:18][CH:19]=5)=[CH:23][CH:24]=4)=[C:63]([O:65][C:66]([F:69])([F:68])[F:67])[CH:64]=3)=[CH:53][N:52]=2)[C@H:47]([CH3:73])[CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 67494940(R)-4-[5-(4-bromo-2-chloro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-3-methyl-piperazine-1-carboxylic acid tert-butyl esterHCID 178502436HCID 178502436, compound

Product 1

HCID 178502442HCID 178502442, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of [(S)-2-methyl-1-((2S,4S)-4-methyl-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 (155 mg, 0.30 mmol) and (R)-4-[5-(4-bromo-2-chloro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (180 mg, 0.30 mmol, Preparation 1) dissolved in toluene (1.9 mL) and water (0.33 mL) was added potassium carbonate (210 mg, 1.52 mmol). The reaction mixture was sparged under nitrogen. Tetrakis(triphenylphosphine)palladium(0) (42 mg, 0.036 mmol) was added and the reaction mixture was sparged with nitrogen and heated at 100° C. overnight. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated to produce the title intermediate as a brownish solid. (m/z): [M+H]+ calcd for C44H52ClF3N8O, 897.36. found 897.

Workup

  1. customThe reaction mixture was sparged under nitrogen
  2. customthe reaction mixture was sparged with nitrogen
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-dd665b864c1e45fd86d4b2d6618abc97
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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