Water → HCID 178451921, compound

HRID 1776019Notes

Reaction equation

HRID 1776019 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]1[NH:14][CH:15]=[C:16]([C:18]2[CH:23]=[CH:22][C:21](B3OC(C)(C)C(C)(C)O3)=[CH:20][CH:19]=2)[N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:34]1[CH:39]=[CH:38][C:37]([NH:40][C:41](=[O:59])[C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:53][CH2:52][N:51]([C:54]([CH:56]4[CH2:58][CH2:57]4)=[O:55])[CH2:50][CH2:49]3)=[CH:44][CH:43]=2)=[CH:36][CH:35]=1.CN(C)C=O.C(=O)(O)[O-].[Na+].O>CO.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:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]1[NH:14][CH:15]=[C:16]([C:18]2[CH:19]=[CH:20][C:21]([C:34]3[CH:35]=[CH:36][C:37]([NH:40][C:41](=[O:59])[C:42]4[CH:43]=[CH:44][C:45]([N:48]5[CH2:49][CH2:50][N:51]([C:54]([CH:56]6[CH2:57][CH2:58]6)=[O:55])[CH2:52][CH2:53]5)=[CH:46][CH:47]=4)=[CH:38][CH:39]=3)=[CH:22][CH:23]=2)[N:17]=1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 67495117HCID 67495117, compoundHCID 178451911HCID 178451911, compound

Product 1

HCID 178451921HCID 178451921, compoundYield 10.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of (S)-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (1.40 g, 3.19 mmol) and N-(4-bromo-phenyl)-4-(4-cyclopropanecarbonyl-piperazin-1-yl)-benzamide (0.910 g, 2.12 mmol) in N,N-dimethylformamide (16.53 mL, 213.5 mmol) at RT was added sodium bicarbonate (1.338 g, 15.93 mmol). Water (12.06 mL, 669.2 mmol) was then added. Nitrogen was bubbled through the resulting mixture for 5 min and then tetrakis(triphenylphosphine)palladium(0) (0.258 g, 0.223 mmol) was added. The reaction mixture was heated at 90° C. under nitrogen overnight, cooled to RT, diluted with methanol (30.0 mL), and filtered. The filtrate was concentrated and dissolved in ethyl acetate (˜3 mL) and hexanes (2 mL) was slowly added to give a precipitate of crude product. This material was filtered to provide 150 mg of the product. The filtrate was concentrated and subjected to the same precipitation conditions to provide an additional 50 mg of product. This material was combined with the first precipitation crop and was used without further purification in the next step.

Workup

  1. customNitrogen was bubbled through the resulting mixture for 5 min
  2. temperaturecooled to RT
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. dissolutiondissolved in ethyl acetate (˜3 mL)
  6. additionhexanes (2 mL) was slowly added
  7. customto give a precipitate of crude product
  8. filtrationThis material was filtered

Sources & evidence

ORD record
ord-f96bc7e3c9604084a000cc0e9acfff85
Source dataset
uspto-grants-2016_02
Patent number
US09260414B2

Reaction notes

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