Water → HCID 178502377, compound

HRID 1776013Notes

Reaction equation

HRID 1776013 reaction equation
C(OC([NH:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1)=O)C1C=CC=CC=1.[CH3:21][O:22][C:23](=[O:48])[NH:24][C@H:25]([C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[C:36]1[NH:37][CH:38]=[C:39]([C:41]2[CH:46]=[CH:45][C:44](Br)=[CH:43][CH:42]=2)[N:40]=1)=[O:30])[CH:26]([CH3:28])[CH3:27].CN(C)C=O.O.C(=O)(O)[O-].[Na+]>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.[OH-].[OH-].[Pd+2]>[CH3:21][O:22][C:23](=[O:48])[NH:24][C@H:25]([C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[C:36]1[NH:37][CH:38]=[C:39]([C:41]2[CH:42]=[CH:43][C:44]([C:15]3[CH:14]=[CH:13][C:12]([NH2:11])=[CH:17][CH:16]=3)=[CH:45][CH:46]=2)[N:40]=1)=[O:30])[CH:26]([CH3:28])[CH3:27]

Participants

9

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 27733224-(Benzyloxycarbonylamino)phenylboronic Acid (contains varying amounts of Anhydride)HCID 178502354HCID 178502354, compound

Product 1

HCID 178502377HCID 178502377, compoundYield 38.2%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 4-(benzyloxycarbonylamino)phenylboronic acid (1.57 g, 5.79 mmol) and ((S)-1-{(S)-2-[4-(4-bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (1.74 g, 3.86 mmol) in N,N-dimethylformamide (30 mL, 400 mmol) was added water (21.91 mL, 1216 mmol) and sodium bicarbonate (2.43 g, 28.96 mmol). The resulting mixture was purged with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (468 mg, 0.41 mmol) was added. The reaction mixture was purged with nitrogen and then heated at 90° C. overnight. The reaction mixture was cooled to RT, diluted with methanol (10 mL), then filtered. The filtrate was concentrated and the crude product was purified by preparative HPLC to give a white solid. (1.28 g) The crude material was dissolved in methanol (40 mL) and then pumped through a continuous flow hydrogenator at 70° C. using a palladium hydroxide on carbon (20% w/w) cartridge. The resulting solution was concentrated to ˜10 mL, treated with Stratospheres™ PL-CO3 resin and stirred at room temperature for 30 min. The reaction mixture was filtered and the filtrate was concentrated to give the title compound (680 mg).

Workup

  1. customThe resulting mixture was purged with nitrogen
  2. customThe reaction mixture was purged with nitrogen
  3. temperatureThe reaction mixture was cooled to RT
  4. additiondiluted with methanol (10 mL)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. customthe crude product was purified by preparative HPLC
  8. customto give a white solid
  9. custompumped through a continuous flow hydrogenator at 70° C.
  10. concentrationThe resulting solution was concentrated to ˜10 mL
  11. additiontreated with Stratospheres™ PL-CO3 resin
  12. filtrationThe reaction mixture was filtered
  13. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-e254abc3d15b415396423174325d9348
Source dataset
uspto-grants-2016_02
Patent number
US09260414B2

Reaction notes

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