Sodium Bicarbonate → HCID 178502336, compound

HRID 1625503Notes

Reaction equation

HRID 1625503 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[N:16]=[C:17]([C@@H:20]4[CH2:24][CH2:23][CH2:22][N:21]4[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[NH:18][CH:19]=3)=[CH:11][CH:10]=2)O1.I[C:34]1[CH:58]=[CH:57][C:37]2[NH:38][C:39]([C@@H:41]3[CH2:45][CH2:44][CH2:43][N:42]3[C:46](=[O:56])[C@@H:47]([NH:51][C:52](=[O:55])[O:53][CH3:54])[CH:48]([CH3:50])[CH3:49])=[N:40][C:36]=2[CH:35]=1.C(=O)(O)[O-].[Na+]>C(#N)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:54][O:53][C:52]([NH:51][C@@H:47]([CH:48]([CH3:50])[CH3:49])[C:46]([N:42]1[CH2:43][CH2:44][CH2:45][C@H:41]1[C:39]1[NH:38][C:37]2[CH:57]=[CH:58][C:34]([C:9]3[CH:10]=[CH:11][C:12]([C:15]4[N:16]=[C:17]([C@@H:20]5[CH2:24][CH2:23][CH2:22][N:21]5[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[NH:18][CH:19]=4)=[CH:13][CH:14]=3)=[CH:35][C:36]=2[N:40]=1)=[O:56])=[O:55]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 178451911HCID 178451911, compoundHCID 178502346HCID 178502346, compound

Product 1

HCID 178502336HCID 178502336, compoundYield 38.8%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of tert-butyl (2S)-2-[4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carboxylate (169 mg, 0.3847 mmol) (Ref. WO 2008/021923), methyl ((S)-1-((S)-2-(5-iodo-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate (180.9 mg, 0.3847 mmol) and Pd(dppf)Cl2—CH2Cl2 (47.13 mg, 0.05771 mmol) in acetonitrile (4 mL) in a sealed tube (25 mL) under nitrogen atmosphere is added aq. sodium bicarbonate (961.8 μL of 1 M, 0.9618 mmol). The resultant suspension is heated in oil bath at 100° C. for 16 hours, concentrated, diluted with water and CH2Cl2, organic solution is separated, aqueous solution is extracted with dichloromethane, combined extracts are washed with brine and dried (Na2SO4). Purification of the residue on 25+M biotage silica gel cartridge using MeOH-ethyl acetate (0:100 to 15:85) as eluent afforded tert-butyl (2S)-2-[4-[4-[2-[(2S)-1-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]pyrrolidin-2-yl]-1H-benzimidazol-5-yl]phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carboxylate (101 mg, 0.1491 mmol, 38.75%) as light brown solid.

Workup

  1. concentrationconcentrated
  2. additiondiluted with water and CH2Cl2, organic solution
  3. customis separated
  4. extractionaqueous solution is extracted with dichloromethane
  5. washare washed with brine
  6. dry with materialdried (Na2SO4)
  7. customPurification of the residue on 25+M biotage silica gel cartridge

Sources & evidence

ORD record
ord-3acca0e5e3bf45ff8016957b27119e26
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

Loading…