Hydrochloric Acid → HCID 58497420, compound

HRID 2175199Notes

Reaction equation

HRID 2175199 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[C:6]([CH3:11])[CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:12][N:13]2[C:21]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[N:15]([C@@H:22]([CH2:27][CH2:28][CH3:29])[CH2:23][C:24]([OH:26])=[O:25])[C:14]2=[O:30])=[CH:3]1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:43][C:44]([S:47]([NH2:50])(=[O:49])=[O:48])([CH3:46])[CH3:45].C1CCN2C(=NCCC2)CC1.Cl>C1COCC1.O>[NH4+:2].[OH-:25].[CH3:1][N:2]1[C:10]2[C:5](=[C:6]([CH3:11])[CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:12][N:13]2[C:21]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[N:15]([C@@H:22]([CH2:27][CH2:28][CH3:29])[CH2:23][C:24]([NH:50][S:47]([C:44]([CH3:46])([CH3:45])[CH3:43])(=[O:49])=[O:48])=[O:26])[C:14]2=[O:30])=[CH:3]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2757335tert-ButylsulfonamideHCID 58497399HCID 58497399, compound

Product 2

HCID 14923Ammonium HydroxideYield 1%HCID 58497420HCID 58497420, compoundYield 143.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

(S)-3-[1-(1,4-Dimethyl-1H-indol-3-ylmethyl)-2-oxo-1,2-dihydro-imidazo[4,5-b]pyridin-3-yl]-hexanoic acid (85 mg, 0.21 mmol) was dissolved in THF (1.0 mL) and CDI (76 mg, 0.47 mmol) was added at room temperature. The mixture was heated at 55° C. for 1 hour. After the mixture is cooled down to room temperature, 2-methyl-propane-2-sulfonic acid amide (57 mg, 0.42 mmol) was added and after 10 min, DBU (0.063 mL, 0.42 mmol) was added. The mixture was stirred for 16 hours at room temperature. Then 2.0 mL of 1.0 M HCl was added followed by 30 mL of water. The mixture is extracted with EtOAc (3×20 mL) and the organic layers were combined, dried and concentrated to give crude product. Purification first by flash column chromatography using 5% MeOH in CH2Cl2 then by preparative TLC (6% MeOH in CH2Cl2 with 1% concentrated NH4OH) afforded 79 mg (71%) of the title compound. LCMS, M++1, m/z: 526.13.

Workup

  1. temperatureAfter the mixture is cooled down to room temperature
  2. extractionThe mixture is extracted with EtOAc (3×20 mL)
  3. customdried
  4. concentrationconcentrated
  5. customto give crude product
  6. customPurification first by flash column chromatography

Sources & evidence

ORD record
ord-dcf7674d816b432e89cf24287f1c805b
Source dataset
uspto-grants-2015_06
Patent number
US09062056B2

Reaction notes

Loading…