Hydrochloric Acid → HCID 66681748, compound

HRID 909550Notes

Reaction equation

HRID 909550 reaction equation
[N:1]1([C:5]([C:7]2[CH:33]=[CH:32][C:10]([O:11][C:12]3[CH:13]=[C:14]([C:24]4[NH:28][C:27]([C:29](O)=[O:30])=[CH:26][CH:25]=4)[CH:15]=[C:16]([O:18][C@@H:19]([CH3:23])[CH2:20][O:21][CH3:22])[CH:17]=3)=[C:9]([F:34])[CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.[NH2:35][CH2:36][C@H:37]([OH:39])[CH3:38].CCN=C=NCCCN(C)C.Cl.Cl>ClCCl.CN(C)C1C=CN=CC=1>[N:1]1([C:5]([C:7]2[CH:33]=[CH:32][C:10]([O:11][C:12]3[CH:13]=[C:14]([C:24]4[NH:28][C:27]([C:29]([NH:35][CH2:36][C@H:37]([OH:39])[CH3:38])=[O:30])=[CH:26][CH:25]=4)[CH:15]=[C:16]([O:18][C@@H:19]([CH3:23])[CH2:20][O:21][CH3:22])[CH:17]=3)=[C:9]([F:34])[CH:8]=2)=[O:6])[CH2:2][CH2:3][CH2:4]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 439938(2R)-1-aminopropan-2-olHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66680966HCID 66680966, compound

Product 1

HCID 66681748HCID 66681748, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

5-{3-[4-(Azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-1H-pyrrole-2-carboxylic acid (580 mg, 1.24 mmol) synthesized in Example (66g) was dissolved in dichloromethane (15 mL), and (R)-(−)-1-amino-2-propanol (196 μL, 2.48 mmol), WSCI•HCl (366 mg, 1.91 mmol) and 4-dimethylaminopyridine (228 mg, 1.87 mmol) were added, followed by stirring at room temperature for 18 hours under nitrogen atmosphere. To the reaction solution, 0.25N hydrochloric acid (100 mL) was added, and extraction was carried out with ethyl acetate (100 mL). The organic layer was washed with saturated brine, and subsequently dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: methanol/dichloromethane=3%-9%) to afford the desired compound (486 mg, yield 75%) as a white solid.

Workup

  1. extractionextraction
  2. washThe organic layer was washed with saturated brine
  3. dry with materialsubsequently dried over sodium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe resulting residue was purified
  6. washsilica gel column chromatography (elution solvent: methanol/dichloromethane=3%-9%)

Sources & evidence

ORD record
ord-ac85b5ac72fa493cbd171c684311c165
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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