Ammonia → 3-Fluoro-4-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}benzamide

HRID 909505Notes

Reaction equation

HRID 909505 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][C:12]1[CH:17]=[C:16]([C:18]2[NH:19][C:20]([C:23]3[S:24][CH:25]=[CH:26][N:27]=3)=[CH:21][CH:22]=2)[CH:15]=[C:14]([O:28][C@@H:29]([CH3:33])[CH2:30][O:31][CH3:32])[CH:13]=1)[C:5]([OH:7])=O.N.CC[N:37]=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.O>ClCCl.O>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][C:12]1[CH:17]=[C:16]([C:18]2[NH:19][C:20]([C:23]3[S:24][CH:25]=[CH:26][N:27]=3)=[CH:21][CH:22]=2)[CH:15]=[C:14]([O:28][C@@H:29]([CH3:33])[CH2:30][O:31][CH3:32])[CH:13]=1)[C:5]([NH2:37])=[O:7]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 666824973-Fluoro-4-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}benzoic acid

Product 1

HCID 580655433-Fluoro-4-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}benzamideYield 28%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

3-Fluoro-4-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxyl}benzoic acid (40.0 mg, 0.163 mmol) synthesized in Example (44a) was dissolved in dichloromethane (5 mL), and 28% aqueous ammonia solution (0.50 mL), WSCI•HCl (19.6 mg, 0.102 mmol) and HOBt•H2O (13.1 mg, 0.086 mmol) were added, followed by stirring at room temperature for 7 hours under nitrogen atmosphere. To the reaction solution, water (10 mL) was added, and extraction was carried out with ethyl acetate (20 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: ethyl acetate/hexane=0%-75%) to afford the desired compound (11.3 mg, yield 28%) 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: ethyl acetate/hexane=0%-75%)

Sources & evidence

ORD record
ord-f05bc131aac6417c8912835afbd9d1d8
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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