Diisopropylethylamine → 2-(5-{3-[4-(Azetidin-1-ylcarbonyl)-2-methylphenoxy]-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-1H-pyrrol-2-yl)-1,3-thiazole

HRID 1964584Notes

Reaction equation

HRID 1964584 reaction equation
[CH3:1][O:2][CH2:3][C@H:4]([CH3:33])[O:5][C:6]1[CH:7]=[C:8]([CH:20]=[C:21]([C:23]2[NH:24][C:25]([C:28]3[S:29][CH:30]=[CH:31][N:32]=3)=[CH:26][CH:27]=2)[CH:22]=1)[O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][C:11]=1[CH3:19].Cl.[NH:35]1[CH2:38][CH2:37][CH2:36]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>ClCCl>[N:35]1([C:14]([C:13]2[CH:17]=[CH:18][C:10]([O:9][C:8]3[CH:20]=[C:21]([C:23]4[NH:24][C:25]([C:28]5[S:29][CH:30]=[CH:31][N:32]=5)=[CH:26][CH:27]=4)[CH:22]=[C:6]([O:5][C@@H:4]([CH3:33])[CH2:3][O:2][CH3:1])[CH:7]=3)=[C:11]([CH3:19])[CH:12]=2)=[O:16])[CH2:38][CH2:37][CH2:36]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12308726Azetidine hydrochlorideHCID 666816654-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}-3-methylbenzoic acid

Product 1

HCID 580655352-(5-{3-[4-(Azetidin-1-ylcarbonyl)-2-methylphenoxy]-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-1H-pyrrol-2-yl)-1,3-thiazoleYield 92.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}-3-methylbenzoic acid (58 mg, 0.125 mmol) synthesized in Example (53a) and azetidine hydrochloride (29 mg, 0.310 mmol) were dissolved in dichloromethane (10.0 mL), and HATU (95 mg, 0.250 mmol) and N,N-diisopropylethylamine (0.15 mL, 0.861 mmol) were added, followed by stirring at room temperature overnight under nitrogen atmosphere. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=75%-90%) to afford the desired compound (58 mg, yield 92%) as a yellow solid.

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. customthe resulting residue was purified
  3. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=75%-90%)

Sources & evidence

ORD record
ord-300f63446ea4407a954149e08b759eee
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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