1-Hydroxybenzotriazole → HCID 66898554, compound

HRID 1189030Notes

Reaction equation

HRID 1189030 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:21][C:22]2[CH:23]=[N:24][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:26][CH:27]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([OH:20])=O)[CH2:15][N:16]=1)=[CH:8]2.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[NH2:54][CH2:55][C@@H:56]([OH:58])[CH3:57]>O.CN(C)C=O>[OH:58][C@@H:56]([CH3:57])[CH2:55][NH:54][C:18](=[O:20])[CH2:17][CH:14]1[S:13][C:12]([C:9]2[NH:10][C:11]3[C:7]([CH:8]=2)=[CH:6][C:5]([O:21][C:22]2[CH:23]=[N:24][C:25]([S:28]([CH3:31])(=[O:29])=[O:30])=[CH:26][CH:27]=2)=[CH:4][C:3]=3[O:2][CH3:1])=[N:16][CH2:15]1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7311736(S)-(+)-1-Aminopropan-2-olHCID 67118501[2-(7-Methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid

Product 1

HCID 66898554HCID 66898554, compoundYield 68.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of [2-(7-methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (300 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (190 mg), 1-hydroxybenzotriazole (130 mg), (2S)-1-aminopropan-2-ol (100 mg) and N,N-dimethylformamide (5 mL) was stirred at room temperature for 40 h. Water was added to the mixture and the resultant was extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and brine, dried (MgSO4), filtered, and concentrated in vacuo. The residue was washed with ethyl acetate-diethyl ether to give pale yellow crystals. The crystals were recrystallized from acetone-methanol to give the title compound (230 mg, 68%) as colorless prisms. MS 519 (MH+). mp 185-186° C.

Workup

  1. extractionthe resultant was extracted with ethyl acetate
  2. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. washThe residue was washed with ethyl acetate-diethyl ether
  7. customto give pale yellow crystals
  8. customThe crystals were recrystallized from acetone-methanol

Sources & evidence

ORD record
ord-cffdd0e698304d4c8569f025466e82d0
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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