Cyclopropylamine → N-Cyclopropyl-2-[2-(7-methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamide

HRID 1189026Notes

Reaction equation

HRID 1189026 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](O)=[O:19])[CH2:15][N:16]=1)=[CH:8]2.Cl.C(N=C=N[CH2:38][CH2:39][CH2:40][N:41](C)C)C.ON1C2C=CC=CC=2N=N1.C1(N)CC1>O.CN(C)C=O>[CH:40]1([NH:41][C:18](=[O:19])[CH2:17][CH:14]2[S:13][C:12]([C:9]3[NH:10][C:11]4[C:7]([CH:8]=3)=[CH:6][C:5]([O:21][C:22]3[CH:23]=[N:24][C:25]([S:28]([CH3:31])(=[O:29])=[O:30])=[CH:26][CH:27]=3)=[CH:4][C:3]=4[O:2][CH3:1])=[N:16][CH2:15]2)[CH2:38][CH2:39]1

Participants

7

Reactant 4

HCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 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 67118657N-Cyclopropyl-2-[2-(7-methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamideYield 69.1%

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 (200 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (120 mg), 1-hydroxybenzotriazole (90 mg) and N,N-dimethylformamide (3 mL) was stirred at room temperature for 30 min, and then cyclopropylamine (50 mg) was added to the mixture. The whole was stirred at room temperature for 15 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 residual crystals were washed with ethyl acetate-hexane and collected by filtration to give pale yellow crystals. The crystals were recrystallized from acetone-methanol to give the title compound (150 mg, 68%) as colorless prisms. MS 501 (MH+). mp 248-249° C.

Workup

  1. stirringThe whole was stirred at room temperature for 15 h
  2. extractionthe resultant was extracted with ethyl acetate
  3. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washThe residual crystals were washed with ethyl acetate-hexane
  8. filtrationcollected by filtration
  9. customto give pale yellow crystals
  10. customThe crystals were recrystallized from acetone-methanol

Sources & evidence

ORD record
ord-735bf635b3c74d59a33ff5bcd32d28b9
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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