2-Aminopropanol → 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid (2-hydroxy-1-methylethyl)amide

HRID 2068891Notes

Reaction equation

HRID 2068891 reaction equation
[CH3:1][C:2]1([CH3:39])[CH2:10][C:9]2[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:7]=[C:6]([C:19]3[N:20]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:21]4[C:26]([CH:27]=3)=[CH:25][CH:24]=[C:23]([C:28](O)=[O:29])[CH:22]=4)[C:5]=2[CH2:4][CH2:3]1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[NH2:63][CH:64]([CH3:67])[CH2:65][OH:66]>CN(C)C=O.C(OCC)(=O)C.O>[OH:66][CH2:65][CH:64]([NH:63][C:28]([C:23]1[CH:22]=[C:21]2[C:26]([CH:27]=[C:19]([C:6]3[C:5]4[CH2:4][CH2:3][C:2]([CH3:39])([CH3:1])[CH2:10][C:9]=4[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:17])([CH3:16])[CH3:18])[N:7]=3)[N:20]2[CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:36])([CH3:38])[CH3:37])=[CH:25][CH:24]=1)=[O:29])[CH3:67]

Participants

8

Reactant 4

HCID 51262-AminopropanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 585502432-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid

Product 1

HCID 585501082-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid (2-hydroxy-1-methylethyl)amideYield 93%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-{6,6-dimethyl-1-[2-(trimethylsilyl)ethoxymethyl]-4,5,6,7-tetrahydro-1H-indazol-3-yl}-1-[2-(trimethylsilyl)ethoxymethyl]-1H-indole-6-carboxylic acid obtained in Example 1, Step 4 (500 mg, 0.88 mmol) in N,N-dimethylformamide (5 ml) were added 1-hydroxybenzotriazole monohydrate (161 mg, 1.1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (202 mg, 1.1 mmol) and 2-amino-1-propanol (84 mg, 1.1 mmol) at room temperature, and the mixture was stirred at room temperature for 7 hr. To the reaction mixture were added water and ethyl acetate, and the organic layer was separated. Then, the organic layer was washed successively with water and saturated brine, and dried over sodium sulfate. Sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography to give the title compound (511 mg, yield 93%).

Workup

  1. customthe organic layer was separated
  2. washThen, the organic layer was washed successively with water and saturated brine
  3. dry with materialdried over sodium sulfate
  4. customSodium sulfate was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-311c3287b1134570873db2188d8b449c
Source dataset
uspto-grants-2012_10
Patent number
US08299070B2

Reaction notes

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