Diisopropylethylamine → HCID 58117227, compound

HRID 1406400Notes

Reaction equation

HRID 1406400 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17][N:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:31]1[C:32](=[O:48])[N:33]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[CH:34]=[C:35]([C:37](O)=[O:38])[CH:36]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:49]([NH:56][C:57]1[CH:58]=[N:59]NC=1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.O.O[N:64]1[C:68]2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17][N:18]3[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:28])[CH3:29])=[O:25])[CH2:22][CH2:23]3)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:31]1[C:32](=[O:48])[N:33]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:45])([CH3:47])[CH3:46])[CH:34]=[C:35]([C:37](=[O:38])[NH:59][C:58]2[CH:68]=[N:64][N:56]([CH2:49][C:50]3[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=3)[CH:57]=2)[CH:36]=1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 20785096HCID 20785096, compoundHCID 58117280HCID 58117280, compound2×

Product 1

HCID 58117227HCID 58117227, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

Intermediate (4c), 5-(4-tert-butoxycarbonyl-piperazin-1-ylmethyl)-2-[5-carboxy-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]indole-1-carboxylic acid tert-butyl ester, (1 g, 1.46 mmol), benzyl-1H-pyrazole-4-yl amine (0.75 g, 4.39 mmol), 1-hydroxybenzotriazole hydrate (0.59 g, 4.39 mmol) and tetrahydrofuran (15 mL) were placed in a microwave vial. To this solution was added N,N-diisopropylethylamine (0.58 g, 0.78 mL, 4.49 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.84 g, 4.39 mmol), the vial capped and heated in the microwave at 90° C. for 30 minutes. After cooling, the mixture was concentrated in vacuo and the residue partitioned between water and dichloromethane. The organic layer was separated and the aqueous was extracted with a further portion of dichloromethane. The combined dichloromethane layers were dried (Na2SO4) and concentrated in vacuo. The resultant crude product was purified by flash chromatography on SiO2 eluting with dichloromethane—15% methanol/dichloromethane (gradient) to afford the desired title compound as a yellow foam, 1.0 g, 82%.

Workup

  1. customthe vial capped
  2. temperatureAfter cooling
  3. concentrationthe mixture was concentrated in vacuo
  4. customthe residue partitioned between water and dichloromethane
  5. customThe organic layer was separated
  6. extractionthe aqueous was extracted with a further portion of dichloromethane
  7. dry with materialThe combined dichloromethane layers were dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resultant crude product was purified by flash chromatography on SiO2 eluting with dichloromethane—15% methanol/dichloromethane (gradient)

Sources & evidence

ORD record
ord-90f472c141ec4de8ac81ec110b52294b
Source dataset
uspto-grants-2014_12
Patent number
US08916591B2

Reaction notes

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