Diisopropylethylamine → HCID 131734885, compound

HRID 919629Notes

Reaction equation

HRID 919629 reaction equation
[CH3:1][N:2]([C:10]1[C:11]2[CH:18]=[CH:17][N:16]([S:19]([C:22]3[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=3)(=[O:21])=[O:20])[C:12]=2[N:13]=[CH:14][N:15]=1)[CH:3]1[CH2:9][O:8][CH2:7][CH2:6][NH:5][CH2:4]1.[Cl:29][C:30]1[CH:31]=[C:32]([NH:37][CH2:38][C:39](O)=[O:40])[CH:33]=[C:34]([Cl:36])[CH:35]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.CCN(C(C)C)C(C)C>CN(C=O)C.O>[Cl:29][C:30]1[CH:31]=[C:32]([NH:37][CH2:38][C:39]([N:5]2[CH2:4][CH:3]([N:2]([CH3:1])[C:10]3[C:11]4[CH:18]=[CH:17][N:16]([S:19]([C:22]5[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=5)(=[O:21])=[O:20])[C:12]=4[N:13]=[CH:14][N:15]=3)[CH2:9][O:8][CH2:7][CH2:6]2)=[O:40])[CH:33]=[C:34]([Cl:36])[CH:35]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 13138167(3,5-Dichlorophenyl)glycineHCID 67517444HCID 67517444, compound2×

Product 1

HCID 131734885HCID 131734885, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of N-methyl-N-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,4-oxazepan-6-amine ((0.114 g (0.283 mmol) 107.5, (3,5-dichloro-phenylamino)-acetic acid (0.0685 g (0.311 mmol) 107.b, and 1-hydroxybenzotriazole hydrate (9 mg (0.057 mmol) were dissolved in DMF (4 mL). The resulting solution was treated with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (60 mg, 0.311 mmol) and DIEA (100 uL (0.566 mmol) and stirred at rt for 24 hr. The mixture was diluted with H2O and extracted with EtOAc (2×) and 1:1 EtOAc/THF (2×). The combined organics were washed with 10% citric acid and brine, dried over MgSO4, filtered, and concentrated, absorbing onto 3 g SiO2. Purification by flash column chromatography (ISCO 12 g SiO2, 40% EtOAc/hex then gradient to 100% EtOAc) afforded (2-(3,5-dichlorophenylamino)-1-(6-(methyl(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-1,4-oxazepan-4-yl)ethanone (0.179 g) 107.6 as a white solid. LCMS (ESI) m/z: 603.20 [M+H]+.

Workup

  1. extractionextracted with EtOAc (2×) and 1:1 EtOAc/THF (2×)
  2. washThe combined organics were washed with 10% citric acid and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customabsorbing onto 3 g SiO2
  7. customPurification by flash column chromatography (ISCO 12 g SiO2, 40% EtOAc/hex

Sources & evidence

ORD record
ord-83d892c7b2834b778c2d9ca982465209
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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