Morpholine → HCID 117840499, compound

HRID 714827Notes

Reaction equation

HRID 714827 reaction equation
[ClH:1].[C:2]([C@@:4]1([CH:28]2[CH2:30][CH2:29]2)[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[N:18][N:19]([C:21]([CH3:26])([CH3:25])[C:22]([OH:24])=O)[CH:20]=3)[N:10]=2)[C:5]1=[O:27])#[N:3].C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH:62]1[CH2:67][CH2:66][O:65][CH2:64][CH2:63]1>CN(C)C=O>[ClH:1].[CH:28]1([C@:4]2([C:2]#[N:3])[CH2:8][CH2:7][N:6]([C:9]3[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]4[CH:17]=[N:18][N:19]([C:21]([CH3:25])([CH3:26])[C:22]([N:62]5[CH2:67][CH2:66][O:65][CH2:64][CH2:63]5)=[O:24])[CH:20]=4)[N:10]=3)[C:5]2=[O:27])[CH2:30][CH2:29]1

Participants

7

Reactant 5

HCID 8083MorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 117840434HCID 117840434, compound

Product 1

HCID 117840499HCID 117840499, compoundYield 37.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(4-((4-((3S)-3-cyano-3-cyclopropyl-2-oxopyrrolidin-1-yl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanoic acid hydrochloride (80 mg) obtained in Example 108 in N,N-dimethylformamide (2.0 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (58 mg), 1-hydroxybenzotriazole monohydrate (57 mg), N,N-diisopropylethylamine (97 μL) and morpholine (19 mg), and the mixture was stirred overnight at room temperature. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate). To a solution of the residue (87 mg) in ethanol (3.0 mL) was added dropwise 1 M hydrochloric acid (0.19 mL), the mixture was stirred for 5 min, and the solvent was evaporated under reduced pressure. The residue was recrystallized (ethanol/diisopropyl ether) to give the title compound (35 mg).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate)
  3. additionTo a solution of the residue (87 mg) in ethanol (3.0 mL) was added dropwise 1 M hydrochloric acid (0.19 mL)
  4. stirringthe mixture was stirred for 5 min
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was recrystallized (ethanol/diisopropyl ether)

Sources & evidence

ORD record
ord-d4266e197eb74e108a71edef555c731a
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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