Diisopropylethylamine → (3-{[(4-{[(tert-butoxycarbonyl)(methyl)amino]methyl}-tetrahydro-2H-pyran-4-yl)carbonyl]amino}propyl)(triphenyl)phosphonium bromide

HRID 58350Notes

Reaction equation

HRID 58350 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:10][C:11]1([C:17]([OH:19])=O)[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[Br-:52].[Br-].[NH3+:54][CH2:55][CH2:56][CH2:57][P+:58]([C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1)([C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1>CN(C)C=O.C(Cl)Cl>[Br-:52].[C:1]([O:5][C:6]([N:8]([CH2:10][C:11]1([C:17]([NH:54][CH2:55][CH2:56][CH2:57][P+:58]([C:71]2[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=2)([C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)[C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)=[O:19])[CH2:12][CH2:13][O:14][CH2:15][CH2:16]1)[CH3:9])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 894629104-{[(tert-butoxycarbonyl)(methyl)amino]methyl}tetrahydro-2H-pyran-4-carboxylic acidHCID 178419277HCID 178419277, compound

Product 1

HCID 89463008(3-{[(4-{[(tert-butoxycarbonyl)(methyl)amino]methyl}-tetrahydro-2H-pyran-4-yl)carbonyl]amino}propyl)(triphenyl)phosphonium bromide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

4-{[(tert-Butoxycarbonyl)(methyl)amino]methyl}tetrahydro-2H-pyran-4-carboxylic acid (549 mg, 2.01 mmol) was dissolved in N,N-dimethylformamide (5.5 mL). To this solution were added N,N-diisopropylethylamine (385 μL, 2.21 mmol), 1-hydroxybenzotriazole hydrate (323 mg, 2.11 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (578 mg, 3.01 mmol), and (3-ammoniopropyl)(triphenyl)phosphonium dibromide (1.16 g, 2.41 mmol). The reaction mixture was stirred overnight at room temperature, then diluted with methylene chloride and washed with 5% aqueous lithium chloride (3 times), 1N aqueous hydrogen chloride, and saturated sodium bicarbonate. The organic solution was dried over anhydrous sodium sulfate, filtered, and concentrated to give crude the title compound. The crude product was purified on a silica gel column eluting with 10% methanol with methylene chloride to isolate the title compound (729 mg, 55.4% yield).

Workup

  1. washwashed with 5% aqueous lithium chloride (3 times), 1N aqueous hydrogen chloride, and saturated sodium bicarbonate
  2. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-dfb1bfdac8d04bfcbbb05573a3ba2598
Source dataset
uspto-grants-2016_09
Patent number
US09434753B2

Reaction notes

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