Ammonia → {3-[({1-[(Methylamino)methyl]cyclopropyl}carbonyl)amino]propyl}(triphenyl)phosphonium bromide

HRID 58347Notes

Reaction equation

HRID 58347 reaction equation
[Br-:1].C(O[C:7]([N:9]([CH2:11][C:12]1([C:15]([NH:17][CH2:18][CH2:19][CH2:20][P+:21]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:16])[CH2:14][CH2:13]1)C)=O)(C)(C)C.Cl.C(OCC)C.N>C(Cl)Cl.CO>[Br-:1].[CH3:7][NH:9][CH2:11][C:12]1([C:15]([NH:17][CH2:18][CH2:19][CH2:20][P+:21]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[O:16])[CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 313Hydrochloric Acid2×HCID 3283Diethyl Ether2×HCID 89462959(3-{[(1-{[(Tert-butoxycarbonyl)(methyl)amino]methyl}cyclopropyl)carbonyl]amino}-propyl)(triphenyl)phosphonium bromide

Product 1

HCID 89462762{3-[({1-[(Methylamino)methyl]cyclopropyl}carbonyl)amino]propyl}(triphenyl)phosphonium bromideYield 112.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

(3-{[(1-{[(tert-butoxycarbonyl)(methyl)amino]methyl}cyclopropyl)carbonyl]amino}-propyl)(triphenyl)phosphonium bromide (809 mg, 1.32 mmol) was dissolved in methylene chloride (4.0 mL) and methanol (0.4 mL). The solution at room temperature was treated with 2.0 M hydrogen chloride in diethyl ether (1.7 mL, 3.44 mmol). The mixture was stirred overnight at room temperature. To the incomplete reaction was added additional 2.0 M hydrogen chloride in diethyl ether (0.36 mL, 0.71 mmol). After 3 additional hours, the reaction mixture was cooled with an ice bath and treated with 7N ammonia in methanol (0.77 mL, 5.42 mmol). After 30 minutes, the slurry that resulted was filtered, and the solids were washed with methylene chloride. The filtrate was concentrated to give the title compound (760 mg, 110%, 85% pure). The product of step 4 was used crude in next step.

Workup

  1. customTo the incomplete reaction
  2. temperatureAfter 3 additional hours, the reaction mixture was cooled with an ice bath
  3. waitAfter 30 minutes
  4. customthe slurry that resulted
  5. filtrationwas filtered
  6. washthe solids were washed with methylene chloride
  7. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-7335751bbed7448a80aacd1750528d35
Source dataset
uspto-grants-2016_09
Patent number
US09434753B2

Reaction notes

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