Tris(hydroxymethyl)aminomethane → HCID 178461736, compound

HRID 421664Notes

Reaction equation

HRID 421664 reaction equation
[NH2:1][C:2]1[C:3]([C:19]([NH2:21])=[O:20])=[CH:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[N:7]([CH2:14][C@@H:15]([NH2:17])[CH3:16])[C:6]=2[N:18]=1.C1CCC([N:28]=[C:29]=[N:30]C2CCCCC2)CC1.C(OC(NC(NC(OC(C)(C)C)=O)=S)=O)(C)(C)C.C(O)C(N)(CO)CO>C(Cl)Cl>[NH2:1][C:2]1[C:3]([C:19]([NH2:21])=[O:20])=[CH:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[N:7]([CH2:14][C@@H:15]([NH:17][C:29]([NH2:30])=[NH:28])[CH3:16])[C:6]=2[N:18]=1

Participants

6

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 10868DicyclohexylcarbodiimideHCID 5193990N,N'-Di-Boc-thioureaHCID 595136442-amino-9-[(2S)-2-aminopropyl]-9H-pyrido[2,3-b]indole-3-carboxamide

Product 1

HCID 178461736HCID 178461736, compoundYield 42.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-amino-9-[(2S)-2-aminopropyl]-9H-pyrido[2,3-b]indole-3-carboxamide (30, 100 mg, 0.350 mmol) in methylene chloride (3 mL) was added PL-DCC resin (394 mg, 0.575 mmol) and the mixture was stirred at room temperature for 15 min. N,N′-bis-tert-butoxycarbonylthiourea (112 mg, 0.406 mmol) was added and the reaction mixture was stirred at room temperature overnight. PS-trisamine resin (4.12 g, 3.6 mmol/g, 14.8 mmol) was subsequently added and the resulting mixture was stirred at room temperature overnight. The resins were removed by suction filtration and the filtrate was concentrated under reduced pressure. Purification of the crude material by reverse phase C-18 silica gel chromatography [0-70% acetonitrile in water (containing 0.1% TFA)] afforded 2-amino-9-((2S)-2-{[amino(imino)methyl]amino}propyl)-9H-pyrido[2,3-b]indole-3-carboxamide (71, 48 mg 26%). NH4OAc standard conditions. DAD Retention time=4.98 min. M+H=326.

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. stirringthe resulting mixture was stirred at room temperature overnight
  3. customThe resins were removed by suction filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customPurification of the crude material by reverse phase

Sources & evidence

ORD record
ord-a3e1af1dfa554d5ca8f8948de581da0e
Source dataset
uspto-grants-2012_01
Patent number
US08101604B2

Reaction notes

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