Diisopropylethylamine → (S)-3-[(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-amino]-1,1-bis-[3-(3-{[(1-methyl-1H-imidazol-2-ylmethyl)-carbamoyl]-methoxy}-phenyl)-propyl]-piperidinium hydroxide

HRID 509910Notes

Reaction equation

HRID 509910 reaction equation
[Cl-].[C:2]([CH2:5][O:6][C:7]1[CH:8]=[C:9]([CH2:13][CH2:14][CH2:15][N+:16]2([CH2:34][CH2:35][CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH2:44][C:45]([OH:47])=O)[CH:38]=3)[CH2:21][CH2:20][CH2:19][C@H:18]([NH:22][C:23]([C:25]3[C:30]([NH2:31])=[N:29][C:28]([NH2:32])=[C:27]([Cl:33])[N:26]=3)=[O:24])[CH2:17]2)[CH:10]=[CH:11][CH:12]=1)([OH:4])=[O:3].[CH3:48][N:49]1[CH:53]=[CH:52][N:51]=[C:50]1[CH2:54][NH2:55].[CH:56]([N:59](CC)C(C)C)(C)C.F[B-](F)(F)F.N1(O[C:80]([N:84]([CH3:86])C)=[N+:81]([CH3:83])[CH3:82])C2C=CC=CC=2N=N1>CN(C)C=O>[OH-:3].[NH2:31][C:30]1[C:25]([C:23]([NH:22][C@H:18]2[CH2:19][CH2:20][CH2:21][N+:16]([CH2:34][CH2:35][CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([O:43][CH2:44][C:45](=[O:47])[NH:59][CH2:56][C:80]4[N:81]([CH3:82])[CH:83]=[CH:86][N:84]=4)[CH:38]=3)([CH2:15][CH2:14][CH2:13][C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([O:6][CH2:5][C:2](=[O:4])[NH:55][CH2:54][C:50]4[N:49]([CH3:48])[CH:53]=[CH:52][N:51]=4)[CH:8]=3)[CH2:17]2)=[O:24])=[N:26][C:27]([Cl:33])=[C:28]([NH2:32])[N:29]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 533842(1-methyl-1H-imidazol-2-yl)methanamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 117856257(S)-1,1-Bis-[3-(3-carboxymethoxy-phenyl)-propyl]-3-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-piperidinium chloride

Product 1

HCID 117856585(S)-3-[(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-amino]-1,1-bis-[3-(3-{[(1-methyl-1H-imidazol-2-ylmethyl)-carbamoyl]-methoxy}-phenyl)-propyl]-piperidinium hydroxide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-1,1-Bis-[3-(3-carboxymethoxy-phenyl)-propyl]-3-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)amino]-piperidinium chloride (100 mg, 0.13 mmol),), C-(1-Methyl-1H-imidazol-2-yl)-methylamine (53 mg, 0.29 mmol) and N,N-Diisopropylethylamine (225 μl, 1.3 mmol) are dissolved in N,N-dimethylformamide (3.5 ml), 2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (93 mg, 0.29 mmol) is added. The reaction is stirred at room temperature overnight and purified by preparative HPLC-MS (MeOH/H2O+0.1% TFA). The product is dissolved in dichloromethane, washed with a 2 molar potassiumcarbonate solution, dried over sodiumsulfate and concentrated in vacuo. LC (method L): tR=1.15 min; Mass spectrum (ESI+): m/z=841 [M]+. IC50=0.007

Workup

  1. custompurified by preparative HPLC-MS (MeOH/H2O+0.1% TFA)
  2. dissolutionThe product is dissolved in dichloromethane
  3. washwashed with a 2 molar potassiumcarbonate solution
  4. dry with materialdried over sodiumsulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ace4c7256f254dd18d279fc146b3f228
Source dataset
uspto-grants-2015_08
Patent number
US09096548B2

Reaction notes

Loading…