Diisopropylethylamine → (1R,2R)-N-(1-cyanocyclopropyl)-2-(6-(2-(dimethylamino)ethoxy)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamide

HRID 1677040Notes

Reaction equation

HRID 1677040 reaction equation
[C:1]1(=[O:11])[C@H:9]2[C@@H:4]([CH2:5][CH2:6][CH2:7][CH2:8]2)[C:3](=[O:10])O1.[CH3:12][N:13]([CH3:30])[CH2:14][CH2:15][O:16][C:17]1[C:25]2[NH:24][C:23]3[CH2:26][CH2:27][NH:28][CH2:29][C:22]=3[C:21]=2[CH:20]=[CH:19][CH:18]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=[N:55][C:50]2[CH:51]=[CH:52]C=[N:54][C:49]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.NC1(C#N)CC1>CN(C=O)C>[C:49]([C:50]1([NH:55][C:1]([C@@H:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C@H:4]2[C:3]([N:28]2[CH2:27][CH2:26][C:23]3[NH:24][C:25]4[C:17]([O:16][CH2:15][CH2:14][N:13]([CH3:30])[CH3:12])=[CH:18][CH:19]=[CH:20][C:21]=4[C:22]=3[CH2:29]2)=[O:10])=[O:11])[CH2:52][CH2:51]1)#[N:54]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942665trans-Cyclohexane-1,2-dicarboxylic anhydrideHCID 145863631-Amino-1-cyclopropanecarbonitrile hydrochlorideHCID 57541284N,N-dimethyl-2-(2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-6-yloxy)ethanamine

Product 1

HCID 25112828(1R,2R)-N-(1-cyanocyclopropyl)-2-(6-(2-(dimethylamino)ethoxy)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamideYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(3aR,7aR)-hexahydroisobenzofuran-1,3-dione (125 mg, 0.81 mmol) was added to N,N-dimethyl-2-(2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-6-yloxy)ethanamine (210 mg, 0.81 mmol) in DMF (10 ml) at room temperature under air. The resulting solution was stirred at room temperature for 2 hours. N,N-Diisopropylethylamine (0.535 ml, 3.24 mmol), HATU (462 mg, 1.21 mmol) and 1-amino-1-cyclopropanecarbonitrile HCL (144 mg, 1.21 mmol) were then added to the mixture. The resulting solution was stirred at room temperature for 20 hours. The crude product was purified by preparative HPLC (0.1% NH3, CH3CN/H2O gradient) as eluents to afford as a brown gum (89 mg, 23%).

Workup

  1. stirringThe resulting solution was stirred at room temperature for 20 hours
  2. customThe crude product was purified by preparative HPLC (0.1% NH3, CH3CN/H2O gradient) as eluents

Sources & evidence

ORD record
ord-ab4c8d1c547e4a7cb2168ab6c119c52e
Source dataset
uspto-grants-2011_08
Patent number
US08008279B2

Reaction notes

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