Triethylamine → HCID 44177300, compound

HRID 1091880Notes

Reaction equation

HRID 1091880 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:26][CH2:25][C:14]2[NH:15][C:16]3[CH:17]=[CH:18][C:19]([C:22](O)=[O:23])=[CH:20][C:21]=3[C:13]=2[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.Cl.[NH2:53][CH:54]1[CH2:59][CH2:58][N:57]([CH2:60][C:61]2[CH:66]=[CH:65][C:64]([C:67]#[N:68])=[CH:63][CH:62]=2)[CH2:56][CH2:55]1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>CN(C=O)C.C(OCC)C.CO.C(Cl)Cl.C(Cl)Cl>[C:67]([C:64]1[CH:65]=[CH:66][C:61]([CH2:60][N:57]2[CH2:58][CH2:59][CH:54]([NH:53][C:22]([C:19]3[CH:18]=[CH:17][C:16]4[NH:15][C:14]5[CH2:25][CH2:26][N:11]([C:9]([O:8][CH2:1][C:2]6[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=6)=[O:10])[CH2:12][C:13]=5[C:21]=4[CH:20]=3)=[O:23])[CH2:55][CH2:56]2)=[CH:62][CH:63]=1)#[N:68]

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 44120478HCID 44120478, compoundHCID 57750052HCID 57750052, compound

Product 1

HCID 44177300HCID 44177300, compound

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of 2-(benzyloxycarbonyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylic acid (3, 0.5 g, 1.4 mmol) in DMF (10 mL), HATU (0.65 g, 1.7 mmol), 4-amino-1-(4-cyanobenzyl)piperidine dihydrochloride (0.41 g, 1.4 mmol) and triethylamine (1.05 mL, 0.76 g, 7.5 mmol) were added. The resulting reaction mixture was allowed to stir at room temperature overnight, poured into saturated sodium bicarbonate solution (75 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were washed with water (2×30 mL), brine (1×30 mL), dried (MgSO4), filtered and concentrated to give a tan solid. Column chromatography (neat DCM→5% MeOH/DCM) provided benzyl 8-(1-(4-cyanobenzyl)piperidin-4-ylcarbamoyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (4a in Scheme 1(b)) as a white solid upon trituration with ethyl ether (0.55 g, 70%). 1H NMR (DMSO-d6, 300 MHZ) 11.14 (br s, 1H), 8.04 (d, J=8.0 Hz, 1H), 8.00 (s, 1H), 7.79 (d, J=8.0 Hz, 2H), 7.59 (d, J=8.5 Hz, 1H), 7.51 (d, J=7.7 Hz, 2H), 7.39-7.27 (m, 6H), 5.14 (s, 2H), 4.67 (br s, 2H), 3.80 (br s, 3H), 3.57 (s, 2H), 2.82 (br s, 4H), 2.08 (t, J=11.0 Hz, 2H), 1.80 (d, J=11.3 Hz, 2H), 1.61 (q, J=10.7 Hz, 2H) ppm; MS (ES) 548 (M+H).

Workup

  1. customThe resulting reaction mixture
  2. extractionextracted with EtOAc (3×50 mL)
  3. washThe combined organic layers were washed with water (2×30 mL), brine (1×30 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a tan solid

Sources & evidence

ORD record
ord-513af95e7be7456a98eb457ace261c1d
Source dataset
uspto-grants-2012_03
Patent number
US08129390B2

Reaction notes

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