Triethylamine → HCID 44177821, compound

HRID 340398Notes

Reaction equation

HRID 340398 reaction equation
[C:1]([C:3]1[CH:41]=[CH:40][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][CH:11]([NH:14][C:15]([C:17]3[CH:25]=[CH:24][C:23]4[NH:22][C:21]5[CH2:26][CH2:27][N:28](C(OCC6C=CC=CC=6)=O)[CH2:29][C:20]=5[C:19]=4[CH:18]=3)=[O:16])[CH2:10][CH2:9]2)=[CH:5][CH:4]=1)#[N:2].Br.CC(O)=O.C(N(CC)CC)C.[F:54][C:55]([F:67])([F:66])[C:56]1[CH:61]=[CH:60][C:59]([S:62](Cl)(=[O:64])=[O:63])=[CH:58][CH:57]=1.C(=O)(O)[O-].[Na+]>ClCCl>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH2:13][CH2:12][CH:11]([NH:14][C:15]([C:17]3[CH:25]=[CH:24][C:23]4[NH:22][C:21]5[CH2:26][CH2:27][N:28]([S:62]([C:59]6[CH:58]=[CH:57][C:56]([C:55]([F:54])([F:66])[F:67])=[CH:61][CH:60]=6)(=[O:64])=[O:63])[CH2:29][C:20]=5[C:19]=4[CH:18]=3)=[O:16])[CH2:10][CH2:9]2)=[CH:40][CH:41]=1)#[N:2]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 27773994-(Trifluoromethyl)benzenesulfonyl chlorideHCID 21893785Acetic Acid Mixture with Hydrobromic AcidHCID 44177300HCID 44177300, compound

Product 1

HCID 44177821HCID 44177821, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of benzyl 8-(1-(4-cyanobenzyl)piperidin-4-ylcarbamoyl)-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (4a, 50 mg, 91 μmol) in DCM (dichloromethane) (1.0 mL) was added dropwise a solution of HBr/AcOH (48% w/v, 1.0 mL). After the resulting brown reaction mixture was stirred for 30 min, the volatiles were evaporated, MeOH (2 mL) was added and the volatiles evaporated again. The resulting brown residue was dissolved in DMF (1.0 mL) and triethylamine (0.5 mL, 0.36 g, 3.6 mmol) and 4-(trifluoromethyl)benzenesulfonyl chloride (45 mg, 0.2 mmol) were added. The resulting reaction mixture was allowed to stir at room temperature overnight, then poured into saturated sodium bicarbonate solution (20 mL) to give a brown precipitate which was filtered and purified by reverse phase HPLC to provide Compound 24 upon trituration with ethyl ether (18 mg, 31%). 1H NMR (DMSO-d6, 300 MHZ) 11.21 (br s, 1H), 11.18 (br s, 1H), 9.75 (br s, 1H), 8.26 (d, J=7.2 Hz, 1H), 8.07 (d, J=8.3 Hz, 2H), 7.98 (d, J=7.7 Hz, 4H), 7.71 (d, J=8.3 Hz, 2H), 7.57 (d, J=8.5 Hz, 1H), 7.28 (d, J=8.5 Hz, 1H), 4.40 (d, J=8.3 Hz, 4H), 3.55-3.06 (m, 7H), 2.92-2.82 (m, 2H), 2.07 (d, J=10.5 Hz, 2H), 1.78 (q, J=11.3 Hz, 2H) ppm; MS (ES) 622 (M+H).

Workup

  1. customthe volatiles were evaporated
  2. additionMeOH (2 mL) was added
  3. customthe volatiles evaporated again
  4. dissolutionThe resulting brown residue was dissolved in DMF (1.0 mL)
  5. customThe resulting reaction mixture
  6. stirringto stir at room temperature overnight
  7. customto give a brown precipitate which
  8. filtrationwas filtered
  9. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-b132a09c4cf04c7486a7ec647a773562
Source dataset
uspto-grants-2014_11
Patent number
US08895578B2

Reaction notes

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