Triethylamine → HCID 44178171, compound

HRID 340409Notes

Reaction equation

HRID 340409 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:36][CH2:35][C:11]3[NH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([NH:21][CH:22]5[CH2:27][CH2:26][N:25]([C:28]([O:30]C(C)(C)C)=O)[CH2:24][CH2:23]5)=[O:20])=[CH:17][C:18]=4[C:10]=3[CH2:9]2)=[CH:4][CH:3]=1.[F:37][C:38]1[CH:46]=[CH:45][C:41](C(Cl)=O)=[CH:40][CH:39]=1.C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>Cl.O1CCOCC1>[F:37][C:38]1[CH:46]=[CH:45][C:41]([C:28]([N:25]2[CH2:26][CH2:27][CH:22]([NH:21][C:19]([C:16]3[CH:15]=[CH:14][C:13]4[NH:12][C:11]5[CH2:35][CH2:36][N:8]([C:5]6[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=6)[CH2:9][C:10]=5[C:18]=4[CH:17]=3)=[O:20])[CH2:23][CH2:24]2)=[O:30])=[CH:40][CH:39]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 678794-Fluorobenzoyl chlorideHCID 516892Sodium BicarbonateHCID 44178170HCID 44178170, compound2×

Product 1

HCID 44178171HCID 44178171, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 204431481,4-Dioxane hydrochlorideSolvent

Procedure

A solution of tert-butyl 4-(2-(4-fluorophenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamido)piperidine-1-carboxylate (Compound 38, 50 mg, 100 μmol) in 4 N HCl/dioxane (3.0 mL) was allowed to stir at room temperature for 2 h. The reaction mixture was then concentrated, MeOH (5.0 mL) was added and the volatiles were evaporated (2×). The resulting residue was dissolved in DMF (2.0 mL) and 4-fluorobenzoyl chloride (15 μL, 20 mg, 130 μmol) and triethylamine (0.5 mL, 0.36 g, 3.6 mmol) were added. The resulting reaction mixture was allowed to stir at room temperature overnight, poured into saturated sodium bicarbonate solution (20 mL) to give a yellow solid which was triturated with ethyl ether and then purified by reverse phase HPLC to provide N-(1-(4-fluorobenzoyl)piperidin-4-yl)-2-(4-fluorophenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide (Compound 39) (46%). 1H NMR (DMSO-d6, 300 MHZ) 11.13 (s, 1H), 8.09 (d, J=7.7 Hz, 1H), 8.03 (s, 1H), 7.58 (dd, J=8.4, 1.5 Hz, 1H), 7.45 (dd, J=8.5, 5.5 Hz, 2H), 7.28 (t, J=8.8 Hz, 3H), 7.10 (m, 4H), 4.43 (s, 3H), 4.18-4.03 (m, 2H), 3.70-3.54 (m, 3H), 3.16 (br s, 1H), 2.92 (br s, 2H), 1.87 (br s, 2H), 1.54 (br s, 2H) ppm; MS (ES) 515 (M+H).

Workup

  1. concentrationThe reaction mixture was then concentrated
  2. additionMeOH (5.0 mL) was added
  3. customthe volatiles were evaporated (2×)
  4. dissolutionThe resulting residue was dissolved in DMF (2.0 mL)
  5. customThe resulting reaction mixture
  6. stirringto stir at room temperature overnight
  7. customto give a yellow solid which
  8. customwas triturated with ethyl ether
  9. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-dd634c38a2e245f8a4705afe2afef49d
Source dataset
uspto-grants-2014_11
Patent number
US08895578B2

Reaction notes

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