Triethylamine → 1-Phenylcyclopentanecarboxylic Acid [4a-(3-Methoxyphenyl)-8a-methyl-2-(3-phenylpropyl)octahydroisoquinolin-6-yl]amide

HRID 1453978Notes

Reaction equation

HRID 1453978 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][N:10]2[CH2:19][CH2:18][C:17]3([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=4)[C:12]([CH3:29])([CH2:13][CH2:14][CH:15]([NH2:28])[CH2:16]3)[CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:30]1([C:36]2([C:41](O)=[O:42])[CH2:40][CH2:39][CH2:38][CH2:37]2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(N(CC)CC)C.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1.C(Cl)Cl.CCOC(C)=O>[CH3:27][O:26][C:22]1[CH:21]=[C:20]([C:17]23[CH2:16][CH:15]([NH:28][C:41]([C:36]4([C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=5)[CH2:40][CH2:39][CH2:38][CH2:37]4)=[O:42])[CH2:14][CH2:13][C:12]2([CH3:29])[CH2:11][N:10]([CH2:9][CH2:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:19][CH2:18]3)[CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 661671-Phenylcyclopentanecarboxylic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 68827565N-(3-Phenylpropyl)-6-amino-4a-(3-methoxyphenyl)-8a-methyloctahydroisoquinoline

Product 1

HCID 730003781-Phenylcyclopentanecarboxylic Acid [4a-(3-Methoxyphenyl)-8a-methyl-2-(3-phenylpropyl)octahydroisoquinolin-6-yl]amide

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To compound 24 (71 mg, 0.180 mmol) dissolved in anhydrous THF (15 mL) was added 1-phenyl-1-cyclopentanecarboxylic acid (51 mg, 0.27 mmol), triethylamine (0.126 mL, 0.904 mmol), and BOP reagent (88 mg, 0.20 mmol), and the reaction mixture was allowed to stir at room temperature for 2 h. Reaction progress was monitored by TLC (30% CMA 80 in CH2Cl2). The reaction mixture was diluted with EtOAc (25 mL) and washed with saturated aqueous NaHCO3 (25 mL) followed by water (25 mL). The aqueous layers were back extracted with EtOAc (2×20 mL). The combined organic layers were washed with 1 N NaOH (30 mL), dried (MgSO4), and concentrated under reduced pressure to afford crude product. The crude product was purified by flash chromatography (25% CMA 80 in CH2Cl2) to afford 94 mg (92%): LCMS (ESI): m/z 565.6 (M+H)+; 1H NMR (CDCl3, 300 MHz) δ 7.17-7.36 [m, 13H], 6.71-6.73 [m, 1H], 4.92, [d, J=6 Hz, 1H], 4.19 [m, 1H], 3.79 [s, 3H], 2.74 [br, 1H], 2.62-2.64 [m, 2H], 2.33-2.45 [m, 5H], 2.10-2.31 [m, 2H], 1.98-2.09 [m, 3H], 1.61-1.84 [m, 10H], 1.46 [d, J=12 Hz, 1H], 1.20-1.33 [m, 2H], 1.15 [s, 3H]; 13C NMR (CDCl3, 300 MHz) δ 176.1, 159.2, 148.9, 144.8, 142.8, 129.0, 128.9, 128.7, 128.6, 127.2, 127.1, 126.0, 121.9, 116.3, 110.7, 62.2, 59.6, 58.2, 55.5, 51.2, 46.2, 44.2, 37.8, 37.4, 37.2, 36.9, 36.6, 35.6, 33.9, 29.2, 28.1, 26.6, 24.4.

Workup

  1. customReaction progress
  2. washwashed with saturated aqueous NaHCO3 (25 mL)
  3. extractionThe aqueous layers were back extracted with EtOAc (2×20 mL)
  4. washThe combined organic layers were washed with 1 N NaOH (30 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customto afford crude product
  8. customThe crude product was purified by flash chromatography (25% CMA 80 in CH2Cl2)
  9. customto afford 94 mg (92%)

Sources & evidence

ORD record
ord-ecc494aeb40d440d8a0f2b7b9ee6e7ea
Source dataset
uspto-grants-2009_01
Patent number
US07476679B2

Reaction notes

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