Triethylamine → HCID 44433598, compound

HRID 915113Notes

Reaction equation

HRID 915113 reaction equation
Cl.[CH3:2][O:3][C:4]([C:6]1[S:10][C:9]2[CH:11]=[C:12]([F:15])[CH:13]=[CH:14][C:8]=2[C:7]=1[CH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[O:5].C(N(CC)CC)C.[CH3:29][S:30]([N:33]1[CH2:38][CH2:37][C:36]2[N:39]([CH2:52][CH2:53][CH:54]=O)[N:40]=[C:41]([C:42]3[CH:47]=[CH:46][C:45]([C:48]([F:51])([F:50])[F:49])=[CH:44][CH:43]=3)[C:35]=2[CH2:34]1)(=[O:32])=[O:31].C([O-])(O)=O.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH3:2][O:3][C:4]([C:6]1[S:10][C:9]2[CH:11]=[C:12]([F:15])[CH:13]=[CH:14][C:8]=2[C:7]=1[CH:16]1[CH2:21][CH2:20][N:19]([CH2:54][CH2:53][CH2:52][N:39]2[C:36]3[CH2:37][CH2:38][N:33]([S:30]([CH3:29])(=[O:32])=[O:31])[CH2:34][C:35]=3[C:41]([C:42]3[CH:47]=[CH:46][C:45]([C:48]([F:50])([F:49])[F:51])=[CH:44][CH:43]=3)=[N:40]2)[CH2:18][CH2:17]1)=[O:5]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 222938973-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propionaldehydeHCID 69181929HCID 69181929, compound

Product 1

HCID 44433598HCID 44433598, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 410 mg (1.25 mmol) of 6-fluoro-3-piperidin-4-yl-benzo[b]thiophene-2-carboxylic acid methyl ester hydrochloride salt in 10 mL of dichloromethane and 0.18 mL (1.25 mmol) of triethylamine was added 500 mg of 3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propionaldehyde (1.25 mmol) and 2 g of NaHCO3. The mixture was stirred for 4 h before the portion wise addition of 792 mg (3.73 mmol) sodium triacetoxyborohydride. The reaction was stirred at room temperature for 3 h before quenching with 20 mL of water. The aqueous phase was extracted with CH2Cl2 (3×50 mL). The combined organic layers were then washed with brine, dried over Na2SO4, and concentrated. The crude product was purified by column chromatography (silica, 0-5% MeOH/CH2Cl2) to afford 650 mg (77%) of a white solid. MS (electrospray): exact mass calculated for C32H34F4N4O4S2: 678.20; m/z found, 679.2 [M+H]+. 1H NMR (CDCl3, 400 MHz): 7.74 and 7.66 (A and B of AB quartet, J=8.22 Hz, 4H), 7.50 (dd, J=8.41, 2.54 Hz 1H), 7.14 (t, J=8.22 Hz, 1H), 4.56 (s, 2H), 4.17 (m, 3H), 3.91 (s, 3H), 3.70 (t, J=5.67 Hz, 2H), 3.03 (br m, 2H), 3.00 (t, J=5.67 Hz, 2H), 2.90 (s, 3H), 2.40 (br m, 4H), 2.13 (br m, 4H), 1.76 (br d, J=11.15 Hz, 4H).

Workup

  1. custombefore quenching with 20 mL of water
  2. extractionThe aqueous phase was extracted with CH2Cl2 (3×50 mL)
  3. washThe combined organic layers were then washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (silica, 0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-d1d998e40bec49009239750e9b133bc0
Source dataset
uspto-grants-2007_09
Patent number
US07265102B2

Reaction notes

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