Diisopropylethylamine → HCID 22266077, compound

HRID 489603Notes

Reaction equation

HRID 489603 reaction equation
F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH3:23][S:24][C:25]1[S:29][C:28]([C:30]([OH:32])=O)=[C:27]2[CH2:33][CH2:34][CH2:35][C:36](=[O:37])[C:26]=12.C(N(C(C)C)CC)(C)C.[C:47]([O:51][C:52]([N:54]([CH2:62][C:63]1[CH:64]=[C:65]([CH:69]2[CH2:74][CH2:73][NH:72][CH2:71][CH2:70]2)[CH:66]=[CH:67][CH:68]=1)[C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])=[O:53])([CH3:50])([CH3:49])[CH3:48]>CN(C)C=O>[C:58]([O:57][C:55]([N:54]([CH2:62][C:63]1[CH:64]=[C:65]([CH:69]2[CH2:70][CH2:71][N:72]([C:30]([C:28]3[S:29][C:25]([S:24][CH3:23])=[C:26]4[C:36](=[O:37])[CH2:35][CH2:34][CH2:33][C:27]=34)=[O:32])[CH2:73][CH2:74]2)[CH:66]=[CH:67][CH:68]=1)[C:52]([O:51][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:53])=[O:56])([CH3:59])([CH3:60])[CH3:61]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 6583903-methylsulfanyl-4-oxo-6,7-dihydro-5H-2-benzothiophene-1-carboxylic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 222661574-[3-(N,N-di-tert-butoxycarbonylaminomethyl)phenyl]piperidine

Product 1

HCID 22266077HCID 22266077, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) (120 mg, 0.38 mmol) was added to a room temperature solution of 3-methylsulfanyl-4-oxo-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid (88 mg, 0.36 mmol) and diisopropylethylamine (140 mg, 1.08 mmol) in dimethylformamide (2 mL), under nitrogen. The reaction mixture was stirred for 10 minutes at room temperature before adding a solution of 4-[3-(N,N-di-tert-butoxycarbonylaminomethyl)phenyl]piperidine (140 mg, 0.36 mmol) and diisopropylethylamine (140 mg, 1.08 mmol) in dimethylformamide (2 mL). The reaction mixture was stirred at room temperature for 16 hours, concentrated to dryness in vacuo, and subjected to dry flash column chromatography on silica with 50:50, dichloromethane:ethyl acetate. 1-{1-[4-(3-(N,N-di-tert -butoxycarbonylaminomethyl)phenyl)-piperidin-1-yl]-methanoyl}-3-methylsulfanyl-6,7-dihydro-5H-benzo[c]thiophen-4-one was isolated as a colorless oil (177 mg). The intermediate was dissolved in dichloromethane (20 mL), cooled at 0° C., and treated with trifluoroacetic acid (2 mL). The reaction mixture was stirred at room temperature under nitrogen for 2 hours, and concentrated to dryness in vacuo. The residue was dissolved in 20% acetonitrile/water [containing 0.1% trifluoroacetic acid] (9 mL) and purified by preparative reverse-phase HPLC (C-18, 10 micron reverse-phase column), eluting with 10% to 100% acetonitrile/water (containing 0.1% trifluoroacetic acid). The product fractions were combined and the acetonitrile removed in vacuo. The aqueous residue was frozen and lyophilized to give the title compound as an amorphous white solid (122 mg, 64%). 1H NMR [(CD3)2SO]: δ 8.16 (br s, 3H, NH3+); 7.41-7.24 (m, 4H); 4.21 (br d, 2H); 4.03 (q, 2H); 3.18-3.02 (m, 2H); 2.91-2.72 (m, 3H); 2.59 (s, 3H); 2.53-2.41 (m, 2H); 1.98-1.90 (m, 2H); 1.90-1.79 (m, 2H); 1.68-1.50 (m, 2H). MS(Ion spray): 415 (M++1).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 16 hours
  2. concentrationconcentrated to dryness in vacuo
  3. dry with materialto dry flash column chromatography on silica with 50:50, dichloromethane

Sources & evidence

ORD record
ord-0431cdf1071344ccaba9e4f3123cf102
Source dataset
uspto-grants-2005_12
Patent number
US06977263B2

Reaction notes

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