Diisopropylethylamine → HCID 59275129, compound

HRID 1877669Notes

Reaction equation

HRID 1877669 reaction equation
[F:1][C:2]1[C:10]([C:11]2[CH:12]=[CH:13][C:14]3[O:18][C:17]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)=[C:16]([C:26](=[O:29])[NH:27][CH3:28])[C:15]=3[CH:30]=2)=[C:9]([CH3:31])[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].[N:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[C:38]1([NH2:41])[CH2:40][CH2:39]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[F:1][C:2]1[C:3]([C:4](=[O:5])[NH:41][C:38]2([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][N:32]=3)[CH2:40][CH2:39]2)=[CH:7][CH:8]=[C:9]([CH3:31])[C:10]=1[C:11]1[CH:12]=[CH:13][C:14]2[O:18][C:17]([C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)=[C:16]([C:26]([NH:27][CH3:28])=[O:29])[C:15]=2[CH:30]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 111054091-(Pyridin-2-yl)cyclopropanamineHCID 59275131HCID 59275131, compound

Product 1

HCID 59275129HCID 59275129, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the solution of 2-fluoro-3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid (0.1 g, 0.273 mmol, 1.0 eq) in DMF (5.0 ml), 1-(pyridin-2-yl)cyclopropanamine (0.038 g, 0.285 mmol, 1.2 eq), TBTU (0.130 g, 0.403 mmol, 1.7 eq) and DIPEA (0.154 g, 1.187 mmol, 5.0 eq) were added. Mixture was stirred at ambient temperature for 12 h under nitrogen atmosphere. DMF was concentrated and to this residue water was added and extracted with ethyl acetate. The combined organic layer was dried over sodium sulphate and ethyl acetate was evaporated. The crude was purified by preparative TLC eluted with hexane/EtOAc (5:5). The product was further purified by recrystallization with DCM and hexane. Yield: 0.045 g (39%). 1H NMR (400 MHz, DMSO-d6): δ 1.23-1.25 (m, 2H), 1.51-1.54 (m, 2H), 2.18 (s, 3H), 2.81-2.82 (d, 3H, J=4.0 Hz), 7.13-7.15 (t, 1H, J=3.78 Hz), 7.27-7.29 (d, 1H, J=8.00 Hz), 7.33-7.35 (d, 1H, J=4.26 Hz), 7.39-7.44 (m, 3H, J=5.26 Hz), 7.56-7.60 (t, 2H, J=7.56 Hz), 7.68-7.72 (m, 1H), 7.80-7.82 (d, 1H, J=8.44 Hz), 7.96-8.00 (m, 2H), 8.43-8.49 (m, 2H), 9.12 (s, 1H). LCMS: (ES+) m/z=538.0 (M+H). Method: Column: Chromolith SpeedRod C18 (4.6×30) mm, 5 micron Mphase A: 10% MeOH-90% H2O-0.1% TFA Mphase B: 90% MeOH-10% H2O-0.1% TFA Flow: 5 ml/min

Workup

  1. concentrationDMF was concentrated and to this residue water
  2. additionwas added
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organic layer was dried over sodium sulphate and ethyl acetate
  5. customwas evaporated
  6. customThe crude was purified by preparative TLC
  7. washeluted with hexane/EtOAc (5:5)
  8. customThe product was further purified by recrystallization with DCM and hexane

Sources & evidence

ORD record
ord-69c5376ebdcb4c98bcc28f3558df9fb3
Source dataset
uspto-grants-2012_11
Patent number
US08309558B2

Reaction notes

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