Tetrahydrofuran → HCID 25124640, compound

HRID 1272700Notes

Reaction equation

HRID 1272700 reaction equation
[CH:1]1([CH2:4][NH:5][C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17](C(O)=O)[CH:16]=3)=[CH:11]C=2)=[O:7])[CH2:3][CH2:2]1.C1CN([P+](ON2N=[N:48][C:43]3[CH:44]=[CH:45][CH:46]=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C1(CN)CC1.[CH3:62]CN(C(C)C)C(C)C.C1C[O:74][CH2:73]C1>>[CH:1]1([CH2:4][NH:5][C:6]([C:8]2[CH:11]=[C:12]([C:15]3[CH:16]=[CH:17][C:18]([C:73]([NH:48][CH2:43][CH:44]4[CH2:45][CH2:46]4)=[O:74])=[CH:19][CH:20]=3)[C:13]([CH3:62])=[CH:14][CH:9]=2)=[O:7])[CH2:2][CH2:3]1

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 75646CyclopropanemethanamineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 18457811HCID 18457811, compound

Product 1

HCID 25124640HCID 25124640, compound

Procedure

{4′-[(Cyclopropylmethylamino)carbonyl]methyl-1,1′-biphenyl-3-yl}carboxylic acid (26 mg, 0.084 mmol, PyBOP (44 mg, 0.084 mmol) and cyclopropylmethylamine (7 mg, 0.1 mmol) were mixed in THF (2 ml) and DIPEA (44 μl) added, the reaction was stirred at room temperature for 18 h. The solvent was evaporated under vacuum and reaction was partitioned between DCM (2 ml) and aqueous sodium carbonate solution (1M, 2 ml). The organic fraction was purified on a silica SPE (5 g) eluting with DCM, chloroform, diethyl ether, ethyl acetate, acetonitrile, acetone, ethanol, methanol and DCM/ethanol/ammonia (20:8:1 then 15:8:1). Product fractions combined and evaporated to dryness to give the N3-cyclopropylmethyl-N4′-cyclopropylmethyl-6-methyl-1,1′-biphenyl-3,4′-dicarboxamide. NMR: δH [2H6]-DMSO 8.63, (1H, t), 8.57, (1H, t), 7.94, (2H, d), 7.78, (1H, dd), 7.73, (1H, d), 7.48, (2H, d), 7.40, (1H, d), 3.18–3.10, (4H, m), 2.27, (3H, s), 1.02, (2H, m), 0.42, (4H, m), 0.22, (4H, m). LCMS: retention time 3.32 min, MH+363.

Workup

  1. customThe solvent was evaporated under vacuum and reaction
  2. customwas partitioned between DCM (2 ml) and aqueous sodium carbonate solution (1M, 2 ml)
  3. customThe organic fraction was purified on a silica SPE (5 g)
  4. washeluting with DCM, chloroform, diethyl ether, ethyl acetate, acetonitrile, acetone, ethanol, methanol and DCM/ethanol/ammonia (20:8:1
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-92c05065a99948b4842285c34fce0e1f
Source dataset
uspto-grants-2007_04
Patent number
US07208629B2

Reaction notes

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