1-Hydroxybenzotriazole → HCID 59275245, compound

HRID 1877666Notes

Reaction equation

HRID 1877666 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([C:19]2[CH:20]=[CH:21][C:22]3[O:26][C:25]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)=[C:24]([C:34](=[O:37])[NH:35][CH3:36])[C:23]=3[CH:38]=2)[C:17]=1[CH3:18])[C:12](O)=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[C:45]1([NH2:48])[CH2:47][CH2:46]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH2:1]([O:8][C:9]1[C:17]([CH3:18])=[C:16]([C:19]2[CH:20]=[CH:21][C:22]3[O:26][C:25]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)=[C:24]([C:34]([NH:35][CH3:36])=[O:37])[C:23]=3[CH:38]=2)[CH:15]=[C:11]([C:12](=[O:13])[NH:48][C:45]2([C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][N:39]=3)[CH2:47][CH2:46]2)[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 111054091-(Pyridin-2-yl)cyclopropanamineHCID 59275775HCID 59275775, compound

Product 1

HCID 59275245HCID 59275245, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-(benzyloxy)-5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid (0.2 g, 0.40 mmol, 1 eq), 1-(pyridin-2-yl)cyclopropanamine (0.064 g, 0.47 mmol, 1.2 eq) (60% purity), HOBT (0.68 g, 0.012 mmol, 1.7 eq), EDC.HCl (0.064 g, 0.72 mmol, 1.8 eq) in DCM at ambient temperature under nitrogen was added Diisopropylethylamine (0.26 g, 2.0 mmol, 5.0 eq). The clear mixture was stirred at ambient temperature for 12 h. The mixture was concentrated, diluted with water and extracted with EtOAc. The organic layer was further washed with water, dried over sodium sulphate and concentrated. The product obtained was further purified by column chromatography (neutral alumina) using 0.5% Methanol/DCM and preparative HPLC. Yield: 0.17 g (70%). 1H NMR (400 MHz, DMSO-d6): δ 1.26-1.27 (m, 2H), 1.54-1.56 (m, 2H), 2.18 (s, 3H), 2.81-2.82 (s, 3H), 5.26 (s, 2H) 7.13-7.15 (q, 1H, J=4.4 Hz), 7.30-7.43 (m, 6H), 7.58 (d, 4H), 7.65-7.69 (t, 2H, J=3.9 Hz), 7.74-7.79 (d, 1H, J=8.0 Hz), 7.97-8.01 (m, 2H), 8.43-8.48 (dd, 2H, J=4.89 Hz), 9.186 (s, 1H). LCMS: (ES+) m/z=626 (M+H) Ascentis Express C18 (5.0×2.1-2.7 μm) Mphase A: 2% MeCN-98% H2O-10 mM NH4COOH Mphase B: 98% MeCN-2% H2O-10 mM NH4COOH

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with water
  3. extractionextracted with EtOAc
  4. washThe organic layer was further washed with water
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. customThe product obtained
  8. customwas further purified by column chromatography (neutral alumina)

Sources & evidence

ORD record
ord-412793f239254647a029dc816a574473
Source dataset
uspto-grants-2012_11
Patent number
US08309558B2

Reaction notes

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