Diisopropylethylamine → HCID 178432756, compound

HRID 1875117Notes

Reaction equation

HRID 1875117 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][CH2:26][C:27]1[C:28]([F:44])=[C:29]([O:34][C:35]2[CH:36]=[C:37]([CH:40]=[C:41]([Cl:43])[CH:42]=2)[C:38]#[N:39])[C:30]([Cl:33])=[CH:31][CH:32]=1.[CH3:45][C:46]1[N:47]=[C:48]([CH:62]([CH3:64])[CH3:63])[N:49](COCC[Si](C)(C)C)[C:50]=1[C:51](O)=[O:52].C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([CH2:26][NH:25][C:51]([C:50]2[NH:49][C:48]([CH:62]([CH3:63])[CH3:64])=[N:47][C:46]=2[CH3:45])=[O:52])=[C:28]([F:44])[C:29]=1[O:34][C:35]1[CH:36]=[C:37]([C:38]#[N:39])[CH:40]=[C:41]([Cl:43])[CH:42]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 68486406HCID 68486406, compound

Product 1

HCID 178432756HCID 178432756, compoundYield 60.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (103 mg, 0.27 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (56.2 mg, 0.18 mmol), 4-methyl-2-(1-methylethyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (54 mg, 0.18 mmol) and diisopropylethylamine (47 uL, 0.27 mmol) in DMF (1 mL). The reaction mixture was stirred at RT overnight and the solvent was removed under vacuum. The residue was dried in vacuo and the residue was treated with TFA (0.5 mL) in DCM (1.0 mL) at RT and stirred overnight. Neutralized with saturated NaHCO3 and extracted with 10% MeOH in DCM. The organic layer was dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (0-5% 2M NH3 solution of MeOH in DCM) and HPLC to afford the title compound (50 mg, 60%) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.68 (1H, br. s.) 7.56 (1H, br. s.) 7.31-7.40 (2H, m) 7.23 (1H, s) 7.14 (1H, d, J=1.3 Hz) 7.02 (1H, s) 4.62 (2H, d, J=6.4 Hz) 2.96 (1H, dt, J=13.7, 6.8 Hz) 2.56 (3H, s) 1.30 (6H, d, J=7.0 Hz). LCMS: m/z 461 (M+1).

Workup

  1. customthe solvent was removed under vacuum
  2. customThe residue was dried in vacuo
  3. additionthe residue was treated with TFA (0.5 mL) in DCM (1.0 mL) at RT
  4. stirringstirred overnight
  5. extractionNeutralized with saturated NaHCO3 and extracted with 10% MeOH in DCM
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (0-5% 2M NH3 solution of MeOH in DCM) and HPLC

Sources & evidence

ORD record
ord-dc58c092ad01411f9a5ce45d388c5fea
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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