Acetic Acid → HCID 178510007, compound

HRID 1875263Notes

Reaction equation

HRID 1875263 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][N:5](COCC[Si](C)(C)C)[C:6]=1[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][C:19]2[CH:24]=[C:23]([CH:25]=O)[CH:22]=[C:21]([C:27]#[N:28])[CH:20]=2)[C:12]=1[F:29])=[O:8].[NH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C(O)(C(F)(F)F)=O>ClCCCl>[Cl:1][C:2]1[N:3]=[CH:4][NH:5][C:6]=1[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][C:19]2[CH:24]=[C:23]([CH2:25][N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[CH:22]=[C:21]([C:27]#[N:28])[CH:20]=2)[C:12]=1[F:29])=[O:8]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 86644952HCID 86644952, compound

Product 1

HCID 178510007HCID 178510007, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

4-chloro-N-({4-chloro-3-[(3-cyano-5-formylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (40 mg, 0.071 mmol) and morpholine (6.18 mg, 0.071 mmol) were mixed in 1,2-dichloroethane (2 mL) and treated with sodium triacetoxyborohydride (21 mg, 0.099 mmol) and acetic acid (4.06 μl, 0.071 mmol). The mixture was stirred at RT for 1 h then TFA (2 ml, 26.0 mmol) was added to the solution and stirred for 30 min. The solvent was removed under vacuum and the crude product was purified by Reverse Phase HPLC (MeCN/water 0.1% formic acid) to give 30 mg (84%) of the title compound as a white solid. 1H NMR (400 MHz, methanol-d4) δ ppm 8.08 (s, 1H), 7.61-7.81 (m, 1H), 7.46 (s, 1H), 7.29-7.41 (m, 2H), 7.24 (s, 1H), 7.08-7.19 (m, 1H), 4.63 (s, 2H), 3.52-3.84 (m, 4H), 2.53 (m., 4H). LC-MS (ES+) m/z 502.9 [M+1].

Workup

  1. stirringstirred for 30 min
  2. customThe solvent was removed under vacuum
  3. customthe crude product was purified by Reverse Phase HPLC (MeCN/water 0.1% formic acid)

Sources & evidence

ORD record
ord-b3b0f5a8335e4dffb37613982f702dda
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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