1-Methylimidazole → HCID 178485577, compound

HRID 2279886Notes

Reaction equation

HRID 2279886 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.[Br:34][C:35]1[N:40]=[C:39]([C:41](=[O:44])[NH:42][CH3:43])[C:38]([NH:45][C:46]2[C:51]([C:52]([F:55])([F:54])[F:53])=[CH:50][N:49]=[C:48]([NH:56][C:57]3[CH:67]=[CH:66][C:60]([CH2:61][CH2:62][PH:63](=[O:65])[OH:64])=[CH:59][C:58]=3[O:68][CH3:69])[N:47]=2)=[CH:37][CH:36]=1.[CH3:70][C:71]1([CH3:87])[C:75]([CH3:77])([CH3:76])[O:74][B:73]([C:78]2[CH:79]=[N:80][N:81]([CH2:83][CH2:84][CH2:85]O)[CH:82]=2)[O:72]1.CN1C=CN=C1>ClCCCl>[Br:34][C:35]1[N:40]=[C:39]([C:41](=[O:44])[NH:42][CH3:43])[C:38]([NH:45][C:46]2[C:51]([C:52]([F:55])([F:53])[F:54])=[CH:50][N:49]=[C:48]([NH:56][C:57]3[CH:67]=[CH:66][C:60]([CH2:61][CH2:62][PH:63](=[O:64])[O:65][CH2:85][CH2:84][CH2:83][N:81]4[CH:82]=[C:78]([B:73]5[O:74][C:75]([CH3:77])([CH3:76])[C:71]([CH3:70])([CH3:87])[O:72]5)[CH:79]=[N:80]4)=[CH:59][C:58]=3[O:68][CH3:69])[N:47]=2)=[CH:37][CH:36]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 2724699PyBOPHCID 671871273-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-1-ol2×HCID 178485575HCID 178485575, compound2×

Product 1

HCID 178485577HCID 178485577, compoundYield 16.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

(Benzotriazol-1-yloxy)tripyrrolidino-phosphonium hexafluorophosphate (2.24 g, 4.30 mmol) was added to stirring suspension of (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)methylphosphinic acid (Compound 61B, 845 mg, 1.43 mmol), 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-1-ol (Compound 3E, 362 mg, 1.43 mmol), and 1-methylimidazole (1.37 ml, 17.2 mmol) in 1,2-dichloroethane (31.2 ml) at 60° C. for 16 hrs. The reaction was quenched with water and extracted with EtOAc (3×), dried over sodium sulfate, filtered, and concentrated in vacuo and purified using a Teledyne ISCO Combiflash® Rf system [0→10% MeOH in 1:1 EtOAc/DCM] to afford 194 mg of the title compound as a racemic mixture (16%). MS (ESI): m/z=824.65 [M+H]+. UPLC: tR=1.17 min (UPLC-TOF: polar—2 min).

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with EtOAc (3×)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified

Sources & evidence

ORD record
ord-d451b2fe8edd4f418384ff144aee4158
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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