1-Methylimidazole → HCID 178485568, compound

HRID 2279917Notes

Reaction equation

HRID 2279917 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[C:5]([NH:12][C:13]2[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:36]=[CH:35][C:27]([CH2:28][CH2:29][CH2:30][CH2:31][PH:32](=[O:34])[OH:33])=[CH:26][C:25]=3[O:37][CH3:38])[N:14]=2)=[CH:4][CH:3]=1.[CH3:39][C:40]([CH3:58])([CH2:43][N:44]1[CH:48]=[C:47]([B:49]2[O:53][C:52]([CH3:55])([CH3:54])[C:51]([CH3:57])([CH3:56])[O:50]2)[CH:46]=[N:45]1)[CH2:41]O.CN1C=CN=C1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>ClCCCl>[Br:1][C:2]1[N:7]=[C:6]([C:8](=[O:11])[NH:9][CH3:10])[C:5]([NH:12][C:13]2[C:18]([C:19]([F:22])([F:20])[F:21])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:36]=[CH:35][C:27]([CH2:28][CH2:29][CH2:30][CH2:31][PH:32](=[O:33])[O:34][CH2:39][C:40]([CH3:58])([CH3:41])[CH2:43][N:44]4[CH:48]=[C:47]([B:49]5[O:53][C:52]([CH3:55])([CH3:54])[C:51]([CH3:57])([CH3:56])[O:50]5)[CH:46]=[N:45]4)=[CH:26][C:25]=3[O:37][CH3:38])[N:14]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 2724699PyBOPHCID 678124422,2-Dimethyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propan-1-ol2×HCID 178485566HCID 178485566, compound2×

Product 1

HCID 178485568HCID 178485568, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)propylphosphinic acid (Compound 74B, 0.500 g, 0.810 mmol) and 2,2-dimethyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-1-ol (Compound 47B, 227 mg, 0.809 mmol) in 1,2-dichloroethane (24.4 mL) and 1-methylimidazole (0.967 mL, 12.1 mmol) was charged with (benzotriazol-1-yloxy)tripyrrolidino-phosphonium hexafluorophosphate (2530 mg, 4.85 mmol). After stirring at 60° C. for 16 hours, the reaction mixture was quenched with water (10 mL) and extracted with DCM (20 mL). The organic layer was washed with NaHCO3 (10 mL), washed with brine (15 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to a brown oil. The crude material was purified using a Teledyne ISCO Combiflash® Rf system using 1:1 DCM-EtOAc/MeOH (100:0→95:5) as eluent. The fractions containing product were combined and concentrated under reduced pressure to yield an off-white foam (318.1 mg, 45%). MS (ESI): m/z 879.93/881.94 [M+H]+. UPLC: tR=1.67 min (UPLC-TOF: polar—2 min).

Workup

  1. customthe reaction mixture was quenched with water (10 mL)
  2. extractionextracted with DCM (20 mL)
  3. washThe organic layer was washed with NaHCO3 (10 mL)
  4. washwashed with brine (15 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure to a brown oil
  8. customThe crude material was purified
  9. additionThe fractions containing product
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6b233bbab1154284b426ae441e3160bb
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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