Diisopropylethylamine → HCID 178485569, compound

HRID 2279904Notes

Reaction equation

HRID 2279904 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][CH:30]([PH:32](=[O:34])[OH:33])[CH3:31])=[CH:26][C:25]=3[O:37][CH3:38])[N:14]=2)=[CH:4][CH:3]=1.[CH3:39][C:40]1([CH3:56])[C:44]([CH3:46])([CH3:45])[O:43][B:42]([C:47]2[CH:48]=[N:49][N:50]([CH2:52][CH2:53][CH2:54]O)[CH:51]=2)[O:41]1.CCN(C(C)C)C(C)C.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][CH:30]([PH:32](=[O:33])[O:34][CH2:54][CH2:53][CH2:52][N:50]4[CH:51]=[C:47]([B:42]5[O:43][C:44]([CH3:46])([CH3:45])[C:40]([CH3:39])([CH3:56])[O:41]5)[CH:48]=[N:49]4)[CH3:31])=[CH:26][C:25]=3[O:37][CH3:38])[N:14]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 671871273-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-1-ol2×HCID 178485565HCID 178485565, compound2×

Product 1

HCID 178485569HCID 178485569, compound

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)propan-2-ylphosphinic acid (Compound 68B, 0.240 g, 0.389 mmol) and 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-1-ol (Compound 3E, 97.9 g, 0.388 mmol) in 1,2-dichloroethane (8.53 mL) and DIPEA (0.812 mL, 4.66 mmol) was charged with (benzotriazol-1-yloxy)tripyrrolidino-phosphonium hexafluorophosphate (1.21 g, 2.33 mmol). The reaction mixture was stirred 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→90:10) as eluent to afford the title compound as an off-white foam. MS (ESI): m/z 851.84/853.82 [M+H]+. UPLC: tR=1.57 min (UPLC-SQD: analytical—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

Sources & evidence

ORD record
ord-b7b12b9807bd4852a7c9f65f15a63b12
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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