Diisopropylethylamine → HCID 178448224, compound

HRID 2279922Notes

Reaction equation

HRID 2279922 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.[CH2:39]([Sn:43]([CH2:57][CH2:58][CH2:59][CH3:60])([CH2:53][CH2:54][CH2:55][CH3:56])[C:44]1[N:45]=[N:46][N:47]([CH2:49][CH2:50][CH2:51]O)[CH:48]=1)[CH2:40][CH2:41][CH3:42].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][CH2:30][CH2:31][PH:32](=[O:33])[O:34][CH2:51][CH2:50][CH2:49][N:47]4[CH:48]=[C:44]([Sn:43]([CH2:53][CH2:54][CH2:55][CH3:56])([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:57][CH2:58][CH2:59][CH3:60])[N:45]=[N:46]4)=[CH:26][C:25]=3[O:37][CH3:38])[N:14]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 678145653-[4-(tributylstannanyl)-1H-1,2,3-triazol-1-yl]propan-1-ol2×HCID 178485566HCID 178485566, compound2×

Product 1

HCID 178448224HCID 178448224, compoundYield 57.9%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)propylphosphinic acid (Compound 74B, 0.370 g, 0.599 mmol), 3-[4-(tributylstannanyl)-1H-1,2,3-triazol-1-yl]propan-1-ol (Compound 64B, 0.299 g, 0.719 mmol) and DIPEA (0.313 mL, 1.80 mmol) in 1,2-dichloroethane (10.0 mL) was charged with (benzotriazol-1-yloxy)tripyrrolidino-phosphonium hexafluorophosphate (0.936 g, 1.80 mmol). The resulting mixture was stirred at rt for 16 hours. The reaction mixture was quenched with sat. aq. NaHCO3 (10 mL) and extracted with DCM (20 mL). The organic layer was washed with sat. aq. 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. The fractions containing product were combined and concentrated under reduced pressure to yield an off-white solid (352.1 mg, 57.8%). MS (ESI): m/z 1016.90 [M+H]+. UPLC: tR=1.44 min (UPLC-SQD: analytical_non-polar 2 min).

Workup

  1. customThe reaction mixture was quenched with sat. aq. NaHCO3 (10 mL)
  2. extractionextracted with DCM (20 mL)
  3. washThe organic layer was washed with sat. aq. 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-6d288f2232dd44728b7885a66d51b584
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

Loading…