Potassium Phosphate, Tribasic → HCID 86714782, compound

HRID 1055135Notes

Reaction equation

HRID 1055135 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:5]2=[N:6][CH:7]=1.Cl[C:31]1[N:36]=[C:35]([NH:37][C@@H:38]([C:46]([CH3:49])([CH3:48])[CH3:47])[CH2:39][CH:40]([OH:45])[C:41]([F:44])([F:43])[F:42])[C:34]([F:50])=[CH:33][N:32]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:43][C:41]([F:42])([F:44])[CH:40]([OH:45])[CH2:39][C@@H:38]([NH:37][C:35]1[C:34]([F:50])=[CH:33][N:32]=[C:31]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([F:1])[CH:3]=3)[N:8]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:21])=[O:22])[CH:9]=2)[N:36]=1)[C:46]([CH3:49])([CH3:47])[CH3:48]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672856905-fluoro-1-((4-methylphenyl)sulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridine2×HCID 86714783HCID 86714783, compound

Product 1

HCID 86714782HCID 86714782, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 5-fluoro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (0.091 g, 0.218 mmol), 7a, (4R)-4-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]-1,1,1-trifluoro-5,5-dimethyl-hexan-2-ol, 180a, (0.060 g, 0.182 mmol) and K3PO4 (0.116 g, 0.546 mmol) in 2-methyl THF (5 mL) and H2O (1.5 mL) was degassed under a stream of nitrogen for 45 minutes. To the reaction mixture was added X-phos (0.010 g, 0.022 mmol) and Pd2(dba)3 (0.004 g, 0.005 mmol). The reaction mixture was stirred at 120° C. in a pressure tube for 2 hours. The aqueous phase was removed. The organic phase was filtered through a pad of celite and concentrated in vacuo. The resulting residue was purified via silica gel chromatography (40% EtOAc/Hexanes) to afford 60 mg of the desired product: 1H NMR (400 MHz, CDCl3) δ 8.41 (s, 1H), 8.37 (dd, J=8.9, 2.8 Hz, 1H), 8.24 (t, J=8.7 Hz, 1H), 8.16 (d, J=2.9 Hz, 1H), 8.00 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.1 Hz, 2H), 4.92 (t, J=7.8 Hz, 2H), 4.44 (t, J =10.3 Hz, 1H), 4.06 (s, 1H), 2.34 (s, 3H), 2.13 (dt, J=13.6, 4.9 Hz, 1H), 1.66 (dd, J=23.0, 9.3 Hz, 1H), 1.07 (d, J=8.4 Hz, 9H). LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, Retention Time=4.02 min (M+H) 584.41.

Workup

  1. customThe aqueous phase was removed
  2. filtrationThe organic phase was filtered through a pad of celite
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified via silica gel chromatography (40% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-7256584cdff949bfb038274bdd49680a
Source dataset
uspto-grants-2016_07
Patent number
US09394302B2

Reaction notes

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