Dichloromethane → HCID 86677778, compound

HRID 1499856Notes

Reaction equation

HRID 1499856 reaction equation
Br[C:2]1[C:3]([O:23][CH2:24][CH3:25])=[C:4]([CH:10]([N:12]2[C:16]3=[N:17][CH:18]=[N:19][C:20]([NH2:21])=[C:15]3[C:14]([CH3:22])=[N:13]2)[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].CC1(C)C(C)(C)OB([C:34]2[CH:35]=[N:36][N:37]([CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH:38]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].ClCCl>C(#N)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[NH2:21][C:20]1[N:19]=[CH:18][N:17]=[C:16]2[N:12]([CH:10]([C:4]3[C:3]([O:23][CH2:24][CH3:25])=[C:2]([C:34]4[CH:35]=[N:36][N:37]([CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH:38]=4)[C:7]([CH3:8])=[C:6]([Cl:9])[CH:5]=3)[CH3:11])[N:13]=[C:14]([CH3:22])[C:15]=12

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 59216326tert-Butyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)acetateHCID 86677776HCID 86677776, compound

Product 1

HCID 86677778HCID 86677778, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 1-[1-(3-bromo-5-chloro-2-ethoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (70 mg, 0.16 mmol) (first peak from Example 195, step 4), tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]acetate (65 mg, 0.21 mmol), sodium carbonate (30.0 mg, 0.28 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (23 mg, 0.028 mmol) in acetonitrile (3 mL)/water (0.7 mL) was degassed with N2 and then stirred at 95° C. for 2 h. The mixture was diluted with methylene chloride, washed with sat. NaHCO3, water, brine, dried over Na2SO4, filtered and concentrated. The product (65 mg, 78%) was purified by chromatography eluting with CH2Cl2/MeOH (max. MeOH 5%). LCMS calculated for C26H33ClN7O3 (M+H)+: m/z=526.2; Found: 526.3.

Workup

  1. customwas degassed with N2
  2. additionThe mixture was diluted with methylene chloride
  3. washwashed with sat. NaHCO3, water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product (65 mg, 78%) was purified by chromatography
  8. washeluting with CH2Cl2/MeOH (max. MeOH 5%)

Sources & evidence

ORD record
ord-3d4870fbc03843aaa7a24bd34dde25e1
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

Loading…