Dichloromethane → HCID 90463304, compound

HRID 2278709Notes

Reaction equation

HRID 2278709 reaction equation
I[C:2]1[C:6]([CH2:7][N:8]([CH3:19])[CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:5][N:4]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[N:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:34][N:35]1[C:43]2[C:38](=[CH:39][CH:40]=[C:41](B(O)O)[CH:42]=2)[CH:37]=[N:36]1.C(Cl)Cl>COCCOC.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].CC#N.O>[CH3:19][N:8]([CH2:7][C:6]1[C:2]([C:41]2[CH:42]=[C:43]3[C:38]([CH:37]=[N:36][N:35]3[CH3:34])=[CH:39][CH:40]=2)=[N:3][N:4]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[CH:5]=1)[CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 441182151-Methyl-1H-indazole-6-boronic acidHCID 90433946tert-butyl(2-(((3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)(methyl)amino)ethyl)carbamate

Product 1

HCID 90463304HCID 90463304, compoundYield 25%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of tert-butyl N-[2-([[3-iodo-1-(oxan-2-yl)-1H-pyrazol-4-yl]methyl](methyl)amino)ethyl]carbamate (200 mg, 0.43 mmol, 1.00 equiv), K3PO4 (273 mg, 1.29 mmol, 3.00 equiv), (1-methyl-1H-indazol-6-yl)boronic acid (113 mg, 0.64 mmol, 1.50 equiv) and Pd(dppf)Cl2.CH2Cl2 (70 mg, 0.10 mmol, 0.20 equiv) in ethylene glycol dimethyl ether (20 mL) was stirred under nitrogen at 95° C. overnight. The resulting mixture was cooled to room temperature then concentrated under vacuum. The crude product was purified by Pre-HPLC with the following conditions (1#-Pre-HPLC-005 (Waters)): Column, XBridge Shield RP18 OBD Column, 5 m, 19×150 mm; mobile phase, water with 10 mmol NH4HCO3 and CH3CN (18% CH3CN up to 58% in 10 min, up to 95% in 1 min, down to 18% in 2 min); Detector, UV 254/220 nm to yield 50 mg (25%) of tert-butyl 2-(methyl((3-(1-methyl-1H-indazol-6-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)amino)ethylcarbamate as a colorless oil. LCMS (method A, ESI): RT=1.16 min, m/z=469.0 [M+H]+.

Workup

  1. concentrationthen concentrated under vacuum
  2. customThe crude product was purified by Pre-HPLC with the following conditions (1#-Pre-HPLC-005 (Waters))
  3. waitdown to 18% in 2 min)

Sources & evidence

ORD record
ord-e1e5ef62261947c89e3143553499024a
Source dataset
uspto-grants-2015_09
Patent number
US09133189B2

Reaction notes

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