Potassium Phosphate, Tribasic → 2-Methyl-propane-2-sulfinic acid{1-[6-(6-hydroxymethyl-pyridin-3-yl)-pyridazin-3-yl]-1-methyl-ethyl}-amide

HRID 2038763Notes

Reaction equation

HRID 2038763 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([NH:11][S:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])([CH3:10])[CH3:9])=[CH:4][CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[OH:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][N:29]=1>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].COCCOC.O.CCO>[OH:26][CH2:27][C:28]1[N:29]=[CH:30][C:31]([C:2]2[N:7]=[N:6][C:5]([C:8]([NH:11][S:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])([CH3:10])[CH3:9])=[CH:4][CH:3]=2)=[CH:32][CH:33]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 441182556-(Hydroxymethyl)pyridine-3-boronic acidHCID 889591792-Methyl-propane-2-sulfinic acid[1-(6-chloro-pyridazin-3-yl)-1-methyl-ethyl]-amide

Product 1

HCID 683789692-Methyl-propane-2-sulfinic acid{1-[6-(6-hydroxymethyl-pyridin-3-yl)-pyridazin-3-yl]-1-methyl-ethyl}-amideYield 21.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
140 °C

Procedure

Impure 2-methyl-propane-2-sulfinic acid[1-(6-chloro-pyridazin-3-yl)-1-methyl-ethyl]-amide (15 mg, 0.054 mmol) was combined with Pd(dppf)Cl2.dichloromethane complex (4.7 mg, 0.006 mmol), 1M K3PO4 (0.07 mL, 0.07 mmol) and 2-(hydroxymethyl)pyridine-5-boronic acid (18 mg, 0.12 mmol) in a microwave vial. A 7:3:2 mixture of DME/H2O/EtOH (1 mL) was added. The vial was flushed with argon and sealed. This vial was then heated in the microwave reactor for 15 min at 140° C. The reaction mixture was diluted with 2 mL of water and extracted 4×4 mL with EtOAc. The combined organic layers were dried over MgSO4, filtered and concentrated. Purification via normal phase flash chromatography on silica gel (0→4% MeOH/CH2Cl2) yielded 4 mg of 2-methyl-propane-2-sulfinic acid{1-[6-(6-hydroxymethyl-pyridin-3-yl)-pyridazin-3-yl]-1-methyl-ethyl}-amide as a brown solid.

Workup

  1. additionwas added
  2. customThe vial was flushed with argon
  3. customsealed
  4. additionThe reaction mixture was diluted with 2 mL of water
  5. extractionextracted 4×4 mL with EtOAc
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification via normal phase flash chromatography on silica gel (0→4% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-a989d63ffde34ae1b1bc49a86a35fa15
Source dataset
uspto-grants-2013_11
Patent number
US08575360B2

Reaction notes

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