Hydrochloric Acid → HCID 68165434, compound

HRID 921320Notes

Reaction equation

HRID 921320 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[S:15]([CH:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])[C:5]([Cl:21])=[CH:4][N:3]=1.[CH2:22]([N:29]1[CH2:34][CH2:33][P:32]([C:36]2[CH:42]=[CH:41][C:39]([NH2:40])=[C:38]([O:43][CH3:44])[CH:37]=2)(=[O:35])[CH2:31][CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.Cl.[OH-].[Na+]>COCCO>[CH2:22]([N:29]1[CH2:30][CH2:31][P:32]([C:36]2[CH:42]=[CH:41][C:39]([NH:40][C:2]3[N:7]=[C:6]([NH:8][C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=4[S:15]([CH:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])[C:5]([Cl:21])=[CH:4][N:3]=3)=[C:38]([O:43][CH3:44])[CH:37]=2)(=[O:35])[CH2:33][CH2:34]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 597643782,5-dichloro-N-(2-((1-methylethyl)sulfonyl)phenyl)-4-pyrimidinamineHCID 67052723HCID 67052723, compound

Product 1

HCID 68165434HCID 68165434, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2,5-dichloro-N-[2-(propan-2-ylsulfonyl)phenyl]pyrimidin-4-amine (47.3 mg, 0.137 mmol) in 1.5 mL of 2-methoxyethanol was added 4-(1-benzyl-4-oxido-1,4-azaphosphinan-4-yl)-2-methoxyaniline (43.0 mg, 0.13 mmol) and ethanolic HCl (0.10 mL, 2.5 M). The mixture was heated in a sealed vial at 90° C. for 16 h. The reaction was then heated at 100° C. for an additional 2 h. The mixture was basified with 1N NaOH solution, and extracted with ethyl acetate. The organic layers were combined, washed with saturated sodium chloride solution, dried with sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (0-12% 7N ammonia in methanol:dichloromethane) to afford the desired product (43.0 mg, 52% yield).

Workup

  1. temperatureThe reaction was then heated at 100° C. for an additional 2 h
  2. extractionextracted with ethyl acetate
  3. washwashed with saturated sodium chloride solution
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by silica gel chromatography (0-12% 7N ammonia in methanol:dichloromethane)

Sources & evidence

ORD record
ord-2d6fc7c134384de4aed0e7f023696fed
Source dataset
uspto-grants-2016_03
Patent number
US09273077B2

Reaction notes

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