Toluene → Methyl N-[(2S)-1-[(4-{3-[2,6-difluoro-3-(propane-1-sulfonamido)phenyl]-1-(propan-2-yl)-1H-pyrazol-4-yl}pyrimidin-2-yl)amino]propan-2-yl]carbamate

HRID 629511Notes

Reaction equation

HRID 629511 reaction equation
[F:1][C:2]1[C:7](B2OC(C)(C)C(C)(C)O2)=[C:6]([F:17])[CH:5]=[CH:4][C:3]=1[NH:18][S:19]([CH2:22][CH2:23][CH3:24])(=[O:21])=[O:20].I[C:26]1[C:30]([C:31]2[CH:36]=[CH:35][N:34]=[C:33]([NH:37][CH2:38][C@@H:39]([NH:41][C:42](=[O:45])[O:43][CH3:44])[CH3:40])[N:32]=2)=[CH:29][N:28]([CH:46]([CH3:48])[CH3:47])[N:27]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[F:1][C:2]1[C:3]([NH:18][S:19]([CH2:22][CH2:23][CH3:24])(=[O:20])=[O:21])=[CH:4][CH:5]=[C:6]([F:17])[C:7]=1[C:26]1[C:30]([C:31]2[CH:36]=[CH:35][N:34]=[C:33]([NH:37][CH2:38][C@@H:39]([NH:41][C:42](=[O:45])[O:43][CH3:44])[CH3:40])[N:32]=2)=[CH:29][N:28]([CH:46]([CH3:48])[CH3:47])[N:27]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 51034342Methyl N-[(1S)-2-[[4-[3-iodo-1-(1-methylethyl)-1H-pyrazol-4-yl]-2-pyrimidinyl]amino]-1-methylethyl]carbamateHCID 51034690N-(2,4-difluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propane-1-sulfonamide

Product 1

HCID 51033681Methyl N-[(2S)-1-[(4-{3-[2,6-difluoro-3-(propane-1-sulfonamido)phenyl]-1-(propan-2-yl)-1H-pyrazol-4-yl}pyrimidin-2-yl)amino]propan-2-yl]carbamate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of crude Intermediate N-(2,4-difluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propane-1-sulfonamide (854 mg), Intermediate (S)-methyl 1-(4-(3-iodo-1-isopropyl-1H-pyrazol-4-yl)pyrimidin-2-ylamino)propan-2-ylcarbamate (350 mg, 90% pure), tetrakis(triphenylphosphine)palladium(0) (90 mg), 2 M aqueous sodium carbonate solution (6 ml), toluene (50 ml), and ethanol (6 ml) was heated at 80° C. for 16 h. The cooled mixture was extracted with ethyl acetate and the combined organic extracts were washed with brine. The organic phase was dried over sodium sulfate and concentrated. The crude product was purified by silica gel chromatography (70:1 to 40:1 DCM/methanol eluant) to provide the title compound.

Workup

  1. extractionThe cooled mixture was extracted with ethyl acetate
  2. washthe combined organic extracts were washed with brine
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography (70:1 to 40:1 DCM/methanol eluant)

Sources & evidence

ORD record
ord-7dce193b1a7a407fbc19b437aa0d852c
Source dataset
uspto-grants-2016_04
Patent number
US09314464B2

Reaction notes

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