Dimethylformamide → HCID 58292876, compound

HRID 511385

Reaction equation

HRID 511385 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:13][C:14]2[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][N:17]=[C:16]([NH:24][C:25]3[CH:39]=[CH:38][C:28]([CH2:29][P:30](=[O:37])([O:34][CH2:35][CH3:36])[O:31][CH2:32][CH3:33])=[CH:27][CH:26]=3)[N:15]=2)=[C:6]2[C:10]=1[CH2:9][N:8]([CH3:11])[C:7]2=[O:12].[CH3:40][N:41](C=O)C>[C-]#N.[Zn+2].[C-]#N.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:40]([C:2]1[CH:3]=[CH:4][C:5]([NH:13][C:14]2[C:19]([C:20]([F:22])([F:21])[F:23])=[CH:18][N:17]=[C:16]([NH:24][C:25]3[CH:39]=[CH:38][C:28]([CH2:29][P:30](=[O:37])([O:31][CH2:32][CH3:33])[O:34][CH2:35][CH3:36])=[CH:27][CH:26]=3)[N:15]=2)=[C:6]2[C:10]=1[CH2:9][N:8]([CH3:11])[C:7]2=[O:12])#[N:41]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 58292897Diethyl [4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate

Product 1

HCID 58292876HCID 58292876, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

A mixture of diethyl [4-({4-[(7-bromo-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzyl]phosphonate (20.0 mg, 0.0318 mmol), zinc cyanide (3.74 mg, 0.0318 mmol), Pd(PPh3)4 (5.52 mg, 0.00477 mmol) in DMF (0.5 mL) was evacuated and purged with N2 three times. The mixture was irradiated in a microwave reactor at 150° C. for 5 minutes. The crude mixture was passed though a Thiol-SPE cartridge to remove Pd and subsequently purified by MDP. The title compound was obtained as white solid (13.5 mg, 74% yield). 1H NMR (400 MHz, CDCl3) δ=1.29 (t, J=7.1 Hz, 6 H), 3.20 (d, J=21.5 Hz, 2 H), 3.24 (s, 3 H), 4.09 (quin, J=7.3 Hz, 4 H), 4.54 (s, 2 H), 7.31-7.39 (m, 2 H), 7.49 (d, J=8.1 Hz, 2 H), 7.56 (br. s., 1 H), 7.70 (d, J=8.8 Hz, 1 H), 8.44 (s, 1 H), 8.70 (d, J=8.3 Hz, 1 H), 10.85 (s, 1 H). MS (ES+): m/z 575.21 (100) [MH+]; HPLC: tR=1.08 min (UPLC, purity).

Workup

  1. customwas evacuated
  2. custompurged with N2 three times
  3. customThe mixture was irradiated in a microwave reactor at 150° C. for 5 minutes
  4. customto remove Pd
  5. customsubsequently purified by MDP

Sources & evidence

ORD record
ord-4d132607e87045b88499aab66e5580f2
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Linked notes

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