Nitrogen → HCID 59441842, compound

HRID 1014516Notes

Reaction equation

HRID 1014516 reaction equation
N#N.Br[C:4]1[CH:13]=[CH:12][CH:11]=[C:10]([NH:14][C:15]2[C:16]3[CH:41]=[CH:40][N:39]([S:42]([C:45]4[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=4)(=[O:44])=[O:43])[C:17]=3[N:18]=[C:19]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([N:28]4[CH2:33][CH2:32][N:31]([CH:34]([CH3:36])[CH3:35])[CH2:30][CH2:29]4)=[CH:24][C:23]=3[O:37][CH3:38])[N:20]=2)[C:5]=1[C:6]([O:8][CH3:9])=[O:7].[CH3:52][N:53](C)C=O>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-]#N.[Zn+2].[C-]#N>[C:52]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]([NH:14][C:15]2[C:16]3[CH:41]=[CH:40][N:39]([S:42]([C:45]4[CH:46]=[CH:47][C:48]([CH3:51])=[CH:49][CH:50]=4)(=[O:44])=[O:43])[C:17]=3[N:18]=[C:19]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([N:28]4[CH2:33][CH2:32][N:31]([CH:34]([CH3:35])[CH3:36])[CH2:30][CH2:29]4)=[CH:24][C:23]=3[O:37][CH3:38])[N:20]=2)[C:5]=1[C:6]([O:8][CH3:9])=[O:7])#[N:53]

Participants

6

Reactant 3

HCID 947NitrogenHCID 6228DimethylformamideHCID 59442119HCID 59442119, compound

Product 1

HCID 59441842HCID 59441842, compoundYield 86%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

To a N2 degassed solution of methyl 2-bromo-6-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzoate (500 mg, 0.668 mmol) in N,N-Dimethylformamide (DMF) (10 ml) was added tetrakis(triphenylphosphine)palladium(0) (154 mg, 0.134 mmol) and zinc cyanide (94 mg, 0.801 mmol). The reaction was heated in the microwave at 120° C. for 10 min. The solvent was then removed, the residue redissolved in DCM (50 ml), washed with water (50 ml), adsorbed onto silica gel, and purified by silica gel chromatography (DCM to 5% MeOH/DCM) to afford methyl 2-cyano-6-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzoate (0.4 g, 86%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.01 (d, J=6.62 Hz, 6 H) 2.33 (s, 3 H) 2.57-2.64 (m, 4 H) 2.65-2.72 (m, 1 H) 3.09-3.18 (m, 4 H) 3.63 (s, 3 H) 3.83 (s, 3 H) 6.53-55 (m, 1 H) 6.64-6.66 (m, 1 H) 6.81 (d, J=4.01 Hz, 1 H) 7.36 (d, J=8.03 Hz, 2 H) 7.38 (d, J=4.01 Hz, 1 H) 7.52-7.57 (m, 1 H) 7.58-7.65 (m, 1 H) 7.71-7.74 (m, 1 H) 7.91 (d, J=8.23 Hz, 2 H) 7.95 (s, 1 H) 7.99-8.04 (m, 1 H) 9.95 (s, 1 H).

Workup

  1. customThe solvent was then removed
  2. dissolutionthe residue redissolved in DCM (50 ml)
  3. washwashed with water (50 ml)
  4. custompurified by silica gel chromatography (DCM to 5% MeOH/DCM)

Sources & evidence

ORD record
ord-e15ce30c6335406e8a68133136df9936
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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