Dimethylformamide → (S)-4-(5-cyano-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(isopropylcarbamoyl)phenyl)-2-methylpiperazine-1-carboxamide

HRID 1892136Notes

Reaction equation

HRID 1892136 reaction equation
Br[C:2]1[C:10]2[C:9]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([NH:19][C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26](=[O:31])[NH:27][CH:28]([CH3:30])[CH3:29])[CH:21]=4)=[O:18])[C@@H:13]([CH3:32])[CH2:12]3)=[N:8][CH:7]=[N:6][C:5]=2[N:4](S(C2C=CC=CC=2)(=O)=O)[CH:3]=1.[CH3:42][N:43](C=O)C>[C-]#N.[C-]#N.[Zn+2].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:42]([C:2]1[C:10]2[C:9]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([NH:19][C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26](=[O:31])[NH:27][CH:28]([CH3:30])[CH3:29])[CH:21]=4)=[O:18])[C@@H:13]([CH3:32])[CH2:12]3)=[N:8][CH:7]=[N:6][C:5]=2[NH:4][CH:3]=1)#[N:43]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 68728768(S)-4-(5-bromo-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(isopropylcarbamoyl)phenyl)-2-methylpiperazine-1-carboxamide

Product 1

HCID 57576308(S)-4-(5-cyano-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(isopropylcarbamoyl)phenyl)-2-methylpiperazine-1-carboxamide

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

To a solution of (S)-4-(5-bromo-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(isopropylcarbamoyl)-phenyl)-2-methylpiperazine-1-carboxamide from step D (70 mg, 0.11 mmol) in DMF (2 ml) was added Zn(CN)2 (26 mg, 0.22 mmol) and Pd(PPh3)4 (13 mg, 0.011 mmol). The mixture was heated at 150° C. for 3 min via microwave, cooled to room temperature, and filtered through a pad of celite. The solution was concentrated under vacuum, and the residue was treated with NaOH and MeOH for 2 hrs. The product was purified by Prep-HPLC to obtain (S)-4-(5-cyano-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-(3-(isopropylcarbamoyl)phenyl)-2-methylpiperazine-1-carboxamide as a white solid.

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through a pad of celite
  3. concentrationThe solution was concentrated under vacuum
  4. additionthe residue was treated with NaOH and MeOH for 2 hrs
  5. customThe product was purified by Prep-HPLC

Sources & evidence

ORD record
ord-4895b748b0a84ae2bec5ad731a65734c
Source dataset
uspto-grants-2013_08
Patent number
US08507672B2

Reaction notes

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