Dimethylformamide → 3-[4-(7-[2-(Trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedinitrile

HRID 40941Notes

Reaction equation

HRID 40941 reaction equation
[CH3:1][Si:2]([CH3:31])([CH3:30])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2[N:12]=[CH:13][N:14]=[C:15]([C:16]3[CH:17]=[N:18][N:19]([CH:21]([CH2:26][C:27]([NH2:29])=O)[CH2:22][C:23]([NH2:25])=O)[CH:20]=3)[C:10]=2[CH:9]=[CH:8]1.CN(C=O)C.ClC(Cl)(Cl)C(Cl)=O.CCCCCC>C(Cl)Cl>[CH3:31][Si:2]([CH3:1])([CH3:30])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2[N:12]=[CH:13][N:14]=[C:15]([C:16]3[CH:17]=[N:18][N:19]([CH:21]([CH2:26][C:27]#[N:29])[CH2:22][C:23]#[N:25])[CH:20]=3)[C:10]=2[CH:9]=[CH:8]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6420Trichloroacetyl chlorideHCID 8058HexaneHCID 574778763-[4-(7-[2-(Trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanediamide

Product 1

HCID 574778773-[4-(7-[2-(Trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedinitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

3-[4-(7-[2-(Trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanediamide (29.0 g, 0.0654 mol) was partially dissolved in DMF (200 mL, 2 mol), DCM (200 mL, 3 mol) and TEA (36 mL, 0.26 mol) and cooled in an ice bath under nitrogen atmosphere. The trichloroacetyl chloride (15 mL, 0.14 mol) was added dropwise turning the reaction to a dark solution. This was stirred at 0° C. for ½ h. The reaction was then concentrated to remove the DCM and the resulting DMF solution was diluted with water to precipitate the product. The solid precipitate was collected and washed with water to give a dark solid. The solid was then dissolved in DCM and washed with brine, dried over magnesium sulfate and concentrated to give a very dark oily residue. The residue was taken up in DCM, and hexane was added until the solution became slightly cloudy. This was stirred at rt to precipitate 3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedinitrile as white needle-like crystals (22.7 gm, 85%), LC /MS (M+H)+: 408, 1H NMR (DMSO-d6) δ 9.07(s, 1H), 8.87(s, 1H), 8.59(s, 1H), 7.88(d, 1H), 7.19(d, 1H), 5.75(s, 2H), 5.30(m,1H), 3.62(t, 2H), 3.40(m, 4H), 0.91(t, 2H), 0.10(s, 9H).

Workup

  1. customthe reaction to a dark solution
  2. concentrationThe reaction was then concentrated
  3. customto remove the DCM
  4. additionthe resulting DMF solution was diluted with water
  5. customto precipitate the product
  6. customThe solid precipitate was collected
  7. washwashed with water
  8. customto give a dark solid
  9. washwashed with brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated
  12. customto give a very dark oily residue
  13. stirringThis was stirred at rt
  14. customto precipitate 3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedinitrile as white needle-like crystals (22.7 gm, 85%), LC /MS (M+H)+

Sources & evidence

ORD record
ord-fb7ee31ece0944d78d2cba46754bbf98
Source dataset
uspto-grants-2013_09
Patent number
US08530485B2

Reaction notes

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