Acetonitrile → 3-[5-(diethoxymethyl)-3-thienyl]-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

HRID 40951Notes

Reaction equation

HRID 40951 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[C:7]3[CH:14]=[CH:13][N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:8]=3[N:9]=[CH:10][N:11]=2)[CH:3]=[N:2]1.C(#N)C.[CH2:26]([O:28][CH:29]([O:39][CH2:40][CH3:41])[C:30]1[S:34][CH:33]=[C:32](/[CH:35]=[CH:36]/[C:37]#[N:38])[CH:31]=1)[CH3:27].C1CCN2C(=NCCC2)CC1>O>[CH2:26]([O:28][CH:29]([O:39][CH2:40][CH3:41])[C:30]1[S:34][CH:33]=[C:32]([CH:35]([N:1]2[CH:5]=[C:4]([C:6]3[C:7]4[CH:14]=[CH:13][N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:8]=4[N:9]=[CH:10][N:11]=3)[CH:3]=[N:2]2)[CH2:36][C:37]#[N:38])[CH:31]=1)[CH3:27]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidineHCID 66597856(2E)-3-[5-(diethoxymethyl)-3-thienyl]acrylonitrile

Product 1

HCID 574778873-[5-(diethoxymethyl)-3-thienyl]-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrileYield 43.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 4-(1H-pyrazol-4-yl)-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidine (200 mg, 0.0007 mol) in ACN (2 mL, 0.04 mol) and (2E)-3-[5-(diethoxymethyl)-3-thienyl]acrylonitrile (160 mg, 0.00067 mol) (mixture of regioisomers) DBU (80 μL, 0.0005 mol) was added. The reaction was stirred overnight than water was added and the product was extracted with ethyl acetate. The combined extracts were washed with saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel eluting (50% EtOAc/Hexane) to give 3-[5-(diethoxymethyl)-3-thienyl]-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile (160 mg, 43%). 1H NMR (400 MHz, CDCl3): δ □8.92 (s, 1H), 8.41 (s, 1H), 8.29 (b, 1H), 7.45(d, 1H), 7.41(d, 1H), 7.15 (s, 1H), 7.05 (d, 1H), 6.82 (m, 1H), 5.74 (d, 2H), 3.74 (m, 2H), 3.71 (m, 8H), 3.59 (m, 1H), 1.32 (m, 4H), 0.95 (m, 2H), −0.08 (s, 9H); MS(ES):553 (M+1).

Workup

  1. additionwas added
  2. extractionthe product was extracted with ethyl acetate
  3. washThe combined extracts were washed with saturated sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash column chromatography on silica gel eluting (50% EtOAc/Hexane)

Sources & evidence

ORD record
ord-c4ba11cc8b484d36bf91d069d64cd6f0
Source dataset
uspto-grants-2013_09
Patent number
US08530485B2

Reaction notes

Loading…