Acetonitrile → dimethyl 3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedioate

HRID 40939

Reaction equation

HRID 40939 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.C1CCN2C(=NCCC2)CC1.[C:37]([O:46][CH3:47])(=[O:45])/[CH:38]=[CH:39]/[CH2:40][C:41]([O:43][CH3:44])=[O:42]>C(OCC)(=O)C>[CH3:20][Si:19]([CH3:22])([CH3:21])[CH2:18][CH2:17][O:16][CH2:15][N:12]1[C:8]2[N:9]=[CH:10][N:11]=[C:6]([C:4]3[CH:5]=[N:1][N:2]([CH:39]([CH2:40][C:41]([O:43][CH3:44])=[O:42])[CH2:38][C:37]([O:46][CH3:47])=[O:45])[CH:3]=3)[C:7]=2[CH:14]=[CH:13]1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 5271579Dimethyl glutaconateHCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidine

Product 1

HCID 57477874dimethyl 3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedioateYield 64%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

4-(1H-Pyrazol-4-yl)-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidine (31.0 g, 0.0983 mol) was suspended in ACN (620 mL, 12 mol), and DBU (9.3 mL, 0.062 mol) was added under nitrogen. The reaction was heated to 65° C. and dimethyl (2E)-pent-2-enedioate (16 mL, 0.12 mol) was added in 5 mL portions over 2 h. After stirring overnight, the reaction was complete. The reaction was allowed to cool to room temperature and was concentrated in vacuo to give a dark oil. The oil was partitioned between ethyl acetate and water. The organic layer was washed with 1.0 N HCl, brine, dried over magnesium sulfate, and then concentrated to give a dark oil. The viscous oil was triturated with ethyl ether 3×500 mL to give a dark precipitate. The oil was taken up in ethyl acetate to form a solid. The solids were collected, washed with ethyl ether and dried to give dimethyl 3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedioate as a white powder (29.5 gm, 64%), LC/MS (M+H)+: 474, 1H NMR (DMSO-d6) δ 9.1 (s,1H), 9.02 (s,1H), 8.65 (s, 1H), 8.11 (d, 1H), 7.42(d, 1H), 5.78(s, 2H), 5.27(m, 1H), 3.65(m, 8H), 3.15(m, 4H), 0.95(t, 2H), 0.1(s, 9H).

Workup

  1. temperatureto cool to room temperature
  2. concentrationwas concentrated in vacuo
  3. customto give a dark oil
  4. customThe oil was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with 1.0 N HCl, brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customto give a dark oil
  9. customThe viscous oil was triturated with ethyl ether 3×500 mL
  10. customto give a dark precipitate
  11. customto form a solid
  12. customThe solids were collected
  13. washwashed with ethyl ether
  14. customdried

Sources & evidence

ORD record
ord-09d002c7f53143179ef829fed499f57e
Source dataset
uspto-grants-2013_09
Patent number
US08530485B2

Linked notes

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