Sodium hydride → HCID 22736315, compound

HRID 51527Notes

Reaction equation

HRID 51527 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[H-].[Na+].CC1C=CC(S(O[CH:37]2[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38]2)(=O)=O)=CC=1>CN(C=O)C.CCOC(C)=O.CO>[NH2:1][C:2]1[C:3]2[C:10]([C:11]3[CH:12]=[CH:13][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:15][CH:16]=3)=[CH:9][N:8]([CH:41]3[CH2:37][CH2:38][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:40]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 120422345-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamineHCID 13591085tert-Butyl 3-(tosyloxy)pyrrolidine-1-carboxylate

Product 1

HCID 22736315HCID 22736315, compoundYield 32.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

To a solution of 4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine (2.0 g, 6.6 mmol) in dry DMF (120 ml) under nitrogen at 0° C. was added NaH (0.264 g, 60% dispeersion, 6.6 mmol) and then reaction mixture warmed to room temperature and stirred for 1 hr. tert-butyl 3-[(4-methylphenyl)sulfonyl]oxy-1-pyrrolidinecarboxylate (2.25 g, 6.6 mmol) was added portionwise and the mixture heated at 95° C. for 72 hr. Quench with water and extract with EtOAc (4×100 ml). Wash the combined organic solutions with water (4×100 ml) and brine (2×100 ml). The organics were dried (sodium sulphate), filtered and evaporated to leave a solid which was dissolved in EtOAc/MeOH and adsorbed onto silica. Purification using flash silica gel column chromatography with 5% MeOH/EtOAc as eluent gave in F 17-25 tert-butyl 3-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-pyrrolidinecarboxylate (1.0 g, 32%) as a white solid m.pt. 168-170° C. Rf in 9:1 EtOAc: MeOH=0.46. 1H NMR (d6 DMSO, 250 MHz): 8.17 (1H, s), 7.38-7.50 (5H, m), 6.19 (2H, bs), 5.31 (1H, m), 3.77 (1H, m), 3.42-3.60 (3H, m), 2.38 (2H, m), 1.40 (9H, s). Mass spec. 471.2250 (C27H29O3N5) IR (KBr disc): 3130, 1683, 1585, 1404, 1245 cm−1.

Workup

  1. customreaction mixture
  2. temperaturethe mixture heated at 95° C. for 72 hr
  3. customQuench with water
  4. extractionextract with EtOAc (4×100 ml)
  5. washWash the combined organic solutions with water (4×100 ml) and brine (2×100 ml)
  6. dry with materialThe organics were dried (sodium sulphate)
  7. filtrationfiltered
  8. customevaporated
  9. customto leave a solid which
  10. customPurification

Sources & evidence

ORD record
ord-a89e829395c94bd09e726eadfb5f76b8
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Reaction notes

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