Sodium hydride → tert-butyl4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-piperidinecarboxylate

HRID 51523Notes

Reaction equation

HRID 51523 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[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]2)(=O)=O)=CC=1>CN(C=O)C>[C:46]([O:45][C:43]([N:40]1[CH2:41][CH2:42][CH:37]([N:8]2[C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[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]2)[CH2:38][CH2:39]1)=[O:44])([CH3:49])([CH3:47])[CH3:48]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 120422345-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamineHCID 157347131-(tert-Butoxycarbonyl)-4-(p-toluenesulfonyloxy)piperidine

Product 1

HCID 22736379tert-butyl4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-piperidinecarboxylateYield 31.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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 (100 ml) under nitrogen at 0° C. was added NaH (0.264 g, 60% dispersion, 6.6 mmol) and the reaction mixture warmed to room temperature and stirred for 1 hr. Tert-butyl 4-[(4-methylphenyl)sulfonyl]oxy-1-piperidinecarboxylate (2.34 g, 6.6 mmol) was added and the resulting solution heated at 95° C. for 72 hr. The reaction was quenched by careful addition of water (150 ml). Extract with EtOAc (3×100 ml) and wash with water (4×100 ml) and brine (2×100 ml). The organic solution was dried (Na2SO4), filtered and evaporated to leave a solid which was adsorbed onto silica and purified by flash silica gel column chromatography using EtOAc then 5% MeOH/EtOAc as eluent to give in F 13-22 tert-butyl4-[4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-1-piperidinecarboxylate (1.0 g, 31%) as a white solid, m.pt. 168.5-169.5° C. Rf in 10% EtOAc/MeOH=0.4. 1H NMR (d6 DMSO, 250 MHz): δ 8.14 (1H, s), 7.38-7.49 (5H, m), 7.07-7.23 (5H, m), 6.14 (2H, bs), 4.76 (1H, m), 4.11 (2H, m), 2.93 (2H, m), 1.92-2.02 (4H, m), 1.43 (9H, s). Mass spec. C28H31O3N5 (485.2430). IR (KBr disc): 3059, 1695, 1588, 1235 cm−1.

Workup

  1. temperaturethe resulting solution heated at 95° C. for 72 hr
  2. customThe reaction was quenched by careful addition of water (150 ml)
  3. extractionExtract with EtOAc (3×100 ml)
  4. washwash with water (4×100 ml) and brine (2×100 ml)
  5. dry with materialThe organic solution was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto leave a solid which
  9. custompurified by flash silica gel column chromatography

Sources & evidence

ORD record
ord-26c8c208795f4595aee865656e474d21
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Reaction notes

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