Triphenylphosphine → tert-butyl 4-(4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylate

HRID 51614

Reaction equation

HRID 51614 reaction equation
[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.O[CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 5462977Diethyl azodicarboxylateHCID 148092816-Chloro-7-iodo-7-deazapurine

Product 1

HCID 22736256tert-butyl 4-(4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylateYield 47.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (6.48 g, 21.78 mmol) in tetrahydrofuran (200 mL) at 0° C. under a nitrogen atmosphere was treated with tert-butyl 4-hydroxy-1-piperidinecarboxylate (13.147 g, 65.33 mmol) and triphenylphosphine (11.43 g, 43.56 mmol) and stirred for 30 minutes. Diethylazodicarboxyate (7.61 g, 43.56 mmol) was added drop-wise over 15 minutes to the reaction solution. The ice bath was removed after 15 minutes, and the reaction mixture was allowed to stir over night. The solvent was evaporated under reduced pressure, and then the yellow gummy solid dissolved in dichloromethane. The solid precipitated was filtered and discarded. The filtrate was evaporated under reduced pressure. Recrystallization from ethyl acetate/heptane yielded 4.82 g (47%) of tert-butyl 4-(4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylate. 1H NMR (DMSO-d6, 400 MHz) 8.64(s, 1H), 8.20 (s, 1H), 4.89-4.84(m, 1H), 4.13-4.10 (m, 2H), 3.00-2.80(br s, 2H), 2.01-1.88 (m, 4H), 1.43(s, 9H). Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 m, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 7.825 minutes.

Workup

  1. customThe ice bath was removed after 15 minutes
  2. stirringto stir over night
  3. customThe solvent was evaporated under reduced pressure
  4. dissolutionthe yellow gummy solid dissolved in dichloromethane
  5. customThe solid precipitated
  6. filtrationwas filtered
  7. customThe filtrate was evaporated under reduced pressure
  8. customRecrystallization from ethyl acetate/heptane

Sources & evidence

ORD record
ord-16c14667cb0d4275929f86d61c359cd9
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Linked notes

Loading…