Sodium Carbonate → 5-[4-(benzyloxy)phenyl]-4-chloro-7-(1,4-dioxaspiro[4.5]dec-8-yl)-7H-pyrrolo[2,3-d]pyrimidine

HRID 51610Notes

Reaction equation

HRID 51610 reaction equation
[Cl:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([CH:12]3[CH2:21][CH2:20][C:15]4([O:19][CH2:18][CH2:17][O:16]4)[CH2:14][CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[CH2:22]([O:29][C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:22]([O:29][C:30]1[CH:35]=[CH:34][C:33]([C:10]2[C:3]3[C:2]([Cl:1])=[N:7][CH:6]=[N:5][C:4]=3[N:8]([CH:12]3[CH2:21][CH2:20][C:15]4([O:19][CH2:18][CH2:17][O:16]4)[CH2:14][CH2:13]3)[CH:9]=2)=[CH:32][CH:31]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343144-Benzyloxy-phenylboronic acidHCID 227363864-chloro-5-iodo-7-(1,4-dioxaspiro[4.5]decan-8-yl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 227363545-[4-(benzyloxy)phenyl]-4-chloro-7-(1,4-dioxaspiro[4.5]dec-8-yl)-7H-pyrrolo[2,3-d]pyrimidineYield 61%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-chloro-7-(1,4-dioxaspiro[4.5]dec-8-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (3.0 g, 7.15 mmol) in ethylene glycol dimethyl ether (100 mL) was treated with 4-(benzyloxy)phenylboronic acid (1.79 g, 7.87 mmol), tetrakis(triphenylphosphine)palladium (0.496 g, 0.429 mmol), and a solution of sodium carbonate (1.83 g, 17.16 mmol) in water (50 mL). A precipitate formed after 20 minutes. Reaction was stirred for 5 hours at 80° C. under a nitrogen atmosphere. The mixture was allowed to cool to room temperature and the organic solvent was removed under reduced pressure. The product was partitioned between the aqueous sodium carbonate layer and ethyl acetate. The aqueous layer was further extracted with ethyl acetate three times. The organic layers were combined, washed with water and brine, dried over magnesium sulfate, and partially concentrated until a precipitate formed. The solid was filtered, washed with ethyl acetate, and dried under a high vacuum. Yielded 2.06 g (61%) of 5-[4-(benzyloxy)phenyl]-4-chloro-7-(1,4-dioxaspiro[4.5]dec-8-yl)-7H-pyrrolo[2,3-d]pyrimidine. 1H NMR (DMSO-d6, 400 MHz) δ 8.64(s, 1H), 7.88(s, 1H), 7.52-7.33(m, 7H), 7.08-7.05(d, 2H, J=12 Hz), 5.15(s, 2H), 4.82-4.78 (m, 1H), 3.95-3.89(m, 4H), 2.21-2.13(m, 2H), 1.98-1.96(m, 2H), 1.85-1.75(m, 4H); Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 8.356 min.

Workup

  1. customA precipitate formed after 20 minutes
  2. customReaction
  3. temperatureto cool to room temperature
  4. customthe organic solvent was removed under reduced pressure
  5. customThe product was partitioned between the aqueous sodium carbonate layer and ethyl acetate
  6. extractionThe aqueous layer was further extracted with ethyl acetate three times
  7. washwashed with water and brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationpartially concentrated until a precipitate
  10. customformed
  11. filtrationThe solid was filtered
  12. washwashed with ethyl acetate
  13. customdried under a high vacuum

Sources & evidence

ORD record
ord-d74a51b4a91e47d69911f3e711c6116b
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Reaction notes

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