Triphenylphosphine → 5-bromo-4-chloro-7-[2-(4-morpholinyl)ethyl]-7H-pyrrolo[2,3-d]pyrimidine

HRID 1910025Notes

Reaction equation

HRID 1910025 reaction equation
[Br:1][C:2]1[C:10]2[C:5]([NH:6][CH:7]=[N:8][C:9]=2[Cl:11])=[N:4][CH:3]=1.[N:12]1([CH2:18][CH2:19]O)[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[Br:1][C:2]1[C:10]2[C:9]([Cl:11])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH2:19][CH2:18][N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 611632-MorpholinoethanolHCID 5462977Diethyl azodicarboxylateHCID 178478408HCID 178478408, compound

Product 1

HCID 866636825-bromo-4-chloro-7-[2-(4-morpholinyl)ethyl]-7H-pyrrolo[2,3-d]pyrimidineYield 82.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 5-bromo-4-chloro-1H-pyrrolo[2,3-d]pyrimidine (200 mg, 0.860 mmol), 2-(4-morpholinyl)ethanol (0.316 mL, 2.58 mmol) and triphenylphosphine (451 mg, 1.721 mmol) was added Tetrahydrofuran (THF) (5 mL). To the reaction was then added by dropwise DEAD (0.272 mL, 1.721 mmol). The solution was then let stir overnight at room temperature. The reaction was then concentrated and diluted with water (10 ml) then extracted by EtOAc (3×10 ml). The organics were combined, washed with brine, dried over MgSO4, filtered and concentrated. The yellow crude residue was then loaded onto a 25 g Biotage SNAP column and purified with 0 to 8% MeOH in DCM gradient over 30 minutes to afford 5-bromo-4-chloro-7-[2-(4-morpholinyl)ethyl]-7H-pyrrolo[2,3-d]pyrimidine (245 mg, 82% yield) as a light yellow solid. LC-MS (ES) m/z=347.2 [M+H]+1H NMR (400 MHz, DMSO-d6) δ 8.67 (s, 1H), 8.05 (s, 1H), 4.39 (t, J=6.19 Hz, 2H), 3.48 (t, J=4.29 Hz, 4H), 2.71 (t, J=6.32 Hz, 2H), 2.42 (br. s., 4H).

Workup

  1. concentrationThe reaction was then concentrated
  2. additiondiluted with water (10 ml)
  3. extractionthen extracted by EtOAc (3×10 ml)
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified with 0 to 8% MeOH in DCM gradient over 30 minutes

Sources & evidence

ORD record
ord-14041ea8140b431699d5ec0c2b0b4366
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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