Triphenylphosphine → (S)-6,8-dichloro-2,3,3a,4-tetrahydro-1H-5-oxa-7,9,9b-triaza-cyclopenta[a]naphthalene

HRID 334144Notes

Reaction equation

HRID 334144 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[Cl:15][C:16]1[N:21]=[C:20]([Cl:22])[C:19](O)=[C:18]([N:24]2[CH2:28][CH2:27][CH2:26][C@H:25]2[CH2:29][OH:30])[N:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1>[Cl:22][C:20]1[N:21]=[C:16]([Cl:15])[N:17]=[C:18]2[C:19]=1[O:30][CH2:29][C@@H:25]1[CH2:26][CH2:27][CH2:28][N:24]12

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 866673612,4-dichloro-6-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-pyrimidin-5-ol

Product 1

HCID 86667362(S)-6,8-dichloro-2,3,3a,4-tetrahydro-1H-5-oxa-7,9,9b-triaza-cyclopenta[a]naphthalene

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of [(S)-1-(2,6-dichloro-5-methoxy-pyrimidin-4-yl)-pyrrolidin-2-yl]-methanol (900 mg, 3.24 mmol) and lithium chloride (360 mg, 8.48 mmol) in anhydrous DMF (10 mL) was heated at 160° C. for 10 mins in a microwave reactor, then concentrated in vacuo to give 2,4-dichloro-6-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-pyrimidin-5-ol. DIAD (700 μL, 3.56 mmol) was added to a solution of 2,4-dichloro-6-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-pyrimidin-5-ol (3 mmol) and triphenyl phosphine (900 mg, 3.43 mmol) in 1,4-dioxane (10 mL) and the mixture stirred at RT for 1 h, then concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, 0 to 20% ethyl acetate in cyclohexane) affording (S)-6,8-dichloro-2,3,3a,4-tetrahydro-1H-5-oxa-7,9,9b-triaza-cyclopenta[a]naphthalene. LCMS (method A): RT=2.98 min, [M+H]−=246/248.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe resulting residue was purified by column chromatography (SiO2, 0 to 20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-070d77b4a6714b93864525bb724bc29c
Source dataset
uspto-grants-2014_11
Patent number
US08883799B2

Reaction notes

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