Triphenylphosphine → HCID 57791790, compound

HRID 1091721Notes

Reaction equation

HRID 1091721 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([OH:8])[CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[F:44][C:45]1[CH:62]=[CH:61][C:48]([CH2:49][C:50]2[C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[C:53](=[O:60])[NH:52][N:51]=2)=[CH:47][C:46]=1[C:63]([N:65]1[CH2:70][CH2:69][CH:68](O)[CH2:67][CH2:66]1)=[O:64]>C(Cl)Cl>[F:44][C:45]1[CH:62]=[CH:61][C:48]([CH2:49][C:50]2[C:59]3[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=3)[C:53](=[O:60])[NH:52][N:51]=2)=[CH:47][C:46]=1[C:63]([N:65]1[CH2:66][CH2:67][CH:68]([O:8][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[N:7]=2)[CH2:69][CH2:70]1)=[O:64]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 441993164-(4-fluoro-3-(4-hydroxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-oneHCID 178425782HCID 178425782, compound

Product 1

HCID 57791790HCID 57791790, compoundYield 7.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
20 °C

Procedure

6-methylpyridin-2-ol (95 mg, 0.87 mmol) was added in one portion to polymer supported triphenylphosphine (1.89 mmol/g; 460 mg, 0.87 mmol) in DCM (5 ml). Di-tert-butyl azodicarboxylate (201 mg, 0.87 mmol) and 4-(4-fluoro-3-(4-hydroxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one (2a) (111 mg, 0.29 mmol) in DCM (1 ml) was added and the resulting mixture was stirred at 20° C. for 4 hours. The reaction mixture was diluted with DCM and washed with water (×2). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by preparative HPLC (Waters XTerra C18 column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired material as a white solid (10 mg, 7.3% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.70-1.80 (1H, m), 1.85-1.95 (2H, m), 2.02-2.08 (1H, m), 2.41 (3H, s), 3.22-3.28 (1H, m), 3.51-3.57 (1H, m), 3.74-3.83 (1H, m), 3.95-4.03 (1H, m), 4.28 (2H, s), 5.32-5.35 (1H, m), 6.50 (1H, d), 6.69 (1H, d), 7.02 (1H, t), 7.26-7.29 (1H, m), 7.33-7.35 (1H, m), 7.44 (1H, t), 7.71-7.79 (3H, m), 8.45-8.48 (1H, m), 10.33 (1H, s); m/z (LC-MS, ESI+), RT=2.26 (M+H 473.6).

Workup

  1. washwashed with water (×2)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by preparative HPLC (Waters XTerra C18 column, 5μ silica, 19 mm diameter, 100 mm length)
  7. additionFractions containing the desired compound
  8. customwere evaporated to dryness

Sources & evidence

ORD record
ord-cf6a758a4cc7409d9acfd4cff4321c06
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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