Triphenylphosphine → HCID 57791787, compound

HRID 1091701Notes

Reaction equation

HRID 1091701 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[F:10][C:11]1[CH:28]=[CH:27][C:14]([CH2:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19](=[O:26])[NH:18][N:17]=2)=[CH:13][C:12]=1[C:29]([N:31]1[CH2:36][CH2:35][CH:34](O)[CH2:33][CH2:32]1)=[O:30].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>ClCCl>[F:10][C:11]1[CH:28]=[CH:27][C:14]([CH2:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19](=[O:26])[NH:18][N:17]=2)=[CH:13][C:12]=1[C:29]([N:31]1[CH2:32][CH2:33][CH:34]([O:1][C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=2)[CH2:35][CH2:36]1)=[O:30]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 130194-CyanophenolHCID 97268Di-tert-butyl azodicarboxylateHCID 441993164-(4-fluoro-3-(4-hydroxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one

Product 1

HCID 57791787HCID 57791787, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-hydroxybenzonitrile (48 mg, 0.40 mmol) and 4-(4-fluoro-3-(4-hydroxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one (2a) (150 mg, 0.39 mmol) in dichloromethane (5 mL) was treated with polymer supported triphenylphosphine (ex-Biotage, 742 mg, 1.37 mmol) and di-tert-butyl azodicarboxylate (300 mg, 1.30 mmol). The reaction mixture was agitated at ambient temperature for 4-5 hours. Mixture was then filtered to remove resin, and filter cake washed through with methanol. Filtrate was evaporated to afford a waxy yellow solid, which was purified by repeated preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), firstly using decreasingly polar mixtures of water (containing 0.1% TFA) and MeCN as eluents, then using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents (Waters Sunfire Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length). Fractions containing the desired compound were evaporated to dryness and lyophilised to afford the desired product (17 mg, 8% yield); 1H NMR (400.132 MHz, DMSO) δ 1.49-1.69 (2H, m), 1.83-1.91 (1H, m), 1.99-2.06 (1H, m), 3.14-3.22 (1H, m), 3.32-3.51 (2H, m), 3.94-4.04 (1H, m), 4.33 (2H, s), 4.78-4.84 (1H, m), 7.15-7.18 (2H, m), 7.23 (1H, t), 7.36-7.44 (2H, m), 7.75-7.78 (2H, m), 7.80-7.90 (2H, m), 7.97 (1H, d), 8.26 (1H, d), 12.56 (1H, s); m/z (LC-MS, ESI+), RT=2.20 (M+H 483.6).

Workup

  1. filtrationMixture was then filtered
  2. customto remove resin
  3. filtrationfilter cake
  4. washwashed through with methanol
  5. customFiltrate was evaporated
  6. customto afford a waxy yellow solid, which
  7. customwas purified
  8. additionFractions containing the desired compound
  9. customwere evaporated to dryness

Sources & evidence

ORD record
ord-c619bab462d040e195edf296aa6b12bd
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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