Tributylphosphine → HCID 86700913, compound

HRID 1424369Notes

Reaction equation

HRID 1424369 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[O:8][C:7]([C:9]3[N:10]=[C:11]4[N:15]([CH:16]=3)[N:14]=[C:13]([O:17][CH3:18])[S:12]4)=[CH:6][C:5]2=[C:19]([OH:21])[CH:20]=1.[C:22]1([C:28]2[S:29][CH:30]=[C:31]([CH2:33]O)[N:32]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(P(CCCC)CCCC)CCC.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:20]=[C:19]([O:21][CH2:33][C:31]2[N:32]=[C:28]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[S:29][CH:30]=2)[C:5]2[CH:6]=[C:7]([C:9]3[N:10]=[C:11]4[N:15]([CH:16]=3)[N:14]=[C:13]([O:17][CH3:18])[S:12]4)[O:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 27764734-(Hydroxymethyl)-2-phenyl-1,3-thiazoleHCID 86700912HCID 86700912, compound

Product 1

HCID 86700913HCID 86700913, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A flame-dried 100 mL round-bottom flask containing 6-chloro-2-(2-methoxyimidazo[2,1-b][1,3,4]thiadiazol-6-yl)benzofuran-4-ol (Example 37I, 25 mgs, 0.078 mmol) and (2-phenylthiazol-4-yl)methanol (Example 3B, 37.2 mgs, 0.194 mmol) in dry THF (4 mL) was added tributylphosphine (0.050 mL, 0.194 mmol). The resulting solution was charged with a solution of ADDP (49.0 mgs, 0.194 mmol) in THF (1 mL) added dropwise over 30 minutes via syringe pump. After stirring for 1.5 hours the reaction mixture was diluted with EtOAc then washed with 1N HCl, sat. NaHCO3, water and brine. The organic phase was dried (MgSO4) then concentrated to dryness. The residue was purified by ISCO using 0 to 10% diethyl ether in DCM. Fractions containing the desired product were concentrated to give the title material as a beige solid (20 mgs, 0.040 mmol, 52.0% yield). LC (Method A): 2.534 min. LCMS (APCI) calcd for C23H16ClN4O3S2 [M+H]+ m/z 495.03. found 495.0. 1H NMR (CDCl3, 400 MHz) δ ppm: 8.49 (s, 1H), 7.99-7.96 (m, 2H), 7.93 (s, 1H), 7.55-7.50 (m, 3H), 7.40 (dd, J=0.8, 1.6 Hz, 1H), 7.15 (dd, J=0.4, 1.6 Hz, 1H), 7.14 (d, J=0.8 Hz, 1H), 5.43 (s, 2H), 4.21 (s, 3H).

Workup

  1. additionadded dropwise over 30 minutes via syringe pump
  2. washthen washed with 1N HCl, sat. NaHCO3, water and brine
  3. dry with materialThe organic phase was dried (MgSO4)
  4. concentrationthen concentrated to dryness
  5. customThe residue was purified by ISCO
  6. additionFractions containing the desired product
  7. concentrationwere concentrated

Sources & evidence

ORD record
ord-e440d8f2dfa2491ebf8a91b06aa8a8d2
Source dataset
uspto-grants-2015_01
Patent number
US08927688B2

Reaction notes

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