Isopropanol → HCID 86700920, compound

HRID 625137Notes

Reaction equation

HRID 625137 reaction equation
[CH2:1]([O:8][C:9]1[C:14]2[CH:15]=[C:16]([C:18](=O)[CH2:19]Br)[O:17][C:13]=2[CH:12]=[C:11]([O:22][CH3:23])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:24][C@H:25]([C:27]1[S:31][C:30]([NH2:32])=[N:29][N:28]=1)[CH3:26].CC(O)C>C(Cl)Cl.C(#N)C>[CH2:1]([O:8][C:9]1[C:14]2[CH:15]=[C:16]([C:18]3[N:32]=[C:30]4[N:29]([CH:19]=3)[N:28]=[C:27]([C@@H:25]([F:24])[CH3:26])[S:31]4)[O:17][C:13]=2[CH:12]=[C:11]([O:22][CH3:23])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 3776IsopropanolHCID 86700919HCID 86700919, compoundHCID 86700921HCID 86700921, compound

Product 1

HCID 86700920HCID 86700920, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

In a 20 mL vial, 1-(4-(benzyloxy)-6-methoxybenzofuran-2-yl)-2-bromoethanone (Example 1E, 407 mg, 1.085 mmol) and (S)-5-(1-fluoroethyl)-1,3,4-thiadiazol-2-amine (Example 40A, 202 mg, 1.373 mmol) were suspended in 2-propanol (10 ml, 130 mmol) and heated at 80° C. for 18 h. After 5 min. the solution became homogeneous. A precipitate was present after overnight stirring. The cooled mixtures were transferred into 20 mL microwaves vials and then heated 30 min at 150° C. The mixtures were combined, diluted in CH2Cl2 (200 mL) and washed once with sat. NaHCO3, once with brine, dried over anh. Na2SO4 and concentrated. The residue was purified on ISCO using a REDISEP® Gold 40 g column (CH2Cl2/EtOAc). The crude product was adsorbed on SiO2. Fractions were collected and the orange solid obtained was tritured twice in ACN to give the title material a light yellow solid. LC (Method B): 2.403 min. MS (ESI) calcd. for C22H19FN3O3S [M+H]+ m/z: 424.1126; found: 424.1146. 1H NMR (400 MHz, DMSO-d6) d ppm 8.61 (s, 1H) 7.51 (d, J=7.4 Hz, 2H) 7.42 (t, J=7.6 Hz, 2H) 7.35 (t, J=7.0 Hz, 1H) 7.08 (s, 1H) 6.83-6.85 (m, 1H) 6.54 (d, J=1.2 Hz, 1H) 6.16 (dq, J=47.1, 6.4 Hz, 1H) 5.26 (s, 2H) 3.80 (s, 3H) 1.79 (dd, J=24.5, 6.8 Hz, 3H).

Workup

  1. waitA precipitate was present after overnight
  2. temperatureheated 30 min at 150° C
  3. washwashed once with sat. NaHCO3, once with brine
  4. dry with materialdried over anh. Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified on ISCO
  7. customFractions were collected
  8. customthe orange solid obtained

Sources & evidence

ORD record
ord-ef5d9ae46cd04ea989ebe4f4742a7157
Source dataset
uspto-grants-2016_04
Patent number
US09303065B2

Reaction notes

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