Acetic Anhydride → HCID 118005932, compound

HRID 1507319Notes

Reaction equation

HRID 1507319 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:12]([CH:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[OH:13])[CH:10]=2)[N:5]=[C:4]([O:20][CH3:21])[C:3]=1[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1.CCN(CC)CC.[C:40](OC(=O)C)(=[O:42])[CH3:41]>C(Cl)Cl>[C:40]([N:17]1[CH2:18][CH2:19][CH:14]([CH:12]([C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[N:5]=[C:4]([O:20][CH3:21])[C:3]([CH2:22][C:23]2[CH:24]=[CH:25][C:26]([C:29]([F:30])([F:32])[F:31])=[CH:27][CH:28]=2)=[C:2]3[Cl:1])[OH:13])[CH2:15][CH2:16]1)(=[O:42])[CH3:41]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 118005805HCID 118005805, compound2×

Product 1

HCID 118005932HCID 118005932, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(piperidin-4-yl)methanol (74 mg, 0.16 mmol, Intermediate 11: step b) in DCM (3 mL) was added Et3N (24 L, 0.18 mmol) and the resulting solution cooled to 0° C. Then acetic anhydride (16 μL, 0.17 mmol) was added dropwise and the reaction stirred at 0° C. for 30 minutes. The mixture was diluted with DCM and washed with saturated aqueous NaHCO3. The organic layer was dried (MgSO4), filtered, concentrated to dryness and purified by reverse-phase HPLC (acetonitrile/water+ TFA). The acidic fractions were neutralized by diluting with EtOAc and washing with saturated aqueous NaHCO3. The organics were concentrated to dryness, dissolved in 1/1 acetonitrile/water and lyophilized to provide the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.02-7.99 (m, 1H), 7.84-7.80 (m, 1H), 7.72-7.68 (m, 1H), 7.64 (d, J=8.0 Hz, 2H), 7.43 (d, J=7.9 Hz, 2H), 5.49 (s, 1H), 4.57-4.50 (m, 1H), 4.43-4.30 (m, 3H), 4.01 (s, 3H), 3.83-3.71 (m, 1H), 2.94-2.84 (m, 1H), 2.40-2.33 (m, 1H), 1.94 (d, J=8.2 Hz, 3H), 1.84-1.72 (m, 2H), 1.32-1.19 (m, 2H), 1.16-1.03 (m, 1H). MS (ESI): mass calcd. for C26H26ClF3N2O3, 506.2; m/z found, 507.1 [M+H]+.

Workup

  1. washwashed with saturated aqueous NaHCO3
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. custompurified by reverse-phase HPLC (acetonitrile/water+ TFA)
  6. additionby diluting with EtOAc
  7. washwashing with saturated aqueous NaHCO3
  8. concentrationThe organics were concentrated to dryness
  9. dissolutiondissolved in 1/1 acetonitrile/water

Sources & evidence

ORD record
ord-e3d825bcc92b4e26bbbe08ddcf14f1cf
Source dataset
uspto-grants-2015_12
Patent number
US09221804B2

Reaction notes

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