Pivaloyl chloride → HCID 68773954, compound

HRID 1947535Notes

Reaction equation

HRID 1947535 reaction equation
Cl.[S:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[C:3]1[O:11][C:12]1[CH:27]=[CH:26][C:15]2[CH:16]=[C:17]([CH2:19][N:20]3[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21]3)[O:18][C:14]=2[CH:13]=1.CCN(C(C)C)C(C)C.[C:37](Cl)(=[O:42])[C:38]([CH3:41])([CH3:40])[CH3:39]>C(Cl)Cl>[CH:14]([OH:18])=[O:42].[CH3:39][C:38]([CH3:41])([CH3:40])[C:37]([NH:25][CH:22]1[CH2:23][CH2:24][N:20]([CH2:19][C:17]2[O:18][C:14]3[CH:13]=[C:12]([O:11][C:3]4[S:2][C:10]5[C:5]([N:4]=4)=[N:6][CH:7]=[CH:8][CH:9]=5)[CH:27]=[CH:26][C:15]=3[CH:16]=2)[CH2:21]1)=[O:42]

Participants

5

Reactant 3

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 68770609HCID 68770609, compound

Product 1

HCID 68773954HCID 68773954, compoundYield 80.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-[6-(thiazolo[4,5-b]pyridin-2-yloxy)-benzofuran-2-ylmethyl]-pyrrolidin-3-ylamine hydrochloride (65 mg, 0.161 mmol) in DCM (2 mL) was added DIEA (64 μL, 0.484 mmol) followed by pivaloyl chloride (20 μL, 0.484 mmol) and the resulting solution was stirred (rt, 1 h). The reaction mixture was partitioned with DCM (5 mL) and saturated NaHCO3 (5 mL). The layers were separated and the aqueous layer was extracted with DCM (3×10 mL). The organic layers were combined, dried, filtered and concentrated in vacuo. The resulting residue was purified by flash column chromatography using MeOH:DCM (0-10%) followed by reverse phase HPLC to provide the title compound as a yellow solid (32 mg, 40%). MS (ESI): mass calcd. for C24H26N4O3S, 450.2; m/z found, 451.0 [M+H]+. 1H NMR (500 MHz, CD3OD): 8.48 (dd, J=4.8, 1.3, 1H), 8.30 (dd, J=8.0, 1.6, 2H), 7.72-7.68 (m, 2H), 7.38-7.29 (m, 2H), 6.92 (s, 1H), 4.47-4.37 (m, 1H), 4.13-4.02 (m, 2H), 3.19-3.04 (m, 2H), 2.89-2.75 (m, 2H), 2.38-2.30 (m, 1H), 1.84-1.77 (m, 1H), 1.16 (s, 9H).

Workup

  1. customThe reaction mixture was partitioned with DCM (5 mL) and saturated NaHCO3 (5 mL)
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with DCM (3×10 mL)
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-585574785c2e4872942e997d127c83a7
Source dataset
uspto-grants-2013_03
Patent number
US08399465B2

Reaction notes

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