Dichloromethane → Cevidoplenib

HRID 1503351Notes

Reaction equation

HRID 1503351 reaction equation
[CH3:1][C:2]1[C:6](CO)=[CH:5][N:4]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[N:21]([CH3:25])[CH:20]=[CH:19]4)[N:10]=2)[N:3]=1.Cl.[O:27]1[CH2:31][C@@H:30]([OH:32])[CH2:29][NH:28]1.[CH2:33](N(CC)CC)[CH3:34].[BH-](O[C:50]([CH3:52])=[O:51])(OC(C)=O)OC(C)=O.[Na+].Cl[CH2:55]Cl>CN(C)C(=O)C>[CH:52]1([C:50]([C:19]2[C:18]3[C:22](=[CH:23][CH:24]=[C:16]([NH:15][C:11]4[N:10]=[C:9]([N:4]5[CH:5]=[C:6]([CH2:55][N:28]6[CH2:29][C@H:30]([OH:32])[CH2:31][O:27]6)[C:2]([CH3:1])=[N:3]5)[CH:14]=[CH:13][N:12]=4)[CH:17]=3)[N:21]([CH3:25])[CH:20]=2)=[O:51])[CH2:34][CH2:33]1

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 66855047(4S)-1,2-oxazolidin-4-ol hydrochlorideHCID 86698985(3-methyl-1-(2-(1-methyl-1H-indol-5-ylamino)pyrimidin-4-yl)-1H-pyrazol-4-yl)methanol

Product 1

HCID 91754477CevidoplenibYield 50%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a slurry of intermediate 2 (500 mg, 1.14 mmol), (S)-isoxazolidin-4-ol hydrochloride (220 mg, Tetrahedron Lett., 2006, 47, 7635-7639) and triethylamine (0.79 mL) in 10 mL of dichloromethane and 10 mL of N,N-dimethylacetamide (DMAC), was added NaBH(OAc)3 (730 mg, 3.42 mmol) at room temperature. Volatiles were removed in vacuo. It was extracted with dichloromethane (×3). The collected organic layers were dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting residue was purified by silica gel chromatography (DCM/MeOH) to give 270 mg (50%) of the desired compound 1 as a pale yellow solid; MS (ESI) m/z 474 [M+H]+, 1H NMR (300 MHz, DMSO-d6) δ 9.85 (s, 1H), 9.30 (s, 1H), 9.02 (s, 1H), 8.48 (d, J=5.4 Hz, 1H), 7.47 (d, J=9.0 Hz, 1H), 7.36 (d, J=8.7 Hz, 1H), 7.13 (d, J=5.4 Hz, 1H), 5.19 (s, 1H), 4.60 (d, 1H), 4.10 (m, 1H), 3.94 (d, 2H), 3.87 (s, 3H), 3.81 (m, 1H), 2.86 (m, 1H), 2.65 (m, 1H), 2.29 (s, 1H), 0.92 (d, J=6.0 Hz, 2H).

Workup

  1. customVolatiles were removed in vacuo
  2. extractionIt was extracted with dichloromethane (×3)
  3. dry with materialThe collected organic layers were dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by silica gel chromatography (DCM/MeOH)

Sources & evidence

ORD record
ord-786d563e92c14873af68b4206ce36901
Source dataset
uspto-grants-2015_12
Patent number
US09212178B2

Reaction notes

Loading…