1-Hydroxybenzotriazole → N-(3-[1,3]Dioxolan-2-yl-phenyl)-5-methyl-nicotinamide

HRID 1486740Notes

Reaction equation

HRID 1486740 reaction equation
CCN=C=NCCCN(C)C.Cl.[CH2:13]1[O:24][CH:16]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([NH2:23])[CH:18]=2)[O:15][CH2:14]1.[CH3:25][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([CH:34]=1)[C:31](O)=[O:32].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[O:24]1[CH2:13][CH2:14][O:15][CH:16]1[C:17]1[CH:18]=[C:19]([NH:23][C:31](=[O:32])[C:30]2[CH:34]=[C:26]([CH3:25])[CH:27]=[N:28][CH:29]=2)[CH:20]=[CH:21][CH:22]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2562085-Methylnicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 70203623-(1,3-Dioxolan-2-yl)aniline

Product 1

HCID 86706559N-(3-[1,3]Dioxolan-2-yl-phenyl)-5-methyl-nicotinamideYield 99%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

A solution of EDC hydrochloride (6.3 g, 32.81 mmol) in DCM (20 mL) is added over 5 min. to a solution of 3-aminobenzaldehyde ethylene acetal (3,614 g, 21.9 mmol), 5-methylnicotinic acid (3 g, 21.9 mmol), HOBt (6.7 g, 43.75 mmol), DMAP (534.5 mg, 4.38 mmol) and DIPEA (11.2 mL, 65.63 mmol) in DCM (30 mL) at RT under argon. The mixture is stirred at RT for 18 h. The mixture is diluted with DCM (50 mL) and washed twice with aq. sat. NaHCO3 (50 mL). The organic phase is separated and the aq. phase extracted twice with DCM (100 mL). The combined organic phases are washed with brine (200 mL), dried over MgSO4 and evaporated. The crude product is purified by flash chromatography on silica gel using a gradient of heptane and EtOAc 1:1 to heptane/EtOAc 1:4. After concentration of the product-containing fractions, the title compound (6.14 g, 99%) is obtained as a colorless solid LC-MS A: tR=0.58 min; [M+H]+=285.22.

Workup

  1. washwashed twice with aq. sat. NaHCO3 (50 mL)
  2. customThe organic phase is separated
  3. extractionthe aq. phase extracted twice with DCM (100 mL)
  4. washThe combined organic phases are washed with brine (200 mL)
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customThe crude product is purified by flash chromatography on silica gel using a gradient of heptane and EtOAc 1:1 to heptane/EtOAc 1:4

Sources & evidence

ORD record
ord-c65c9eadb0a04a54b145ffeef277bd3f
Source dataset
uspto-grants-2016_08
Patent number
US09428456B2

Reaction notes

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