Dimethylformamide → 3-Amino-6-(1,4-dioxaspiro[4.5]dec-8-yl)-N-methylpyridine-2-carboxamide

HRID 1948045Notes

Reaction equation

HRID 1948045 reaction equation
[NH2:1][C:2]1[C:3]([C:18](O)=[O:19])=[N:4][C:5]([CH:8]2[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH2:9]2)=[CH:6][CH:7]=1.[CH3:21][N:22](C=O)C.CCN(C(C)C)C(C)C.Cl.CN.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[NH2:1][C:2]1[C:3]([C:18]([NH:22][CH3:21])=[O:19])=[N:4][C:5]([CH:8]2[CH2:9][CH2:10][C:11]3([O:12][CH2:13][CH2:14][O:15]3)[CH2:16][CH2:17]2)=[CH:6][CH:7]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 6364545Methylamine hydrochlorideHCID 672534653-Amino-6-(1,4-dioxaspiro[4.5]dec-8-yl)pyridine-2-carboxylic acid2×

Product 1

HCID 672562083-Amino-6-(1,4-dioxaspiro[4.5]dec-8-yl)-N-methylpyridine-2-carboxamideYield 60.5%

Procedure

A solution of 3-amino-6-(1,4-dioxaspiro[4.5]dec-8-yl)pyridine-2-carboxylic acid (Compound 232D, 0.229 g, 0.823 mmol) in DMF (2.0 mL, 26 mmol) was cooled to 0° C. treated with DIPEA (2.87 mL, 16.4 mmol), methylamine hydrochloride (0.556 g, 8.23 mmol) and TBTU (0.396 g, 1.23 mmol). The flask was sealed and the mixture was allowed to come up to RT and stir overnight. The DMF and DIPEA were removed in vacuo and the residue was taken up in water and extracted multiple times with EtOAc and DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated to a yellow oil. This was purified on an ISCO Combiflash unit using 0-4% MeOH/DCM to isolate 145 mg of an oil. 1H NMR (400 MHz, DMSO-d6) δ 1.51-1.87 (m, 8H), 2.54-2.64 (m, 1H), 2.79 (d, J=4.80 Hz, 3H), 3.88 (s, 4H), 6.62 (s, 2H), 7.05-7.10 (m, 1H), 7.11-7.16 (m, 1H), 8.29 (d, J=4.55 Hz, 1H). MS (ES+): m/z=292.01 (100) [M+1]. HPLC: tR=3.31 min (ZQ3, polar—5 min).

Workup

  1. customThe flask was sealed
  2. customto come up to RT
  3. customThe DMF and DIPEA were removed in vacuo
  4. extractionextracted multiple times with EtOAc and DCM
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to a yellow oil
  8. customThis was purified on an ISCO Combiflash unit

Sources & evidence

ORD record
ord-8e541d1000cf42f1b2a772f63bf50fb7
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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