Ethyl Acetate → 1-(3,3-Dimethylbutyl)-3-(2-fluoro-5-(7-((4-methoxybenzyl)(methyl)amino)-2-methyl-1,6-naphthyridin-3-yl)phenyl)urea

HRID 715130Notes

Reaction equation

HRID 715130 reaction equation
C=C([O:4][C:5](=O)[NH:6][C:7]1[CH:12]=[C:11]([C:13]2[C:14]([CH3:34])=[N:15][C:16]3[C:21]([CH:22]=2)=[CH:20][N:19]=[C:18]([N:23]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[CH3:24])[CH:17]=3)[CH:10]=[CH:9][C:8]=1[F:35])C.[CH3:37][C:38]([CH3:43])([CH3:42])[CH2:39][CH2:40][NH2:41].C1CCN2C(=NCCC2)CC1.CCOC(C)=O>O1CCOCC1>[CH3:37][C:38]([CH3:43])([CH3:42])[CH2:39][CH2:40][NH:41][C:5]([NH:6][C:7]1[CH:12]=[C:11]([C:13]2[C:14]([CH3:34])=[N:15][C:16]3[C:21]([CH:22]=2)=[CH:20][N:19]=[C:18]([N:23]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=2)[CH3:24])[CH:17]=3)[CH:10]=[CH:9][C:8]=1[F:35])=[O:4]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 197093,3-DimethylbutylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 89827713Prop-1-en-2-yl(2-fluoro-5-(7-((4-methoxybenzyl)(methyl)amino)-2-methyl-1,6-naphthyridin-3-yl)phenyl)carbamate

Product 1

HCID 898143951-(3,3-Dimethylbutyl)-3-(2-fluoro-5-(7-((4-methoxybenzyl)(methyl)amino)-2-methyl-1,6-naphthyridin-3-yl)phenyl)ureaYield 85.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Treat a solution of prop-1-en-2-yl(2-fluoro-5-(7-((4-methoxybenzyl)(methyl)amino)-2-methyl-1,6-naphthyridin-3-yl)phenyl)carbamate (0.398 g, 0.818 mmol) and 3,3-dimethylbutylamine (0.166 g, 1.636 mmol) in dioxane (10 mL) with DBU (0.025 ml, 0.164 mmol) and heat at 80° C. overnight. Cool to RT, add EtOAc and wash with 10% LiCl, then brine. Dry the organic layer over MgSO4, concentrate to dryness and purify via silica gel chromatography (EtOAc/Hex) to afford the title compound (370 mg, 85%). 1H NMR (400 MHz, DMSO-d6): δ 8.97 (s, 1H), 8.37 (s, 1H), 8.22 (d, J=7.9 Hz, 1H), 7.99 (s, 1H), 7.26 (dd, J=11.4, 8.4 Hz, 1H), 7.15 (d, J=8.4 Hz, 2H), 6.98 (m, 1H), 6.85 (d, J=8.5 Hz, 2H), 6.73 (s, 1H), 6.55 (t, J=5.5 Hz, 1H), 4.86 (s, 2H), 3.69 (s, 3H), 3.08 (m, 5H), 2.48 (s, 3H), 1.33 (m, 2H), 0.88 (s, 9H); MS (ESI) m/z: 530.0 (M+H+).

Workup

  1. temperatureCool to RT
  2. washwash with 10% LiCl
  3. dry with materialDry the organic layer over MgSO4
  4. concentrationconcentrate to dryness
  5. custompurify via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-c319fd65b0064484a0fb1de952138ff8
Source dataset
uspto-grants-2015_11
Patent number
US09187474B2

Reaction notes

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