Diisopropylethylamine → 6-tert-butyl-N-(quinolin-4-ylmethyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-carboxamide

HRID 1697464Notes

Reaction equation

HRID 1697464 reaction equation
[C:1]([C:5]1[CH:17]=[CH:16][C:8]2[O:9][CH:10]([C:13]([OH:15])=O)[CH2:11][O:12][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[N:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]([CH2:28][NH2:29])=[CH:20][CH:19]=1.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C.O1CCCC1>[C:1]([C:5]1[CH:17]=[CH:16][C:8]2[O:9][CH:10]([C:13]([NH:29][CH2:28][C:21]3[C:22]4[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=4)[N:18]=[CH:19][CH:20]=3)=[O:15])[CH2:11][O:12][C:7]=2[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 6503896-tert-Butyl-2,3-dihydro-benzo[1,4]dioxine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12017326Quinolin-4-ylmethanamine

Product 1

HCID 441943916-tert-butyl-N-(quinolin-4-ylmethyl)-2,3-dihydrobenzo[b][1,4]dioxine-2-carboxamideYield 67.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-tert-Butyl-2,3-dihydro-benzo[1,4]dioxine-2-carboxylic acid (27 mg, 0.11 mmol), quinolin-4-yl-methanamine (15 mg, 0.09 mmol), and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (43 mg, 0.11 mmol) in DMF (0.4 mL) was added N,N-diisopropylethylamine (82 μL, 0.47 mmol). Tetrahydrofuran (0.8 mL) was added to dilute the solution. The reaction was left to stir overnight then concentrated and attempted purification by HPLC using 20-80% acetonitrile/water. Product isolated was less than 95% pure. It was purified again using 30-60% acetonitrile/water to obtain the product (23 mg, 64%) as a solid. m/z=376.8 (M+1)+. 1H-NMR (400 MHz, DMSO-d6) δ 8.89-8.81 (m, 1H), 8.76-8.72 (m, 1H), 8.16-8.13 (m, 1H), 8.04-8.02 (m, 1H), 7.80-7.75 (m, 1H), 7.66-7.61 (m, 1H), 7.11 (t, 1H, J=4.63 Hz), 6.93-6.89 (m, 2H), 4.99-4.95 (m, 1H), 4.93-4.73 (m, 2H), 4.41-4.28 (m, 2H), 1.24 (d, 9H, J=1.94 Hz).

Workup

  1. additionto dilute the solution
  2. waitThe reaction was left
  3. concentrationthen concentrated
  4. custompurification by HPLC
  5. customProduct isolated
  6. customIt was purified again

Sources & evidence

ORD record
ord-9b305e87d77940af8aff94b44db8a261
Source dataset
uspto-grants-2012_04
Patent number
US08163901B2

Reaction notes

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