Diisopropylethylamine → 5-acetyl-N-[2-(cyclopropylamino)-4-fluorophenyl]pyridine-3-carboxamide

HRID 1048959Notes

Reaction equation

HRID 1048959 reaction equation
[CH:1]1([NH:4][C:5]2[C:6]([NH2:12])=[CH:7][CH:8]=[C:9]([F:11])[CH:10]=2)[CH2:3][CH2:2]1.[C:13]([C:16]1[CH:17]=[C:18]([C:22](O)=[O:23])[CH:19]=[N:20][CH:21]=1)(=[O:15])[CH3:14].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=NC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>ClCCl>[C:13]([C:16]1[CH:17]=[C:18]([C:22]([NH:12][C:6]2[CH:7]=[CH:8][C:9]([F:11])=[CH:10][C:5]=2[NH:4][CH:1]2[CH2:3][CH2:2]2)=[O:23])[CH:19]=[N:20][CH:21]=1)(=[O:15])[CH3:14]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 218549245-Acetylpyridine-3-carboxylic acidHCID 545925541-N-cyclopropyl-5-fluorobenzene-1,2-diamine

Product 1

HCID 680534385-acetyl-N-[2-(cyclopropylamino)-4-fluorophenyl]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N2-cyclopropyl-4-fluorobenzene-1,2-diamine (0.082 g, 0.495 mmol) in dichloromethane were added the title compound from Step A (0.090 g, 0.545 mmol), HATU (0.207 g, 0.545 mmol), HOAt (0.074 g, 0.545 mmol), and diisopropylethylamine (0.35 mL, 1.98 mmol). The reaction was stirred at room temperature for 1 hour, then diluted with dichloromethane, washed with water and brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica gel (30-60% ethyl acetate in hexanes) provided the title compound: LCMS m/z 314.14 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.33 (s, 1 H), 9.29 (s, 1 H), 8.72 (s, 1 H), 8.02 (br s, 1 H), 7.19-7.16 (m, 1 H), 6.91 (d, J=10.5 Hz, 1 H), 6.50-6.47 (m, 1 H), 4.64 (br s, 1 H), 2.69 (s, 3 H), 2.45-2.44 (m, 1 H), 0.78-0.77 (m, 2 H), 0.52-0.51 (m, 2 H).

Workup

  1. washwashed with water and brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica gel (30-60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-8d869e2f4fca4535b8634dfe16746458
Source dataset
uspto-grants-2016_07
Patent number
US09382226B2

Reaction notes

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