Diisopropylethylamine → N-[2-(cyclopropylamino)-4,5-difluorophenyl]-5-(2-hydroxypropan-2-yl)pyridine-3-carboxamide

HRID 1048955Notes

Reaction equation

HRID 1048955 reaction equation
[CH:1]1([NH:4][C:5]2[C:6]([NH2:13])=[CH:7][C:8]([F:12])=[C:9]([F:11])[CH:10]=2)[CH2:3][CH2:2]1.[OH:14][C:15]([C:18]1[CH:19]=[C:20]([C:24](O)=[O:25])[CH:21]=[N:22][CH:23]=1)([CH3:17])[CH3:16].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>[CH:1]1([NH:4][C:5]2[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:6]=2[NH:13][C:24]([C:20]2[CH:21]=[N:22][CH:23]=[C:18]([C:15]([OH:14])([CH3:16])[CH3:17])[CH:19]=2)=[O:25])[CH2:3][CH2:2]1

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 68053726N1-cyclopropyl-4,5-difluorobenzene-1,2-diamineHCID 680538445-(2-Hydroxypropan-2-yl)nicotinic acid

Product 1

HCID 68053722N-[2-(cyclopropylamino)-4,5-difluorophenyl]-5-(2-hydroxypropan-2-yl)pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of the title compound from Step B (0.074 g, 0.40 mmol) in dichloromethane (2.1 mL) were added the title compound from Step C (0.080 g, 0.44 mmol), HATU (0.168 g, 0.442 mmol), HOAt (0.060 g, 0.44 mmol) and diisopropylethylamine (0.285 mL, 1.61 mmol). The reaction was stirred at room temperature for 1 hour, then diluted with dichloromethane, washed sequentially with water and brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel (50-100% ethyl acetate in hexanes) provided the title compound: LCMS m/z 330.04 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 8.96 (s, 1 H), 8.90 (d, J=7.2 Hz, 1 H), 8.35 (s, 1 H), 7.66 (br s, 1 H), 7.31 (d, J=10.7 Hz, 1 H), 7.04-7.00 (m, 1 H), 4.31 (br s, 1 H), 2.80 (br s, 1 H), 2.44 (t, J=6.1, 3.1 Hz, 1 H), 1.66 (s, 6 H), 0.78-0.77 (m, 2 H), 0.53-0.51 (m, 2 H).

Workup

  1. washwashed sequentially with water and brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash chromatography on silica gel (50-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-67869c524c534831b8c71adcaea120a1
Source dataset
uspto-grants-2016_07
Patent number
US09382226B2

Reaction notes

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