3-Aminopyridine → (S)-1-(4-(4-(3-methylmorpholino)-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-3-yl)urea

HRID 707454Notes

Reaction equation

HRID 707454 reaction equation
Cl.[CH3:2][C@@H:3]1[N:8]([C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[S:21]([CH3:24])(=[O:23])=[O:22])[N:12]=[C:11]([C:25]3[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=3)[N:10]=2)[CH2:7][CH2:6][O:5][CH2:4]1.ClC(Cl)(O[C:36](=[O:42])OC(Cl)(Cl)Cl)Cl.[NH2:44][C:45]1[CH:46]=[N:47][CH:48]=[CH:49][CH:50]=1>C1COCC1.N1C=CC=CC=1>[CH3:2][C@@H:3]1[N:8]([C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[S:21]([CH3:24])(=[O:23])=[O:22])[N:12]=[C:11]([C:25]3[CH:26]=[CH:27][C:28]([NH:29][C:36]([NH:44][C:45]4[CH:46]=[N:47][CH:48]=[CH:49][CH:50]=4)=[O:42])=[CH:30][CH:31]=3)[N:10]=2)[CH2:7][CH2:6][O:5][CH2:4]1

Participants

5

Reactant 3

HCID 100093-AminopyridineHCID 94429TriphosgeneHCID 117761400(S)-4-(4-(3-methylmorpholino)-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)aniline hydrochloride

Product 1

HCID 71539166(S)-1-(4-(4-(3-methylmorpholino)-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-3-yl)urea

Reagents, catalysts & solvents 1

HCID 16069498Pyridine tetrahydrofuranSolvent2×

Procedure

To an ice cold solution of (S)-4-(4-(3-methylmorpholino)-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)aniline hydrochloride (0.217 g, 0.47 mmol) in THF/pyridine (4:1 respective ratio, 10 ml) was added triphosgene (1 eq) portionwise. The resulting suspension was stirred for five minutes before adding to an ice cold solution of 3-aminopyridine (4 eq) in THF/pyridine (4:1 respective ratio, 2 ml). The reaction was stirred at 0° C. for 1 hr after which time it was quenched by addition of methanol and concentrated in vacuo. The residue was purified by high pH preparative HPLC to afford the title compound, (S)-1-(4-(4-(3-methylmorpholino)-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-3-yl)urea, 24 mg, 38% yield. 1H NMR (400 MHz, MeOD) δ 8.63 (d, 1H), 8.38-8.33 (m, 2H), 8.19 (dd, 1H), 8.18-8.10 (m, 1H), 8.02 (ddd, 1H), 7.82 (td, 1H), 7.77-7.68 (m, 2H), 7.60-7.56 (m, 2H), 7.38 (dd, 1H), 5.17-4.37 (m, 2H), 3.99 (br s, 1H), 3.84-3.67 (m, 2H), 3.57 (t, 1H), 3.48 (s, 3H), 3.38 (dd, 1H), 1.39 (d, 3H);

Workup

  1. stirringThe reaction was stirred at 0° C. for 1 hr after which time it
  2. customwas quenched by addition of methanol
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by high pH preparative HPLC

Sources & evidence

ORD record
ord-9c5dbfd8aa7e4e6f829b0b75a5523250
Source dataset
uspto-grants-2015_11
Patent number
US09175011B2

Reaction notes

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