4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → HCID 89462032, compound

HRID 931663Notes

Reaction equation

HRID 931663 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:20]=[C:19]([F:21])[C:18]3[O:17][C:16]4[C:11](=[CH:12][C:13]([NH2:22])=[CH:14][CH:15]=4)[C@@:10]4([CH2:27][CH2:26][O:25][C:24]([NH2:28])=[N:23]4)[C:9]=3[CH:8]=2)[CH2:3][CH2:2]1.[CH3:29][O:30][C:31]1[N:32]=[CH:33][C:34]([C:37](O)=[O:38])=[N:35][CH:36]=1.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CO>[NH2:28][C:24]1[O:25][CH2:26][CH2:27][C@@:10]2([N:23]=1)[C:9]1[CH:8]=[C:7]([C:4]3[CH2:3][CH2:2][O:1][CH2:6][CH:5]=3)[CH:20]=[C:19]([F:21])[C:18]=1[O:17][C:16]1[C:11]2=[CH:12][C:13]([NH:22][C:37]([C:34]2[CH:33]=[N:32][C:31]([O:30][CH3:29])=[CH:36][N:35]=2)=[O:38])=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 457898115-Methoxy-2-pyrazinecarboxylic acidHCID 117600815HCID 117600815, compound

Product 1

HCID 89462032HCID 89462032, compoundYield 53.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The (S)-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthene]-2,7′-diamine (0.048 g, 0.126 mmol) was suspended in MeOH (2.5 mL). The 5-methoxypyrazine-2-carboxylic acid (0.019 g, 0.126 mmol) was added, followed by 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride (0.035 g, 0.126 mmol). After 30 min another 1 mg of the acid (0.05 equiv) and 1.75 mg of the coupling agent (0.05 equiv) were added. After 2 h, the reaction was quenched with 15 mL of half-saturated NaHCO3. The material was extracted with 5% MeOH-dcm (3×25 mL). The organics were combined, washed with dilute brine (8 mL), dried over MgSO4 and concentrated. The material was purified through silica gel (35 mL) using 10% to 20% EtOH in 2:1 hexane-EtOAc, affording (S)—N-(2-amino-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-7′-yl)-5-methoxypyrazine-2-carboxamide (35 mg, 0.067 mmol). MS m/z=518 [M+H]−1. 1H NMR in CDCl3 δ: 9.52 (s, 1H), 9.03 (s, 1H), 8.16 (s, 1H), 7.76 (dd, 1H, J=8.7, 2.4), 7.66 (d, 1H, J=2.5), 7.01 (s, 1H), 6.96 (dd, 1H, J=11.3, 1.8), 4.20-4.40 (m, 6H), 4.07 (s, 3H), 3.53 (m, 2H), 2.80 (m, 1H), 1.75-1.90 (m, 4H).

Workup

  1. customthe reaction was quenched with 15 mL of half-saturated NaHCO3
  2. extractionThe material was extracted with 5% MeOH-dcm (3×25 mL)
  3. washwashed with dilute brine (8 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe material was purified through silica gel (35 mL)

Sources & evidence

ORD record
ord-fbf8f3b408c8477fa4b52d9adbe8a220
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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