4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → HCID 71542703, compound

HRID 931638Notes

Reaction equation

HRID 931638 reaction equation
[O:1]1[CH2:6][CH2:5][C@:4]2([C:19]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[O:13][C:12]3[C:7]2=[CH:8][C:9]([NH2:20])=[CH:10][CH:11]=3)[N:3]=[C:2]1[NH2:21].[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([C:29](O)=[O:30])=[N:27][CH:28]=1.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CO.CCOC(C)=O>[NH2:21][C:2]1[O:1][CH2:6][CH2:5][C@:4]2([C:19]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[O:13][C:12]3[C:7]2=[CH:8][C:9]([NH:20][C:29](=[O:30])[C:26]2[CH:25]=[CH:24][C:23]([Cl:22])=[CH:28][N:27]=2)=[CH:10][CH:11]=3)[N:3]=1

Participants

6

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride2×HCID 27628725-Chloro-2-picolinic acid2×HCID 117600717HCID 117600717, compound

Product 1

HCID 71542703HCID 71542703, compoundYield 29.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

The (S)-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazine]-2′,7-diamine (0.008 g, 0.028 mmol) was dissolved in MeOH (1 mL). The 5-chloropicolinic acid (4.91 mg, 0.031 mmol) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride (8.63 mg, 0.031 mmol) were added. After 2 h, additional MeOH (0.5 mL) was added, followed by additional 5-chloropicolinic acid (2.5 mg, 0.015 mmol) and additional 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride (4.3 mg, 0.015 mmol). After 14 h, the reaction was taken up in EtOAc (75 mL). The organic phase was washed with half-saturated NaHCO3 (2×10 mL), then with saturated brine (10 mL), dried over MgSO4 and concentrated. The residue was purified by preparative TLC, using 12.5% MeOH-dcm to afford (S)—N-(2′-amino-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-7-yl)-5-chloropicolinamide (3.5 mg, 0.0083 mmol). MS (m/z) 422 (M+H)+. 1H NMR (400 MHz, CDCl3) δ: 9.88 (s, 1H), 8.57 (s, 1H), 8.27 (m, 2H), 7.89 (d, 1H, J=8.4 Hz), 7.82 (d, 1H, J=7.4 Hz), 7.76 (m, 2H), 7.32 (d, 1H, J=8.4 Hz), 7.20 (m, 1H), 4.23 (m, 1H), 4.11 (m, 1H), 1.98 (m, 1H), 1.93 (m, 1H).

Workup

  1. waitAfter 14 h
  2. washThe organic phase was washed with half-saturated NaHCO3 (2×10 mL)
  3. dry with materialwith saturated brine (10 mL), dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-ec650e5e429d41f0ac12aea5de016527
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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