Dimethylformamide dimethyl acetal → N'-[(4R)-3'-bromo-7'-(2-fluoro-3-pyridinyl)spiro[5,6-dihydro-1,3-oxazine-4,5'-chromeno[2,3-b]pyridine]-2-yl]-N,N-dimethylmethanimidamide

HRID 455705Notes

Reaction equation

HRID 455705 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C@@:15]3([CH2:20][CH2:19][O:18][C:17]([NH2:21])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:22]4[C:23]([F:28])=[N:24][CH:25]=[CH:26][CH:27]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.CO[CH:31](OC)[N:32]([CH3:34])[CH3:33]>>[Br:1][C:2]1[CH:3]=[C:4]2[C@@:15]3([CH2:20][CH2:19][O:18][C:17](/[N:21]=[CH:31]/[N:32]([CH3:34])[CH3:33])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:22]4[C:23]([F:28])=[N:24][CH:25]=[CH:26][CH:27]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1

Participants

3

Reactant 2

HCID 78373Dimethylformamide dimethyl acetalHCID 58465920(R)-3-bromo-7-(2-fluoropyridin-3-yl)-5',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazin]-2'-amine

Product 1

HCID 87400766N'-[(4R)-3'-bromo-7'-(2-fluoro-3-pyridinyl)spiro[5,6-dihydro-1,3-oxazine-4,5'-chromeno[2,3-b]pyridine]-2-yl]-N,N-dimethylmethanimidamideYield 100%

Conditions

Temperature
100 °C

Procedure

In a 25-mL flask, the (R)-3-bromo-7-(2-fluoropyridin-3-yl)-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-amine (0.350 g, 0.793 mmol) was suspended in 1,1-dimethoxy-N,N-dimethylmethanamine (5.29 mL, 39.7 mmol). The reaction mixture was heated to 100° C. for 1 h. The reaction was concentrated, and the residue was taken up in 5% MeOH/DCM (60 mL) and the organic phase was extracted with dilute brine (2×8 mL), then was dried over sodium sulfate and concentrated. The residue was purified by chromatography (3.5% MeOH/DCM) to afford (R,E)-N′-(3-bromo-7-(2-fluoropyridin-3-yl)-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-yl)-N,N-dimethylformimidamide (394 mg, 0.793 mmol).

Workup

  1. concentrationThe reaction was concentrated
  2. extractionthe organic phase was extracted with dilute brine (2×8 mL)
  3. dry with materialwas dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography (3.5% MeOH/DCM)

Sources & evidence

ORD record
ord-440fe126d79b42d4ad9cf56d26bb7e32
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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