Sodium Hydroxide → HCID 50991219, compound

HRID 1929521Notes

Reaction equation

HRID 1929521 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:10][N:9]=[C:8]([C:11]([OH:13])=O)[CH:7]=1.O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[NH2:33][C:34]1[CH:35]=[CH:36][C:37]([F:48])=[C:38]([C:40]2([CH3:47])[CH2:45][O:44][CH2:43][C:42]([NH2:46])=[N:41]2)[CH:39]=1.[OH-].[Na+]>CO>[NH2:46][C:42]1[CH2:43][O:44][CH2:45][C:40]([C:38]2[CH:39]=[C:34]([NH:33][C:11]([C:8]3[CH:7]=[C:6]([C:2]4[O:1][CH:5]=[CH:4][CH:3]=4)[O:10][N:9]=3)=[O:13])[CH:35]=[CH:36][C:37]=2[F:48])([CH3:47])[N:41]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 10909825-(2-Furyl)isoxazole-3-carboxylic acidHCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrateHCID 58155285HCID 58155285, compound

Product 1

HCID 50991219HCID 50991219, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 5-furan-2-yl-isoxazole-3-carboxylic acid (CAS 98434-06-1) (77.3 mg, 0.42 mmol) in methanol (2 ml) was cooled to 0° C. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMTMM) (135 mg, 0.46 mmol) was added and the mixture stirred at 0° C. for 10 minutes. Thereafter, a solution of (RS)-5-(5-amino-2-fluoro-phenyl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine (85 mg, 0.38 mmol) in methanol (1 ml) was added and the reaction mixture stirred at 0° C. for 2 hours, then kept at 4° C. for 16 hours. For the workup, the reaction mixture was treated at 0° C. with sodium hydroxide (1 N, 6 ml). The yellow suspension was extracted with ethyl acetate (15 ml), then the aqueous layer re-extracted with ethyl acetate (10 ml). The combined organic layers were dried over sodium sulfate and evaporated at reduced pressure. After chromatography on a Silicycle-Si-amine phase using a gradient of dichloromethane and methanol=100/0 to 90/10 the 5-furan-2-yl-isoxazole-3-carboxylic acid [3-((RS)-5-amino-3-methyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-4-fluoro-phenyl]-amide was obtained as a white sold (16 mg, 11% of theory). Mass (calculated) C19H17FN4O4 [384.365]; (found) [M+H]+=385.

Workup

  1. stirringthe reaction mixture stirred at 0° C. for 2 hours
  2. waitkept at 4° C. for 16 hours
  3. extractionThe yellow suspension was extracted with ethyl acetate (15 ml)
  4. extractionthe aqueous layer re-extracted with ethyl acetate (10 ml)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. customevaporated at reduced pressure
  7. customwas obtained as

Sources & evidence

ORD record
ord-b9495b60ca2c4ac2810d94fa30b81f93
Source dataset
uspto-grants-2012_05
Patent number
US08188079B2

Reaction notes

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