Hydrochloric Acid → HCID 58465961, compound

HRID 455684Notes

Reaction equation

HRID 455684 reaction equation
C[Al](C)C.C1(C)C=CC=CC=1.[NH2:12][C:13]1([CH2:29][O:30][CH:31]([CH:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)[C:32]#[N:33])[C:26]2[CH:25]=[C:24]([Cl:27])[N:23]=[CH:22][C:21]=2[O:20][C:19]2[C:14]1=[CH:15][C:16]([Br:28])=[CH:17][CH:18]=2.Cl>ClCCCl.C(Cl)Cl>[Br:28][C:16]1[CH:15]=[C:14]2[C:13]3([N:12]=[C:32]([NH2:33])[CH:31]([CH:34]4[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]4)[O:30][CH2:29]3)[C:26]3[CH:25]=[C:24]([Cl:27])[N:23]=[CH:22][C:21]=3[O:20][C:19]2=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 16682925TrimethylaluminumHCID 86658386HCID 86658386, compound

Product 1

HCID 58465961HCID 58465961, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Trimethylaluminum, as a 2 M solution in toluene, (0.973 ml, 1.947 mmol) was added dropwise via syringe to a solution of 2-((5-amino-7-bromo-3-chloro-5H-chromeno[2,3-c]pyridin-5-yl)methoxy)-2-cyclohexylacetonitrile (0.563 g, 1.217 mmol) in DCE (12 ml) at RT. After stirring 14 hours, the reaction was cooled to 0° C. and 1 N aq. HCl (12 ml, 12 mmol) was added dropwise via syringe (slowly at first until vigorous reaction subsided) and the mixture was stirred at 0° C. for 10 minutes and then at RT before being diluted with DCM. The layers were separated and the aqueous layer was extracted with DCM. The combined organic extracts were washed with 1 N aq. NaOH, saturated aqueous sodium chloride, and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to give the crude material. The crude material was purified by silica gel chromatography by eluting with 1:20 MeOH in DCM, to provide 7-bromo-3-chloro-6′-cyclohexyl-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine as a mixture of racemic diastereomers. [M+H]=462.0.

Workup

  1. customfirst until vigorous reaction
  2. stirringwas stirred at 0° C. for 10 minutes
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with DCM
  5. washThe combined organic extracts were washed with 1 N aq. NaOH, saturated aqueous sodium chloride
  6. dry with materialdried over sodium sulfate
  7. filtrationThe solution was filtered
  8. concentrationconcentrated in vacuo
  9. customto give the crude material
  10. customThe crude material was purified by silica gel chromatography
  11. washby eluting with 1:20 MeOH in DCM

Sources & evidence

ORD record
ord-c7593c49ef8b4002986440e6cdf59be5
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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