1,4-Dioxane → (S)-3-(6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-7-(5-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-c]pyridine-5,4'-oxazol]-2'-amine

HRID 335926Notes

Reaction equation

HRID 335926 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[O:8][C:9]3[C:14]([C@@:15]4([CH2:19][O:18][C:17]([NH2:20])=[N:16]4)[C:4]=2[CH:3]=1)=[CH:13][C:12]([C:21]1[CH:22]=[N:23][CH:24]=[C:25]([F:27])[CH:26]=1)=[CH:11][CH:10]=3.[CH3:28][C:29]1([CH3:44])[O:34][CH2:33][CH2:32][C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30]1.O1CCOCC1>CCOC(C)=O.O>[CH3:28][C:29]1([CH3:44])[O:34][CH2:33][CH2:32][C:31]([C:2]2[N:7]=[CH:6][C:5]3[O:8][C:9]4[C:14]([C@@:15]5([CH2:19][O:18][C:17]([NH2:20])=[N:16]5)[C:4]=3[CH:3]=2)=[CH:13][C:12]([C:21]2[CH:22]=[N:23][CH:24]=[C:25]([F:27])[CH:26]=2)=[CH:11][CH:10]=4)=[CH:30]1

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 585467722-(6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86658490(S)-3-chloro-7-(5-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-c]pyridine-5,4'-oxazol]-2'-amine

Product 1

HCID 53464570(S)-3-(6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-7-(5-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-c]pyridine-5,4'-oxazol]-2'-amine

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A glass microwave reaction vessel was charged with (S)-3-chloro-7-(5-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazol]-2′-amine (0.250 g, 0.653 mmol; prepared as described in Method BB41), 2-(6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.311 g, 1.306 mmol), bis(di-tert-butylphenylphosphine)dichloropalladium (II) (0.041 g, 0.065 mmol), dioxane (3 mL) and water (0.8 mL). The reaction mixture was exposed to MW radiation at 105° C. for 30 min in a microwave reactor. The mixture was diluted with EtOAc and water. The organic layer was washed with saturated sodium carbonate and dried over sodium sulfate. The crude material was initially purified by silica gel chromatography using 2-10% MeOH (2M NH3)-CH2Cl2) followed by further purification by SFC chromatography to give (S)-3-(6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-7-(5-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazol]-2′-amine

Workup

  1. customA glass microwave reaction vessel
  2. washThe organic layer was washed with saturated sodium carbonate
  3. dry with materialdried over sodium sulfate
  4. customThe crude material was initially purified by silica gel chromatography
  5. customfollowed by further purification by SFC chromatography

Sources & evidence

ORD record
ord-0f72b9cbaaa14bceb5fb12eceaf0ef94
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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