Pyridine → HCID 68277905, compound

HRID 1423267Notes

Reaction equation

HRID 1423267 reaction equation
Cl.[NH2:2][OH:3].N1C=CC=CC=1.[CH:10]1([C:13]2[CH:17]=[C:16]([C:18]3[CH:27]=[C:26]4[C:21]([C:22](=[O:46])[N:23]([C:39]5[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=5)[C:24]([CH2:28][CH2:29][CH2:30][CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[N:25]4)=[CH:20][CH:19]=3)ON=2)[CH2:12][CH2:11]1>>[CH:10]1([C:13]2[O:3][N:2]=[C:16]([C:18]3[CH:27]=[C:26]4[C:21]([C:22](=[O:46])[N:23]([C:39]5[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=5)[C:24]([CH2:28][CH2:29][CH2:30][CH2:31][C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])=[N:25]4)=[CH:20][CH:19]=3)[CH:17]=2)[CH2:12][CH2:11]1

Participants

4

Reactant 3

HCID 1049PyridineHCID 443297Hydroxyamine hydrochlorideHCID 68278519HCID 68278519, compound

Product 1

HCID 68277905HCID 68277905, compoundYield 63%

Conditions

Temperature
110 °C

Procedure

A solution of 8A (27 mg, 0.053 mmol) and hydroxylamine hydrochloride (4.3 mg, 0.062 mmol) in pyridine (1 mL, 10 mmol) was stirred at 60° C. for 7 h. The reaction was then stirred at at 110° C. for 16 h. The reaction was quenched with 0.1N HCl and diluted with DCM. The organic layer was removed and the aqueous phase was extracted with DCM (3×). The combined organics were concentrated. The residue was purified by flash chromatography (0% to 20% (12 min) to 70% (10 min) EtOAc/hexanes) to yield an inseparable mixture of tert-butyl 5-(7-(3-cyclopropylisoxazol-5-yl)-3-(4-fluorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)pentanoate and regioisomer tert-butyl 5-(7-(5-cyclopropylisoxazol-3-yl)-3-(4-fluorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)pentanoate (17 mg; Yield=63%), MS (M+H)=504.3.

Workup

  1. customThe reaction was quenched with 0.1N HCl
  2. additiondiluted with DCM
  3. customThe organic layer was removed
  4. extractionthe aqueous phase was extracted with DCM (3×)
  5. concentrationThe combined organics were concentrated
  6. customThe residue was purified by flash chromatography (0% to 20% (12 min) to 70% (10 min) EtOAc/hexanes)
  7. customto yield

Sources & evidence

ORD record
ord-f67c3919c5e644a297e6eca2cb8ad11c
Source dataset
uspto-grants-2015_01
Patent number
US08927559B2

Reaction notes

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