Cyclopropanecarbonyl chloride → HCID 89488375, compound

HRID 570137Notes

Reaction equation

HRID 570137 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[CH:18]=3)=[C:11]3[O:12][CH2:13][CH2:14][CH2:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[CH:33]1([C:36](Cl)=[O:37])[CH2:35][CH2:34]1>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:36]([CH:33]4[CH2:35][CH2:34]4)=[O:37])[CH:18]=3)=[C:11]3[O:12][CH2:13][CH2:14][CH2:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 89488359HCID 89488359, compound

Product 1

HCID 89488375HCID 89488375, compoundYield 33.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

93 mg (0.3 mmol) of 4-[2-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl]pyridin-2-amine and 46 mg (0.36 mmol, 1.2 eq) of Huenigs base are dissolved in 2 mL tetrahydrofuran. To this are added 63 mg of cyclopropanecarbonyl chloride (0.6 mmol, 2 eq) and the reaction mixture is stirred for 16 hrs at room temperature. Next, the volatile components are removed under vacuum and the crude material treated with 3 mL NH3 in methanol (7 molar). The mixture is stirred for 16 hrs at room temperature and then evaporated. The crude product is purified by preparative HPLC (Phenomenex AMA Gemini C18; 110 A; 10 μm 100×30 mm, gradient: 0-2.0 mins 80% water, 20% acetonitrile, 2.0-12.0 mins linear gradient up to 25% water, 75% acetonitrile, 12.0-16.0 mins 5% water, 95% acetonitrile, modifier 15% NH4OH in H2O, addition of the modifier at 1.0 mL/min throughout the separation). 38.2 mg (33%) of N-{4-[2-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl]pyridin-2-yl}cyclo-propanecarboxamide are obtained as a colourless solid.

Workup

  1. customNext, the volatile components are removed under vacuum
  2. additionthe crude material treated with 3 mL NH3 in methanol (7 molar)
  3. stirringThe mixture is stirred for 16 hrs at room temperature
  4. customevaporated
  5. customThe crude product is purified by preparative HPLC (Phenomenex AMA Gemini C18
  6. addition10 μm 100×30 mm, gradient: 0-2.0 mins 80% water, 20% acetonitrile, 2.0-12.0 mins linear gradient up to 25% water, 75% acetonitrile, 12.0-16.0 mins 5% water, 95% acetonitrile, modifier 15% NH4OH in H2O, addition of the modifier at 1.0 mL/min throughout the separation)

Sources & evidence

ORD record
ord-bae43e82ce064d6c8eae769dbcaa274a
Source dataset
uspto-grants-2015_05
Patent number
US09023844B2

Reaction notes

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