Diisopropylethylamine → HCID 67515434, compound

HRID 473888Notes

Reaction equation

HRID 473888 reaction equation
Br[C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:12][CH:13]1[CH2:18][CH2:17][N:16]([C:19]([N:21]2[CH2:27][C:26]3[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][C:25]=3[O:24][CH2:23][CH2:22]2)=[O:20])[CH2:15][CH2:14]1.C(=O)(O)[O-].[K+].CCN(C(C)C)C(C)C>CC(N(C)C)=O.O>[CH3:12][CH:13]1[CH2:18][CH2:17][N:16]([C:19]([N:21]2[CH2:27][C:26]3[CH:28]=[C:29]([C:2]4[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[C:5]([NH2:8])=[N:6][CH:7]=4)[CH:30]=[CH:31][C:25]=3[O:24][CH2:23][CH2:22]2)=[O:20])[CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1388782-Amino-5-bromo-3-nitropyridineHCID 516893Potassium BicarbonateHCID 70815174HCID 70815174, compound

Product 1

HCID 67515434HCID 67515434, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
99 °C

Procedure

To a mixture of 5-bromo-3-nitropyridin-2-amine (0.69 g, 3.2 mmol), {4-[(4-methylpiperidin-1-yl)carbonyl]-2,3,4,5-tetrahydro-1,4-benzoxazepine-7-yl}boronic acid (1.0 g, 3.2 mmol) (example 2, step 4), potassium bicarbonate (1.3 g, 2.3 mmol) and DIPEA (1.1 mL, 6.3 mmol) in DMA (12 mL) and water (3 mL) was added dichloro[1,1-bis(diphenylphosphino]ferrocenepalladium (II) dichloromethane adduct (0.12 g, 0.16 mmol). The reaction mixture was stirred at 99° C. for 12 hours and then partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate (2×30 mL) and the combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated. The resulting brown residue was suspended in methanol (20 mL), filtered and washed with ethyl ether (2×30 mL) to afford 5-{4-[(4-methylpiperidin-1-yl)carbonyl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-3-nitropyridin-2-amine (1.0 g, 77% yield) as a yellow solid. MS (EI) for C21H25N5O4: 412 (MH+)

Workup

  1. custompartitioned between ethyl acetate (50 mL) and water (50 mL)
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×30 mL)
  3. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. filtrationfiltered
  7. washwashed with ethyl ether (2×30 mL)

Sources & evidence

ORD record
ord-59d74e296ce04c4885a608556cd4df88
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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