Acetonitrile → HCID 60202338, compound

HRID 515852Notes

Reaction equation

HRID 515852 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([CH:12]([NH2:14])[CH3:13])[C:9]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[N:7]2.[NH2:22][C:23]1[C:28]([C:29]#[N:30])=[C:27](Cl)[N:26]=[CH:25][N:24]=1.C(N(CC)C(C)C)(C)C.C(#N)C>C(O)CCC>[NH2:22][C:23]1[C:28]([C:29]#[N:30])=[C:27]([NH:14][CH:12]([C:10]2[C:9]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=3)=[C:8]3[C:3]([CH:4]=[CH:5][N:6]=[N:7]3)=[C:2]([Cl:1])[CH:11]=2)[CH3:13])[N:26]=[CH:25][N:24]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 58368472HCID 58368472, compound

Product 1

HCID 60202338HCID 60202338, compoundYield 45.8%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of the single enantiomer of 1-[5-chloro-8-(3-fluorophenyl)cinnolin-7-yl]ethanamine (400 mg, 1.3 mmol) from step O, 4-amino-6-chloropyrimidine-5-carbonitrile (250 mg, 1.6 mmol), and N,N-diisopropylethylamine (0.69 mL, 4 mmol) in 1-butanol (13 mL) was heated at 120° C. for 3 hours. The reaction mixture was concentrated and the residue was purified by RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 60 mL/min). The pure fractions were concentrated to remove all of the acetonitrile and the remaining aqueous solution was saturated with sodium bicarbonate. The aqueous solution was extracted with ethyl acetate (300 mL). The organic layer was separated, washed with brine, dried with sodium sulfate, filtered, and concentrated to give a solid. This solid was treated with acetonitrile and concentrated (2×) to give the desired product (0.25 g, 44%). LCMS for C21H16ClFN7 (M+H)+: m/z=420.1; Found: 420.1. 1H NMR (300 MHz, DMSO-d6): δ 9.48 (d, J=6.0 Hz, 1 H), 8.44 (d, J=7.8 Hz, 1 H), 8.28 (d, J=6.0 Hz, 1 H), 7.87 - 7.81 (m, 2 H), 7.61 - 7.44 (m, 2 H), 7.34 - 7.17 (m, 4 H), 5.24-5.11 (m, 1 H), 1.43 (d, J=7.0 Hz, 3 H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was purified by RP-HPLC (XBridge C18 column
  3. washeluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 60 mL/min)
  4. concentrationThe pure fractions were concentrated
  5. customto remove all of the acetonitrile
  6. extractionThe aqueous solution was extracted with ethyl acetate (300 mL)
  7. customThe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried with sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto give a solid
  13. concentrationconcentrated (2×)

Sources & evidence

ORD record
ord-7737fc54f28f469c90a8b632d4688dae
Source dataset
uspto-grants-2015_08
Patent number
US09108984B2

Reaction notes

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