1,2-Dichloroethane → HCID 71254774, compound

HRID 1507647Notes

Reaction equation

HRID 1507647 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:16]([F:19])([F:18])[F:17])[O:11][C:12]=2[C:13]([OH:15])=O)=[CH:4][CH:3]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH2:43][C:44]1[CH:45]=[CH:46][C:47]([CH3:63])=[C:48]([NH:50][C:51]2[CH:52]=[C:53]3[C:58](=[CH:59][CH:60]=2)[N:57]=[CH:56][N:55]([CH3:61])[C:54]3=[O:62])[CH:49]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([C:16]([F:19])([F:18])[F:17])[O:11][C:12]=2[C:13]([NH:43][C:44]2[CH:45]=[CH:46][C:47]([CH3:63])=[C:48]([NH:50][C:51]3[CH:52]=[C:53]4[C:58](=[CH:59][CH:60]=3)[N:57]=[CH:56][N:55]([CH3:61])[C:54]4=[O:62])[CH:49]=2)=[O:15])=[CH:6][CH:7]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 689395096-[(5-Amino-2-methylphenyl)amino]-3-methyl-4(3H)-quinazolinoneHCID 71254927HCID 71254927, compound

Product 1

HCID 71254774HCID 71254774, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a flask containing DCM (3 mL) on ice was added 4-(4-fluorophenyl)-2-(trifluoromethyl)oxazole-5-carboxylic acid (S-41) (76 mg, 0.28 mmol), EDC (47.2 mg, 0.3 mmol), HOAt (48.9 mg, 0.36 mmol), and DIPEA (0.193 mL, 1.10 mmol). The resulting solution was stirred for 1 hr followed by the addition of 6-((5-amino-2-methylphenyl)amino)-3-methylquinazolin-4(3H)-one (HGM-7) (77.4 mg, 0.28 mmol). The reaction was stirred for 18 hours at ambient temperature at which point the solution was made basic by the addition of saturated sodium bicarbonate (10 mL) which was then extracted with DCM (2×10 mL) and EtOAc (2×10 mL). The organic extracts were washed with brine, combined, dried over Na2SO4, and concentrated. The crude material was fractionated by SiO2 chromatography (stepwise gradient of DCM to 90% DCM/10% MeOH, desired product elutes in 5% MeOH)(101 mg, 67% yield). 1HNMR (400 MHz, CDCl3): d 8.9 (s, 1H), 7.82 (m, 2H), 7.80 (s, 1H), 7.55 (d, 1H, J=2.4 Hz), 7.50 (s, 1H), 7.41 (d, 1H, J=8.4 hz), 7.27 (m, 2H), 7.03 (d, 1H, J=8.4 Hz), 6.95 (t, 2H, J=8.8 Hz), 3.44 (s, 3H), 2.12 (s, 3H).

Workup

  1. stirringThe reaction was stirred for 18 hours at ambient temperature at which point the solution
  2. extractionwas then extracted with DCM (2×10 mL) and EtOAc (2×10 mL)
  3. washThe organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-0830731fb5e34e699a44a9c32ee751c8
Source dataset
uspto-grants-2015_12
Patent number
US09221805B2

Reaction notes

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