1,2-Dichloroethane → HCID 118126849, compound

HRID 1482884Notes

Reaction equation

HRID 1482884 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[CH:20]=[N:21][C:22]([NH:25][C:26]3([C:29](O)=[O:30])[CH2:28][CH2:27]3)=[N:23][CH:24]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.[Cl-].[NH4+].C(Cl)CCl.C1C=CC2N(O)N=[N:44]C=2C=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C=O)C>[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[CH:24]=[N:23][C:22]([NH:25][C:26]3([C:29]([NH2:44])=[O:30])[CH2:28][CH2:27]3)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:16])[F:17])[CH:12]=[CH:11][N:10]=2)[CH:7]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 72709532HCID 72709532, compound

Product 1

HCID 118126849HCID 118126849, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}cyclopropanecarboxylic acid (177 mg, 0.411 mmol, as prepared in Example 2.3), ammonium chloride (66 mg, 1.2 mmol), EDC (0.158 g, 0.823 mmol), HOBT (0.111 g, 0.823 mmol), N,N-diisopropylethylamine (0.359 mL, 2.06 mmol) and DMF (4 mL) were combined and stirred at rt for 14 hours. The reaction mixture was concentrated in vacuo, then diluted with water and extracted with EtOAc (2×). The combined organic portions were washed with saturated sodium bicarbonate, then brine. The organic portions were collected and dried with MgSO4, filtered, and concentrated in vacuo to afford a brown solid. The residue was diluted with 1:1 CH2Cl2:hexanes and stirred for 10 min, then filtered. The solid was washed with 1:1 CH2Cl2:hexanes, then methanol to afford 1-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyrimidin-2-yl]amino}cyclopropanecarboxamide. MS ESI calcd. for C20H19F3N2O [M+H]+ 430. found 430. 1H NMR (500 MHz, DMSO-d) δ 10.22 (s, 1H), 8.82 (d, J=4.8 Hz, 1H), 8.60-8.55 (m, 2H), 7.85 (s, 1H), 7.82 (s, 1H), 7.47 (s, 1H), 7.26 (d, J=4.9 Hz, 1H), 7.17 (s, 1H), 7.11 (s, 1H), 6.92 (s, 1H), 2.32 (s, 3H), 1.33 (d, J=3.3 Hz, 2H), 0.92 (d, J=3.2 Hz, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with water
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic portions were washed with saturated sodium bicarbonate
  5. customThe organic portions were collected
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a brown solid
  10. filtrationfiltered
  11. washThe solid was washed with 1:1 CH2Cl2

Sources & evidence

ORD record
ord-7f226a2f0a8849168b9c614efbd67880
Source dataset
uspto-grants-2016_08
Patent number
US09416111B2

Reaction notes

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