Water → HCID 68690469, compound

HRID 1441324Notes

Reaction equation

HRID 1441324 reaction equation
[N:1]1([C:7]2[CH:29]=[CH:28][C:10]([NH:11][C:12]3[N:17]=[C:16]([C:18]4[N:22]([CH:23]([CH3:25])[CH3:24])[C:21]([CH3:26])=[N:20][CH:19]=4)[C:15]([F:27])=[CH:14][N:13]=3)=[CH:9][C:8]=2[CH3:30])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:31](O)(=[O:35])[C@H:32]([CH3:34])[OH:33].C1C=CC2N(O)N=NC=2C=1.O.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[OH:33][C@@H:32]([CH3:34])[C:31]([N:4]1[CH2:5][CH2:6][N:1]([C:7]2[CH:29]=[CH:28][C:10]([NH:11][C:12]3[N:17]=[C:16]([C:18]4[N:22]([CH:23]([CH3:25])[CH3:24])[C:21]([CH3:26])=[N:20][CH:19]=4)[C:15]([F:27])=[CH:14][N:13]=3)=[CH:9][C:8]=2[CH3:30])[CH2:2][CH2:3]1)=[O:35]

Participants

8

Reactant 6

HCID 962WaterHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 107689L-Lactic AcidHCID 68687096HCID 68687096, compound

Product 1

HCID 68690469HCID 68690469, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-[4-(piperazin-1-yl)3-methylanilino]-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)-5-fluoropyrimidine (Example 122; 490.8 mg, 1.20 mmol), L-lactic acid (129.7 mg, 1.44 mmol), HOBt.H2O (220.5 mg, 1.44 mmol) and DIPEA (0.24 ml, 1.44 mmol) in DMF (5 ml) was cooled to 0° C., followed by addition of EDAC (230.05 mg, 1.44 mmol) in portions. The mixture was then stirred at ambient temperature for 3.5 hours. The solution was concentrated in vacuo, then the residue was partitioned between DCM and water+sat. sodium hydrogen carbonate. The organic extract was washed with water (3 times), brine, dried and concentrated. To a solution of crude product in MeOH (5 ml) was added 1 pellet of KOH and the mixture was stirred at ambient temperature for 20 min. The residue obtained on evaporation was purified by chromatography on silica gel with MeOH:DCM (1:99 to 5:95) to yield the title compound, after trituration with ether, as a solid which was dried in vac oven overnight at 50° C. (415 mg, 72%). NMR: (500 MHz at 373K) 1.27 (d, 3H), 1.40 (d, 6H), 2.28 (s, 3H), 2.48 (s, 3H, under DMSO signal), 2.82 (m, 4H), 3.65 (m, 4H), 4.47 (m, 2H), 5.38 (septet, 1H), 7.00 (d, 1H), 7.35 (m, 2H), 7.40 (dd, 1H), 8.40 (d, 1H), 8.80 (s, 1H); 19F NMR (400 MHz) −149.33 (t, 1F); m/z 482.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. customthe residue was partitioned between DCM and water+
  3. extractionThe organic extract
  4. washwas washed with water (3 times), brine
  5. customdried
  6. concentrationconcentrated
  7. additionTo a solution of crude product in MeOH (5 ml) was added 1 pellet of KOH
  8. stirringthe mixture was stirred at ambient temperature for 20 min
  9. customThe residue obtained on evaporation
  10. customwas purified by chromatography on silica gel with MeOH:DCM (1:99 to 5:95)

Sources & evidence

ORD record
ord-7074e06d99bf452bbab026e69d4bb341
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

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