1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 68689712, compound

HRID 1441336Notes

Reaction equation

HRID 1441336 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([C:20]4[N:24]([CH:25]([CH3:27])[CH3:26])[C:23]([CH3:28])=[N:22][CH:21]=4)[C:17]([F:29])=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:3]1.[C:30](O)(=[O:34])[C@H:31]([CH3:33])[OH:32].CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>C(Cl)Cl>[F:29][C:17]1[C:18]([C:20]2[N:24]([CH:25]([CH3:26])[CH3:27])[C:23]([CH3:28])=[N:22][CH:21]=2)=[N:19][C:14]([NH:13][C:10]2[CH:9]=[CH:8][C:7]([N:4]3[CH2:5][CH2:6][C@H:2]([NH:1][C:30](=[O:34])[C@@H:31]([OH:32])[CH3:33])[CH2:3]3)=[CH:12][CH:11]=2)=[N:15][CH:16]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 107689L-Lactic AcidHCID 68687483HCID 68687483, compound

Product 1

HCID 68689712HCID 68689712, compoundYield 30.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N-{4-[(3S)-3-Aminopyrrolidin-1-yl]phenyl}-5-fluoro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidin-2-amine (Example 153; 220 mg, 0.556 mmol), L—lactic acid (61 mg, 0.667 mmol), HOBt mono hydrate (103 mg, 0.667 mmol) and Hunig's base (0.12 ml, 0.667 mmol) in DCM (5 ml) were reacted with EDAC (128 mg, 0.667 mmol) at room temperature under nitrogen for 18 hours. The mixture was diluted with DCM (20 ml) and washed with water (20 ml), 1 N aqueous potassium hydroxide (20 ml) and saturated aqueous sodium chloride (15 ml). The mixture was dried and after evaporation under reduced pressure purified by HPLC on a Phenomenex column, (0-50% acetonitrile/water, 0.2% TFA). The fractions were diluted with water (20 ml), basified with solid potassium carbonate, and extracted twice with EtOAc/DCM (20 ml, 2:1). The solution was washed with saturated aqueous sodium chloride (15 ml), dried and after evaporation under reduced pressure gave the title compound as a yellow solid, (79 mg, 30%). NMR: 1.20 (d, 3H), 1.37 (d, 6H), 1.90-2.04 (m, 1H), 2.11-2.27 (m, 1H), 2.47 (s, 3H), 3.00-3.09 (m, 1H), 3.20-3.47 (m, 3H), 3.91-4.00 (m, 1H), 4.32-4.47 (m, 1H), 5.38 (s, 1H), 5.40-5.49 (m, 1H), 6.49 (d, 2H), 7.30 (s, 1H), 7.32 (d, 2H), 7.76 (d, 1H), 8.40 (d, 1H), 9.06 (s, 1H); m/z 468.

Workup

  1. washwashed with water (20 ml), 1 N aqueous potassium hydroxide (20 ml) and saturated aqueous sodium chloride (15 ml)
  2. customThe mixture was dried
  3. customafter evaporation under reduced pressure
  4. custompurified by HPLC on a Phenomenex column, (0-50% acetonitrile/water, 0.2% TFA)
  5. additionThe fractions were diluted with water (20 ml)
  6. extractionextracted twice with EtOAc/DCM (20 ml, 2:1)
  7. washThe solution was washed with saturated aqueous sodium chloride (15 ml)
  8. customdried
  9. customafter evaporation under reduced pressure

Sources & evidence

ORD record
ord-97521f8ef0d74727aa419d497bd82b36
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

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