Methanol → HCID 57756234, compound

HRID 911186Notes

Reaction equation

HRID 911186 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([O:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]4[N:23]=[N:24][C:25]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)=[CH:26][C:27]=4[C:28]([OH:30])=[O:29])=[CH:17][CH:16]=3)=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1.CO.[CH:39]1(N=C=NC2CCCCC2)CCCCC1.CN(C=O)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[C:9]([O:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]4[N:23]=[N:24][C:25]([C:31]5[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=5)=[CH:26][C:27]=4[C:28]([O:30][CH3:39])=[O:29])=[CH:17][CH:16]=3)=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 10868DicyclohexylcarbodiimideHCID 66731501HCID 66731501, compound

Product 1

HCID 57756234HCID 57756234, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A RBF was charged with 4-(dimethylamino)pyridine (5.4 mg, 44 μmol), 3-(4-(3-(2-aminopyrimidin-4-yl)pyridin-2-yloxy)phenylamino)-6-phenylpyridazine-4-carboxylic acid (210 mg, 440 μmol), methanol (53 μl, 1319 μmol) and 1.3 mL DCM. The mixture was cooled to 0° C. and 1,3-dicyclohexylcarbodiimide (100 mg, 484 μmol) dissolved in 1.3 mL DCM was added. The heterogeneous mixture was allowed to warm to RT and stirred for 4 h. 1.3 mL of DMF was added and the reaction was stirred at RT for 72 h. The mixture was filtered through a pad of Celite, washing with DCM. The filtrate was concentrated twice from toluene to remove excess DMF. The crude material was purified by silica gel chromatography, 0-10% MeOH/dDCM. Further purification was done by reverse phase chromatography, Gilson, 5-75% acetonitrile/0.1% TFA over 14 min to provide methyl 3-(4-(3-(2-aminopyrimidin-4-yl)pyridin-2-yloxy)phenylamino)-6-phenylpyridazine-4-carboxylate cleanly as a bright yellow solid. MS m/z=492 [M+H]+. Calc'd for C27H21N7O3: 491.50.

Workup

  1. additionwas added
  2. temperatureto warm to RT
  3. stirringthe reaction was stirred at RT for 72 h
  4. filtrationThe mixture was filtered through a pad of Celite
  5. washwashing with DCM
  6. concentrationThe filtrate was concentrated twice from toluene
  7. customto remove excess DMF
  8. customThe crude material was purified by silica gel chromatography, 0-10% MeOH/dDCM
  9. customFurther purification
  10. waitwas done by reverse phase chromatography, Gilson, 5-75% acetonitrile/0.1% TFA over 14 min

Sources & evidence

ORD record
ord-d8280d1e697f4095a92f790e44b9d003
Source dataset
uspto-grants-2011_09
Patent number
US08022221B2

Reaction notes

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