Trifluoroacetic acid → 3-[(2-Amino-6-{[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]amino}-pyrimidin-4-yl)amino]propan-1-ol

HRID 16457

Reaction equation

HRID 16457 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH2:8])[N:5]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]4[NH:23][CH:24]=[CH:25][C:18]=34)=[C:12]([F:26])[CH:11]=2)[CH:3]=1.C[O:28][C:29]1C=C(OC)C=C[C:30]=1[CH2:31][NH:32]CCCO.C(O)(C(F)(F)F)=O.C(OCC)(=O)C>C(O)CCC.C(N(C(C)C)C(C)C)C.C(Cl)Cl>[NH2:8][C:6]1[N:7]=[C:2]([NH:32][CH2:31][CH2:30][CH2:29][OH:28])[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]4[NH:23][CH:24]=[CH:25][C:18]=34)=[C:12]([F:26])[CH:11]=2)[N:5]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 109661863-[(2,4-Dimethoxybenzyl)amino]propan-1-olHCID 587332416-Chloro-N4-[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]pyrimidine-2,4-diamine

Product 1

HCID 179792883-[(2-Amino-6-{[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]amino}-pyrimidin-4-yl)amino]propan-1-ol

Reagents, catalysts & solvents 3

HCID 2631-ButanolSolventHCID 6344DichloromethaneSolventHCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
130 °C

Procedure

78 mg (0.21 mmol) of 6-chloro-N4-[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)-phenyl]pyrimidine-2,4-diamine (from example 60), 190 mg (0.84 mmol) of 3-[(2,4-dimethoxybenzyl)amino]propan-1-ol in 1 ml of 1-butanol and 0.37 ml of N-ethyl-diisopropylamine are, in a closed pressure vessel, heated at 130° C. overnight. Volatile components are removed under reduced pressure, and the residue is purified by preparative HPLC. The substrate obtained is taken up in 2 ml of DCM, and 0.5 ml of TFA is added. The mixture is stirred at RT for 20 min and then poured into ethyl acetate and extracted with sat. sodium carbonate solution. The organic phase is dried over sodium sulfate and the solvent is removed under reduced pressure. The residue is purified by preparative HPLC.

Workup

  1. customVolatile components are removed under reduced pressure
  2. customthe residue is purified by preparative HPLC
  3. customThe substrate obtained
  4. extractionextracted with sat. sodium carbonate solution
  5. dry with materialThe organic phase is dried over sodium sulfate
  6. customthe solvent is removed under reduced pressure
  7. customThe residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-d15089b0ff284eaf876b69e07ef3cd4b
Source dataset
uspto-grants-2010_06
Patent number
US07737153B2

Linked notes

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