N-Methylisopropylamine → 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-isopropyl-N-methylacetamide

HRID 1406920Notes

Reaction equation

HRID 1406920 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=[C:13]([C:21]4[CH:22]=[C:23]([CH:29]=[CH:30][CH:31]=4)[O:24][CH2:25][C:26](O)=[O:27])[N:12]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C[CH2:66][N:67](C(C)C)[CH:68]([CH3:70])[CH3:69].CNC(C)C>C(Cl)Cl>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]3[C:16]4[C:15](=[CH:20][CH:19]=[CH:18][CH:17]=4)[N:14]=[C:13]([C:21]4[CH:22]=[C:23]([CH:29]=[CH:30][CH:31]=4)[O:24][CH2:25][C:26]([N:67]([CH:68]([CH3:70])[CH3:69])[CH3:66])=[O:27])[N:12]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

6

Reactant 4

HCID 78485N-MethylisopropylamineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 593619882-(3-(4-((1H-indazol-5-yl)amino)quinazolin-2-yl)phenoxy)acetic acid

Product 1

HCID 593618372-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-isopropyl-N-methylacetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)acetic acid (120 mg, 0.29 mmol), PyBOP® (150 mg, 0.29 mmol), DIEA (152 μL, 0.87 mmol) in CH2Cl2 (5 mL) was stirred at RT for 10-15 minutes. To this solution of activated acid was added N-methylpropan-2-amine (30 μL, 0.29 mmol). The reaction mixture was stirred at RT for 3 h and concentrated in vacuo. The crude product was purified using prep HPLC (method 5-25-50—80 mins) and was further washed with ethyl ether and drops of CH2Cl2 to afford 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-isopropyl-N-methylacetamide. (12 mg, 0.025 mmol, 9%)

Workup

  1. stirringThe reaction mixture was stirred at RT for 3 h
  2. concentrationconcentrated in vacuo
  3. customThe crude product was purified
  4. washwas further washed with ethyl ether and drops of CH2Cl2

Sources & evidence

ORD record
ord-657180c270e94752b9867d2f10f4507d
Source dataset
uspto-grants-2014_12
Patent number
US08916576B2

Reaction notes

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