Dimethylamine → 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N,N-dimethylacetamide

HRID 1808444Notes

Reaction equation

HRID 1808444 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]([OH:28])=O)[N:12]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.C[CH2:33][N:34](C(C)C)[CH:35](C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CNC>C(Cl)Cl.CN(C=O)C>[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]([N:34]([CH3:35])[CH3:33])=[O:28])[N:12]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

7

Reactant 4

HCID 674DimethylamineHCID 81531Diisopropylethylamine2×HCID 2724699PyBOP2×HCID 593619882-(3-(4-((1H-indazol-5-yl)amino)quinazolin-2-yl)phenoxy)acetic acid

Product 1

HCID 593619122-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N,N-dimethylacetamideYield 37%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)acetic acid (80 mg, 0.16 mmol) in dry CH2Cl2:DMF (2.0:0.1 mL), added DIEA (29 μL, 0.16 mmol) and PyBOP® (46 mg, 0.088 mmol). After stirring the mixture at RT for 15 minutes, dimethylamine was bubbled through the solution for 15 minutes. Added another 1.0 equivalent of DIEA and 0.55 equivalents of PyBOP® after stirring the solution for 15 minutes, followed by dimethylamine bubbling for an additional 15 minutes. The solvent was removed in vacuo and the crude material was purified by prep HPLC (method 20-45—90 mins) to afford 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N,N-dimethylacetamide (26 mg, 0.059 mmol, 37%).

Workup

  1. customdimethylamine was bubbled through the solution for 15 minutes
  2. stirringafter stirring the solution for 15 minutes
  3. customThe solvent was removed in vacuo
  4. customthe crude material was purified by prep HPLC (method 20-45—90 mins)

Sources & evidence

ORD record
ord-3ec364c371334d4682aefee39829f5ad
Source dataset
uspto-grants-2013_01
Patent number
US08357693B2

Reaction notes

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