Isopropylamine → 2-(3-(4-(1H-Indazol-5-ylamino)-2-quinazolinyl)phenoxy)-N-(1-methylethyl)acetamide

HRID 1808460Notes

Reaction equation

HRID 1808460 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+](O[N:49]2N=N[C:51]3C=CC=[CH:55][C:50]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CC(N)C>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]([NH:49][CH:50]([CH3:55])[CH3:51])=[O:27])[N:12]=3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

7

Reactant 4

HCID 6363Isopropylamine2×HCID 81531Diisopropylethylamine2×HCID 2724699PyBOP2×HCID 593619882-(3-(4-((1H-indazol-5-yl)amino)quinazolin-2-yl)phenoxy)acetic acid

Product 1

HCID 119501702-(3-(4-(1H-Indazol-5-ylamino)-2-quinazolinyl)phenoxy)-N-(1-methylethyl)acetamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)acetic acid (70 mg, 0.14 mmol), PyBOP® (40 mg, 0.077 mmol), DIEA (24 μL, 0.14 mmol) in dry CH2Cl2:DMF (2:0.1 mL) was stirred at RT for 15 minutes. To this solution of activated acid was added propan-2-amine (5.4 mg, 0.091 mmol). After 30 minutes, 1.0 equivalent of DIEA and 0.55 equivalents of PyBOP® were added. After stirring the solution for 15 minutes, 0.65 equivalents of propan-2-amine were added and the mixture was stirred for an additional 30 minutes. The solvent was removed in vacuo and the crude product was purified using prep HPLC (25-50—90 mins) to afford 2-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-isopropylacetamide. (40 mg, 0.086 mmol, 61%).

Workup

  1. stirringthe mixture was stirred for an additional 30 minutes
  2. customThe solvent was removed in vacuo
  3. customthe crude product was purified

Sources & evidence

ORD record
ord-4a0d13ec97cd4a4987665d24833ef72a
Source dataset
uspto-grants-2013_01
Patent number
US08357693B2

Reaction notes

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