Diisopropylamine → HCID 20732840, compound

HRID 352662Notes

Reaction equation

HRID 352662 reaction equation
[C:1]([O:5][C:6](=[O:26])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][N:14]2[C:23](=[O:24])[C:22]3[C:17](=[CH:18][CH:19]=[C:20](I)[CH:21]=3)[N:16]=[CH:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].C(NC(C)C)(C)C.[CH2:34]([N:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1)[C:35]#[CH:36]>CN(C)C=O.CCOC(C)=O.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([O:5][C:6](=[O:26])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][N:14]2[C:23](=[O:24])[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:36]#[C:35][CH2:34][N:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)[CH:21]=3)[N:16]=[CH:15]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 7912DiisopropylamineHCID 4129414-(2-Propyn-1-yl)morpholineHCID 22482157HCID 22482157, compound

Product 1

HCID 20732840HCID 20732840, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 300 mg (0.648 mmol) of 4-(6-iodo-4-oxo-4H-quinazolin-3-ylmethyl)-benzoic acid tert-butyl ester (preparation described above) in 50 mL of dimethylformamide (“DMF”), was added diisopropylamine (4 mol eq.), a catalytic amount of CuI, 4-prop-2-ynyl-morpholine (4 mol eq.), and Pd(PPh3)2Cl2 (a catalytic amount). The reaction mixture was then heated to 50° C. for 15 hours. The reaction was then diluted with 200 mL of EtOAc, and washed with 2×200 mL water, and 1×200 mL brine. The organic layer was dried over MgSO4 and concentrated. The residue was then passed through a silica gel column, elution with 4:1 EtOAc:tetrahydrofuran (“THF”). The product is carried directly to the next step.

Workup

  1. washwashed with 2×200 mL water, and 1×200 mL brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated
  4. washThe residue was then passed through a silica gel column, elution with 4:1 EtOAc

Sources & evidence

ORD record
ord-fd73ef06711441e480b1f65a359fc1e1
Source dataset
uspto-grants-2004_06
Patent number
US06747147B2

Reaction notes

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