tert-butyl N-(3-bromopropyl)carbamate → (3-{4-[3-Chloro-4-(pyridin-2-ylmethoxy)-phenylamino]-7-methoxy-quinazolin-6-yloxy}-propyl)-carbamic acid tert-butyl ester

HRID 415020Notes

Reaction equation

HRID 415020 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:28][CH3:29])=[C:24]([OH:27])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[C:30]([O:34][C:35](=[O:41])[NH:36][CH2:37][CH2:38][CH2:39]Br)([CH3:33])([CH3:32])[CH3:31]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[C:30]([O:34][C:35](=[O:41])[NH:36][CH2:37][CH2:38][CH2:39][O:27][C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][C:23]=1[O:28][CH3:29])[N:20]=[CH:19][N:18]=[C:17]2[NH:16][C:4]1[CH:5]=[CH:6][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)=[C:2]([Cl:1])[CH:3]=1)([CH3:33])([CH3:32])[CH3:31]

Participants

5

Reactant 2

HCID 4460490tert-butyl N-(3-bromopropyl)carbamateHCID 66623412HCID 66623412, compound

Product 1

HCID 66623588(3-{4-[3-Chloro-4-(pyridin-2-ylmethoxy)-phenylamino]-7-methoxy-quinazolin-6-yloxy}-propyl)-carbamic acid tert-butyl esterYield 73.7%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

CsOH monohydrate (0.452 g, 2.69 mmol) was added to a mixture of 4-[3-Chloro-4-(pyridin-2-ylmethoxy)-phenylamino]-7-methoxy-quinazolin-6-ol (1 g, 2.45 mmol), (3-bromo-propyl)-carbamic acid tert-butyl ester (0.64 g, 2.69 mmol), tetrabutylammonium iodide (5 mg) and 4 Å molecular sieves (2 g) in DMF (10 mL) at room temp. Stir for 3 hours. The reaction mixture was then filtered through celite and washed with EtOAc (30 mL). The organic solution was washed with water (20 mL) and concentrated. FLC (10:1 EtOAc:Hexanes) provided desired product (1.02 g, 73.7%).

Workup

  1. filtrationThe reaction mixture was then filtered through celite
  2. washwashed with EtOAc (30 mL)
  3. washThe organic solution was washed with water (20 mL)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-d2b85822fc80492fa13f9c88b9bc7696
Source dataset
uspto-grants-2012_01
Patent number
US08088766B2

Reaction notes

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