1-Chloroethyl chloroformate → HCID 67298491, compound

HRID 1520323Notes

Reaction equation

HRID 1520323 reaction equation
[Si]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]=[C:17]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)[N:16]=[C:15]2[NH:28][C:29]1[CH:34]=[CH:33][C:32]([F:35])=[C:31]([Cl:36])[CH:30]=1)(C(C)(C)C)(C)C.ClC(OC(Cl)C)=O>CO>[Cl:36][C:31]1[CH:30]=[C:29]([NH:28][C:15]2[C:14]3[C:19](=[CH:20][CH:21]=[C:12]([CH2:11][CH2:10][CH2:9][OH:8])[CH:13]=3)[N:18]=[C:17]([C:22]3[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=3)[N:16]=2)[CH:34]=[CH:33][C:32]=1[F:35]

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 67298435HCID 67298435, compound

Product 1

HCID 67298491HCID 67298491, compoundYield 91.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 6-(3-(tert-butyldimethylsilyloxy)propyl)-N-(3-chloro-4-fluorophenyl)-2-(pyridin-3-yl)quinazolin-4-amine (0.35 g, 0.67 mmol) in MeOH (10 mL) was added 1-chloroethyl chloroformate (7.2 μl, 0.067 mmol). The mixture was stirred overnight at room temperature. Methanol was removed in vacuo. Sat. NaHCO3 aqueous (10 mL) and CH2Cl2 (10 mL) were added to the residue and stirred for a while. The resultant solid was collected by filtration and dried to give 0.25 g of 3-(4-(3-chloro-4-fluorophenylamino)-2-(pyridin-3-yl)quinazolin-6-yl)propan-1-ol as light yellow solid (91%). MS i/z=409 (M+1) (Method D) (retention time=1.71 min), 1H NMR (300 MHz, DMSO) δ 10.01 (s, 1H), 9.51 (s, 1H), 8.66 (m, 2H), 8.37 (s, 1H), 8.29-8.20 (m, 1H), 7.94-7.67 (m, 3H), 7.63-7.43 (m, 2H), 4.60 (t, J=5.0 Hz, 1H), 3.56-3.35 (m, 2H), 2.94-2.69 (m, 2H), 2.15-1.56 (m, 2H).

Workup

  1. customMethanol was removed in vacuo
  2. additionSat. NaHCO3 aqueous (10 mL) and CH2Cl2 (10 mL) were added to the residue
  3. stirringstirred for a while
  4. filtrationThe resultant solid was collected by filtration
  5. customdried

Sources & evidence

ORD record
ord-a3d867c40d4647e7a79946f9cfafe5cd
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

Loading…