Triethylamine → HCID 11547733, compound

HRID 2264585Notes

Reaction equation

HRID 2264585 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[CH2:13]([N:15]1[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[CH:28]=[CH:27][C:25]([NH2:26])=[CH:24][CH:23]=2)[CH2:17][CH2:16]1)[CH3:14].CCN(CC)CC.[Cl:36][C:37]1[N:42]=[CH:41][N:40]=[C:39]([O:43][C:44]2[CH:45]=[C:46]3[C:50](=[CH:51][CH:52]=2)[NH:49][CH2:48][CH2:47]3)[CH:38]=1>C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+].O.CCOC(C)=O>[CH2:13]([N:15]1[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([NH:26][C:2]([N:49]3[C:50]4[C:46](=[CH:45][C:44]([O:43][C:39]5[CH:38]=[C:37]([Cl:36])[N:42]=[CH:41][N:40]=5)=[CH:52][CH:51]=4)[CH2:47][CH2:48]3)=[O:4])=[CH:27][CH:28]=2)[CH2:17][CH2:16]1)[CH3:14]

Participants

9

Reactant 4

HCID 8471Triethylamine2×HCID 94429TriphosgeneHCID 10849964-[(4-Ethylpiperazin-1-yl)methyl]anilineHCID 858916285-(6-Chloro-pyrimidin-4-yloxy)-2,3-dihydro-indole

Product 1

HCID 11547733HCID 11547733, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Procedure

104 mg (0.35 mMol) triphosgene are dissolved in 13 ml ice-cooled CH2Cl2. Then a solution of 230 mg (1.05 mMol) 4-(4-ethylpiperazin-1-ylmethyl)-aniline and 209 μl (1.50 mMol) Et3N in 6 ml CH2Cl2 is added during 8 min. After 3 additional minutes, the mixture is warmed up to rt by a water bath and then a solution of 1.0 mMol 5-(6-chloro-pyrimidin-4-yloxy)-2,3-dihydro-1H-indole (Step 14.1) and 139 μl (1.00 mMol) Et3N in 6 ml CH2Cl2 is added during 8 min. After 2 h at rt, the mixture is diluted with sat. Na2CO3 solution/water 1:1 and EtOAc, the aqueous phase separated off and extracted twice with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Crystallization from DIPE gives the title compound: MS: [M+1]+=493/495; TLC(CH2Cl2/MeOH/NH3conc. 90:10:1): Rf=0.24; HPLC: AtRet=10.5.

Workup

  1. customthe aqueous phase separated off
  2. extractionextracted twice with EtOAc
  3. washThe organic layers are washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customCrystallization from DIPE

Sources & evidence

ORD record
ord-e0d9f1ccb0ff467b8c8c1212df34eb08
Source dataset
uspto-grants-2010_12
Patent number
US07855215B2

Reaction notes

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