Water → 6-(6-Amino-pyrimidin-4-yloxy)-3,4-dihydro-2H-quinoline-1-carboxylic acid (4-pyrrolidin-1-ylmethyl-3-trifluoromethyl-phenyl)-amide

HRID 2264602Notes

Reaction equation

HRID 2264602 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[NH:15][CH2:14][CH2:13][CH2:12]3)[CH:3]=1.C1([O:25][C:26](=O)[NH:27][C:28]2[CH:33]=[CH:32][C:31]([CH2:34][N:35]3[CH2:39][CH2:38][CH2:37][CH2:36]3)=[C:30]([C:40]([F:43])([F:42])[F:41])[CH:29]=2)C=CC=CC=1.C(N(C(C)C)CC)(C)C.O>CS(C)=O.CCOC(C)=O>[N:35]1([CH2:34][C:31]2[CH:32]=[CH:33][C:28]([NH:27][C:26]([N:15]3[C:16]4[C:11](=[CH:10][C:9]([O:8][C:4]5[CH:3]=[C:2]([NH2:1])[N:7]=[CH:6][N:5]=5)=[CH:18][CH:17]=4)[CH2:12][CH2:13][CH2:14]3)=[O:25])=[CH:29][C:30]=2[C:40]([F:41])([F:42])[F:43])[CH2:39][CH2:38][CH2:37][CH2:36]1

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 595964216-Amino-4-(1,2,3,4-tetrahydro-quinolin-6-yloxy)-pyrimidineHCID 67530371(4-Pyrrolidin-1-ylmethyl-3-trifluoromethyl-phenyl)-carbamic acid phenyl ester

Product 1

HCID 595963796-(6-Amino-pyrimidin-4-yloxy)-3,4-dihydro-2H-quinoline-1-carboxylic acid (4-pyrrolidin-1-ylmethyl-3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 85 mg (0.35 mMol) 6-amino-4-(1,2,3,4-tetrahydro-quinolin-6-yloxy)-pyrimidine (Step 1.3) and 0.33 mMol (4-pyrrolidin-1-ylmethyl-3-trifluoromethyl-phenyl)-carbamic acid phenyl ester in 2 ml DMSO is heated to 60° C. Then 65 μl (0.38 mMol) diisopropyl-ethyl-amine are added and stirring at 60° C. continued for 3 h. The resulting solution is poured into water containing 30 mg KOH and EtOAc, the aqueous layer separated off and extracted 2× with EtOAc. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated. Chromatography (Combi Flash; EtOAC→EtOAc/(EtOH+1.5% Et3N) 19:1) gives the title compound: MS: [M+1]+=513; HPLC: tARet=8.8; Anal.: C,H,N,F.

Workup

  1. customthe aqueous layer separated off
  2. extractionextracted 2× with EtOAc
  3. washThe organic phases are washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-23f083b4331b40de85faff349b0aa2dd
Source dataset
uspto-grants-2010_12
Patent number
US07855215B2

Reaction notes

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