Potassium Carbonate → HCID 117942177, compound

HRID 1499284Notes

Reaction equation

HRID 1499284 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:27][CH2:26][C:11]3([CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@H:13]([C:23]([OH:25])=[O:24])[CH2:12]3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([O:28][C@H:29]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][C:35]=2[N:41]2[CH:45]=[CH:44][C:43]([CH3:46])=[N:42]2)[C:30]([F:33])([F:32])[F:31])[N:3]=1.Cl.Cl[CH2:49][CH2:50][N:51]([CH3:53])[CH3:52].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:9][CH2:10][C:11]3([CH2:15][N:14]([C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:17])[C@H:13]([C:23]([O:25][CH2:49][CH2:50][N:51]([CH3:53])[CH3:52])=[O:24])[CH2:12]3)[CH2:26][CH2:27]2)[CH:5]=[C:4]([O:28][C@H:29]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][C:35]=2[N:41]2[CH:45]=[CH:44][C:43]([CH3:46])=[N:42]2)[C:30]([F:32])([F:31])[F:33])[N:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 117952392HCID 117952392, compound

Product 1

HCID 117942177HCID 117942177, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of (S)-8-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2-(tert-butoxycarbonyl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid (1.6 g, 2.45 mmol) in DMF (24 mL) were added (2-chloro-ethyl)-dimethyl-amine hydrochloride (535 mg, 3.7 mmol) and K2CO3 (1.0 g, 7.4 mmol), and the reaction mixture was heated at 65° C. for 16 h. Then the reaction was cooled to RT, partitioned between EtOAc and water, and extracted. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification via prep-HPLC column chromatography (CH2Cl2/MeOH/NH4OH) provided (S)-2-tert-butyl 3-(2-(dimethylamino)ethyl) 8-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as an off-white solid.

Workup

  1. temperatureThen the reaction was cooled to RT
  2. custompartitioned between EtOAc and water
  3. extractionextracted
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification via prep-HPLC column chromatography (CH2Cl2/MeOH/NH4OH)

Sources & evidence

ORD record
ord-4badd3369a0e4f63a2dc4e4b3032555d
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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