Hydrochloric Acid → 4-[4-((1R,2R)-2-amino-cyclopentyloxy)-5-trifluoromethyl-pyrimidin-2-ylamino]-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide

HRID 1258173Notes

Reaction equation

HRID 1258173 reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[OH:7].Cl.[H-].[Na+].Cl[C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]2[CH:38]=[CH:37][C:26]([C:27]([NH:29][CH:30]3[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]3)=[O:28])=[CH:25][C:24]=2[O:39][CH3:40])[N:13]=1>O1CCOCC1.O>[NH2:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[O:7][C:16]1[C:17]([C:18]([F:19])([F:21])[F:20])=[CH:12][N:13]=[C:14]([NH:22][C:23]2[CH:38]=[CH:37][C:26]([C:27]([NH:29][CH:30]3[CH2:31][CH2:32][N:33]([CH3:36])[CH2:34][CH2:35]3)=[O:28])=[CH:25][C:24]=2[O:39][CH3:40])[N:15]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 10464306rac-(1R,2R)-2-aminocyclopentan-1-olHCID 582009164-(4-chloro-5-trifluoromethyl-pyrimidin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide

Product 1

HCID 584508974-[4-((1R,2R)-2-amino-cyclopentyloxy)-5-trifluoromethyl-pyrimidin-2-ylamino]-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

(R,R)-2-aminocyclopentanol×HCl (155 mg) is added to a suspension of NaH (135.2 mg) in dioxane (0.75 mL) and stirred for 30 min at RT. Then 4-(4-chloro-5-trifluoromethyl-pyrimidin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide (250 mg) is added. After 18 h, H2O (50 mL) is added. The precipitate formed is filtered off, washed with H2O, dissolved in CH2Cl2 and extracted with aqueous KHSO4 solution (10%). The aqueous phase is made basic again with K2CO3 and extracted with CH2Cl2. The organic phase is dried on magnesium sulphate, filtered to remove the desiccant and the solvent is eliminated in vacuo.

Workup

  1. waitAfter 18 h
  2. customThe precipitate formed
  3. filtrationis filtered off
  4. washwashed with H2O
  5. dissolutiondissolved in CH2Cl2
  6. extractionextracted with aqueous KHSO4 solution (10%)
  7. extractionextracted with CH2Cl2
  8. customThe organic phase is dried on magnesium sulphate
  9. filtrationfiltered
  10. customto remove the desiccant

Sources & evidence

ORD record
ord-0188558b097749a9afef32a261f7895e
Source dataset
uspto-grants-2013_06
Patent number
US08466155B2

Reaction notes

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