Trifluoroacetic acid → N-(1-(4-(3-hydroxypyridin-2-yl)cyclohexyl)azetidin-3-yl)-2-((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide

HRID 1896805Notes

Reaction equation

HRID 1896805 reaction equation
[OH:1][C:2]1[C:3]([CH:8]2[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[NH:15]1[CH2:18][CH:17]([NH:19][C:20](=[O:37])[CH2:21][NH:22][C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[C:30]([C:33]([F:36])([F:35])[F:34])[CH:31]=3)[N:26]=[CH:25][N:24]=2)[CH2:16]1.C(O)(C(F)(F)F)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[OH:1][C:2]1[C:3]([CH:8]2[CH2:13][CH2:12][CH:11]([N:15]3[CH2:16][CH:17]([NH:19][C:20](=[O:37])[CH2:21][NH:22][C:23]4[C:32]5[C:27](=[CH:28][CH:29]=[C:30]([C:33]([F:34])([F:36])[F:35])[CH:31]=5)[N:26]=[CH:25][N:24]=4)[CH2:18]3)[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 585626334-(3-Hydroxy-pyridin-2-yl)-cyclohexanoneHCID 68003594N-(azetidin-3-yl)-2((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide

Product 1

HCID 54769746N-(1-(4-(3-hydroxypyridin-2-yl)cyclohexyl)azetidin-3-yl)-2-((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-(3-hydroxy-pyridin-2-yl)-cyclohexanone (as prepared in step C, 1 eq.) and N-(azetidin-3-yl)-2-((6-(trifluoromethyl)quinazolin-4-yl)amino)acetamide (as prepared in the previous step, tris TFA salt, 1 eq.) in DCM was added TEA (3 eq.). After stirring at room temperature 30 minutes, NaBH(OAc)3 (3 eq) was added and the mixture was stirred overnight. The reaction was quenched with saturated sodium bicarbonate solution and partially concentrated. Extraction with ethyl acetate followed by concentration of the organic layer in vacuo yielded a residue which was purified by flash chromatography (silica gel, 0-20% 7 N NH3-MeOH/Ethyl acetate) to afford the product as a solid, mixture of isomers.

Workup

  1. customas prepared in the previous step
  2. stirringthe mixture was stirred overnight
  3. customThe reaction was quenched with saturated sodium bicarbonate solution
  4. concentrationpartially concentrated
  5. extractionExtraction with ethyl acetate
  6. customyielded a residue which
  7. customwas purified by flash chromatography (silica gel, 0-20% 7 N NH3-MeOH/Ethyl acetate)
  8. customto afford

Sources & evidence

ORD record
ord-850ecea361f94d629f7578a7f81fa574
Source dataset
uspto-grants-2013_08
Patent number
US08518969B2

Reaction notes

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