Diisopropylethylamine → HCID 178496572, compound

HRID 1403166Notes

Reaction equation

HRID 1403166 reaction equation
[NH:1]1[CH2:4][CH:3]([NH:5][C:6]2[CH:11]=[C:10]([N:12]3[C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=4[N:14]=[C:13]3[CH:21]([F:23])[F:22])[N:9]=[C:8]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:7]=2)[CH2:2]1.[CH3:30][O:31][CH:32]1[CH2:37][CH2:36][CH:35]([C:38]([OH:40])=[O:39])[CH2:34][CH2:33]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O.O>[F:23][CH:21]([F:22])[C:13]1[N:12]([C:10]2[N:9]=[C:8]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[N:7]=[C:6]([NH:5][CH:3]3[CH2:2][N:1]([C:38]([C@H:35]4[CH2:36][CH2:37][C@@H:32]([O:31][CH3:30])[CH2:33][CH2:34]4)=[O:39])[CH2:4]3)[CH:11]=2)[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[N:14]=1.[F:23][CH:21]([F:22])[C:13]1[N:12]([C:10]2[N:9]=[C:8]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:7]=[C:6]([NH:5][CH:3]3[CH2:2][N:1]([C:38]([C@H:35]4[CH2:34][CH2:33][C@H:32]([O:31][CH3:30])[CH2:37][CH2:36]4)=[O:40])[CH2:4]3)[CH:11]=2)[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[N:14]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 736153Rac-(1r,4r)-4-methoxycyclohexane-1-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86686813HCID 86686813, compound

Product 2

HCID 178496572HCID 178496572, compoundHCID 178496573HCID 178496573, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

N-(Azetidin-3-yl)-6-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-2-(morpholin-4-yl)pyrimidin-4-amine (100 mg) was dissolved in N,N-dimethylformamide (1 ml), and 4-methoxycyclohexanecarboxylic acid (43 mg), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (142 mg), and N,N-diisopropyl ethylamine (213 μL) were added thereto, followed by stirring at room temperature for 3 hours. The reaction mixture was added water (100 ml), followed by extraction with ethyl acetate (100 ml). The extracts were washed with water and saturated brine, and then dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and then the solvent was evaporated under reduced pressure. The residue was separated/purified by silica gel column chromatography (from hexane:ethyl acetate=50:50-0:100 to chloroform:methanol=100:0-80:20) to obtain [3-({6-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-2-(morpholin-4-yl)pyrimidin-4-yl}amino)azetidin-1-yl](cis-4-methoxycyclohexyl)methanone (26 mg) (Example 249-1) and [3-({6-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-2-(morpholin-4-yl)pyrimidin-4-yl}amino)azetidin-1-yl](trans-4-methoxycyclohexyl)methanone (7.1 mg) (Example 249-2).

Workup

  1. extractionfollowed by extraction with ethyl acetate (100 ml)
  2. washThe extracts were washed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe desiccant was removed by filtration
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was separated/purified by silica gel column chromatography (from hexane:ethyl acetate=50:50-0:100 to chloroform:methanol=100:0-80:20)

Sources & evidence

ORD record
ord-5d561f03492f40008206542ba5aaa679
Source dataset
uspto-grants-2014_12
Patent number
US08912180B2

Reaction notes

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