Diisopropylethylamine → HCID 178420803, compound

HRID 525284Notes

Reaction equation

HRID 525284 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:16]=[C:15]3[C:10]([N:11]=[CH:12][CH:13]=[N:14]3)=[C:9]([O:17][C@@H:18]3[CH2:23][CH2:22][C@H:21]([NH2:24])[CH2:20][CH2:19]3)[CH:8]=2)[CH2:3][CH2:2]1.CS([C:29]1[N:34]=[CH:33][CH:32]=[CH:31][N:30]=1)(=O)=O.CCN(C(C)C)C(C)C>>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:16]=[C:15]3[C:10]([N:11]=[CH:12][CH:13]=[N:14]3)=[C:9]([O:17][C@@H:18]3[CH2:23][CH2:22][C@H:21]([NH:24][C:29]4[N:34]=[CH:33][CH:32]=[CH:31][N:30]=4)[CH2:20][CH2:19]3)[CH:8]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 132892252-(Methanesulfonyl)pyrimidineHCID 178511707HCID 178511707, compound

Product 1

HCID 178420803HCID 178420803, compound

Conditions

Temperature
100 °C

Procedure

As shown in step 9-iv of Scheme 9, to a solution so (cis) 4-(7-morpholinoquinoxalin-5-yl)oxycyclohexanamine (415 mg, 1.264 mmol) and 2-methylsulfonylpyrimidine (400 mg, 2.53 mmol) was added DIEA (490 mg, 661 μL, 3.79 mmol) and the reaction mixture was sealed in a vessel and heated to 100° C. for 16 hours. After this time, the volatiles were removed under a stream of nitrogen gas and the crude residue dissolved in minimal amount of DCM. Purification by medium pressure silica gel chromatography (0-10% MeOH/DCM, 1% Et3N] produced N-((cis)-4-((7-morpholinoquinoxalin-5-yl)oxy)cyclohexyl)pyrimidin-2-amine containing triethylamine hydrochloride as an impurity. Dissolved product in DCM and stirred with a silica-supported amine (Silabond Amine® 40-63 μm). The scavenger mixture was filtered, concentrated under reduced pressure, and dried under high vacuum to provide N-((cis)-4-((7-morpholinoquinoxalin-5-yl)oxy)cyclohexyl)pyrimidin-2-amine (Compound 28, 435 mg): 1H-NMR (400 MHz, CDCl3) δ 8.68 (d, J=1.9 Hz, 1H), 8.61 (d, J=1.9 Hz, 1H), 8.27 (s, 1H), 8.26 (s, 1H), 6.94 (d, J=2.4 Hz, 1H), 6.90 (d, J=2.4 Hz, 1H), 6.50 (t, J=4.8 Hz, 1H), 4.78 (s, 1H), 4.08-3.97 (m, 1H), 3.94-3.86 (m, 4H), 3.37-3.28 (m, 4H), 2.20 (d, J=9.1 Hz, 2H), 1.95-1.85 (m, 6H).

Workup

  1. customthe reaction mixture was sealed in a vessel
  2. customAfter this time, the volatiles were removed under a stream of nitrogen gas
  3. dissolutionthe crude residue dissolved in minimal amount of DCM
  4. customPurification by medium pressure silica gel chromatography (0-10% MeOH/DCM, 1% Et3N]

Sources & evidence

ORD record
ord-938ace7297314eafa271e063bf64f49e
Source dataset
uspto-grants-2016_05
Patent number
US09340557B2

Reaction notes

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