Morpholine → HCID 178426981, compound

HRID 2168232Notes

Reaction equation

HRID 2168232 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7](Cl)=[O:8])[CH:3]=1.[N:10]1[C:15]2[NH:16][CH:17]=[CH:18][C:14]=2[C:13]([N:19]2[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21][CH2:20]2)=[N:12][CH:11]=1.N1CCOCC1>C(Cl)Cl.CN(C=O)C>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]([NH:25][CH:22]2[CH2:21][CH2:20][N:19]([C:13]3[N:12]=[CH:11][NH:10][C:15]4=[N:16][CH:17]=[CH:18][C:14]=34)[CH2:24][CH2:23]2)=[O:8])[CH:3]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 27368945-Methylisoxazole-3-carbonyl chlorideHCID 11564772HCID 11564772, compound

Product 1

HCID 178426981HCID 178426981, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

5-methyl-3-isoxazolecarbonyl chloride (0.029 g, 0.200 mmol) in DCM (1 mL) and DMF (0.5 mL) was added to a solution of 1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidinamine D2 (0.043 g) in DMF (1.5 mL) in the presence of polymer-supported morpholine (0.279 g, 0.600 mmol, loading 2.15 mmol/g). The reaction mixture was shaken overnight at room temperature. The morpholine resin was filtered off and washed with a DCM:DMF (1:1) mixture. The unreacted acid chloride was removed by filtration on a Si—NH2 cartridge [Biotage] eluting with a DCM:DMF 1:1 mixture, and then the solvents were removed in vacuo. The crude mixture was purified by MDAP using a formic acid method to afford E16 (23.4 mg); 1H NMR (d6-DMSO) δ 11.70 (1H, brs), 8.64 (1H, d), 8.14 (1H, s), 7.18 (1H, d), 6.59 (1H, d), 6.52 (1H, s), 4.71 (2H, dt), 4.12 (1H, m), 3.15 (2H, dt), 2.44 (3H, s), 1.85 (2H, m), 1.60 (2H, m), MS(ES+) 326 [M+H]+.

Workup

  1. filtrationThe morpholine resin was filtered off
  2. washwashed with a DCM:DMF (1:1) mixture
  3. customThe unreacted acid chloride was removed by filtration on a Si—NH2 cartridge [Biotage]
  4. washeluting with a DCM:DMF 1:1 mixture
  5. customthe solvents were removed in vacuo
  6. customThe crude mixture was purified by MDAP
  7. customto afford E16 (23.4 mg)

Sources & evidence

ORD record
ord-5288f9869aff44c8a44035d4bd05027d
Source dataset
uspto-grants-2015_06
Patent number
US09045485B2

Reaction notes

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