m-Anisoyl chloride → HCID 178490484, compound

HRID 2168240Notes

Reaction equation

HRID 2168240 reaction equation
Cl.[CH3:2][C:3]1[C:11]2[C:10]([N:12]3[CH2:17][CH2:16][CH:15]([NH2:18])[CH2:14][CH2:13]3)=[N:9][CH:8]=[N:7][C:6]=2[NH:5][CH:4]=1.CCN(C(C)C)C(C)C.[CH3:28][O:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33](Cl)=[O:34]>C(Cl)Cl>[CH3:28][O:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33]([NH:18][CH:15]1[CH2:16][CH2:17][N:12]([C:10]2[N:9]=[CH:8][NH:7][C:6]3=[N:5][CH:4]=[C:3]([CH3:2])[C:11]=23)[CH2:13][CH2:14]1)=[O:34]

Participants

5

Reactant 3

HCID 74374m-Anisoyl chlorideHCID 81531DiisopropylethylamineHCID 86710200HCID 86710200, compound

Product 1

HCID 178490484HCID 178490484, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidinamine hydrochloride D11 (70 mg) and DIPEA (0.159 mL, 0.908 mmol) in DCM (1 mL) was added 3-(methyloxy)benzoyl chloride (56.8 mg, 0.333 mmol) and the reaction stirred for 18 hours. The mixture was partitioned between DCM (4 mL) and aqueous sodium bicarbonate (4 mL). The organic phase was then washed with 2M HCl (4 mL) before it was dried (phase separator) and concentrated. The crude product was purified by MDAP but the product was not clean, so it was then purified by silica chromatography eluting 2-10% MeOH in DCM to give E24 (17 mg) as a white solid, 1H NMR (d6-DMSO) δ 11.53 (1H, s), 8.33 (1H, d), 8.22 (1H, s), 7.45 (1H, d), 7.41 (1H, s), 7.37 (1H, t), 7.08 (1H, d), 7.07 (1H, s), 4.12-3.99 (3H, m), 3.81 (3H, s), 3.04 (2H, t), 2.37 (3H, s), 1.94 (2H, d), 1.74 (2H, ddd), MS(ES+) 366 [M+H]+.

Workup

  1. customThe mixture was partitioned between DCM (4 mL) and aqueous sodium bicarbonate (4 mL)
  2. washThe organic phase was then washed with 2M HCl (4 mL) before it
  3. customwas dried (phase separator)
  4. concentrationconcentrated
  5. customThe crude product was purified by MDAP
  6. customso it was then purified by silica chromatography
  7. washeluting 2-10% MeOH in DCM
  8. customto give E24 (17 mg) as a white solid, 1H NMR (d6-DMSO) δ 11.53 (1H, s), 8.33 (1H, d), 8.22 (1H, s), 7.45 (1H, d), 7.41 (1H, s), 7.37 (1H, t), 7.08 (1H, d), 7.07 (1H, s), 4.12-3.99 (3H, m), 3.81 (3H, s), 3.04 (2H, t), 2.37 (3H, s), 1.94 (2H, d), 1.74 (2H, ddd), MS(ES+) 366 [M+H]+

Sources & evidence

ORD record
ord-ed5193a078e845159012d3b57ca24589
Source dataset
uspto-grants-2015_06
Patent number
US09045485B2

Reaction notes

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