Water → HCID 86674512, compound

HRID 869695Notes

Reaction equation

HRID 869695 reaction equation
[CH3:1][C:2]1[C:3]([C:12]2[CH:33]=[C:15]3[N:16]=[C:17]([N:27]4[CH2:31][CH2:30][CH:29]([OH:32])[CH2:28]4)[CH:18]=[C:19]([NH:20][CH:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[N:14]3[N:13]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[CH3:34][S:35](Cl)(=[O:37])=[O:36].C(N(CC)CC)C.O>ClCCl>[CH3:34][S:35]([O:32][C@H:29]1[CH2:30][CH2:31][N:27]([C:17]2[CH:18]=[C:19]([NH:20][CH:21]3[CH2:22][CH2:23][O:24][CH2:25][CH2:26]3)[N:14]3[N:13]=[C:12]([C:3]4[C:2]([CH3:1])=[N:11][C:10]5[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=5)[N:4]=4)[CH:33]=[C:15]3[N:16]=2)[CH2:28]1)(=[O:37])=[O:36]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 69932045HCID 69932045, compound

Product 1

HCID 86674512HCID 86674512, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-[2-(3-methylquinoxalin-2-yl)-7-(tetrahydro-2H-pyran-4-ylamino)pyrazolo[1,5-a]pyrimidin-5-yl]pyrrolidin-3-ol (200 mg, 0.449 mmol) and methanesulfonyl chloride (77 mg, 0.673 mmol) in dichloromethane (5.0 mL) was added triethylamine (0.125 mL, 0.898 mmol) at 0° C. After being stirred for 2 h, the reaction mixture was poured into water. The mixture was extracted with chloroform, and the organic layer was washed with saturated brine, dried over sodium sulfate, filtrated and concentrated in vacuo. The crude was purified by silica gel column chromatography (chloroform to chloroform:methanol=97:3) to give (3S)-1-[2-(3-methylquinoxalin-2-yl)-7-(tetrahydro-2H-pyran-4-ylamino)pyrazolo[1,5-a]pyrimidin-5-yl]pyrrolidin-3-yl methanesulfonate (the compound of Example 1.008 listed in the Table of Examples as described hereinafter). 1H-NMR (400 MHz, CDCl3): δ 1.73-1.83 (2H, m), 2.12-2.15 (2H, m), 2.30-2.39 (1H, m), 2.47-2.52 (1H, m), 3.04 (3H, s), 3.08 (3H, s), 3.56-3.63 (2H, m), 3.68-3.89 (4H, m), 3.99-4.02 (1H, m), 4.07-4.10 (2H, m), 5.19 (1H, s), 5.44-5.46 (1H, m), 6.20 (1H, d, J=8.2 Hz), 6.67 (1H, s), 7.70-7.77 (2H, m), 8.03-8.06 (1H, m), 8.16-8.19 (1H, m).

Workup

  1. extractionThe mixture was extracted with chloroform
  2. washthe organic layer was washed with saturated brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltrated
  5. concentrationconcentrated in vacuo
  6. customThe crude was purified by silica gel column chromatography (chloroform to chloroform:methanol=97:3)

Sources & evidence

ORD record
ord-ceea6438497142c8b4b0e0881a451c7c
Source dataset
uspto-grants-2015_03
Patent number
US08969376B2

Reaction notes

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