Hydrochloric Acid → HCID 178492173, compound

HRID 1621556Notes

Reaction equation

HRID 1621556 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[CH:14][C:13]([CH:16]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[OH:17])=[CH:12][C:11]=2[C:28]2[N:36]=[C:35]([CH3:37])[N:34]=[C:33]3[C:29]=2[N:30]=[CH:31][N:32]3C2CCCCO2)=[CH:5][CH:4]=1.Cl>CO.C(Cl)Cl>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[CH:14][C:13]([CH:16]([C:18]3[CH:19]=[CH:20][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:22][CH:23]=3)[OH:17])=[CH:12][C:11]=2[C:28]2[N:36]=[C:35]([CH3:37])[N:34]=[C:33]3[C:29]=2[N:30]=[CH:31][NH:32]3)=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 66599927HCID 66599927, compound

Product 1

HCID 178492173HCID 178492173, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

(6-(6-Methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)(4-(methylsulfonyl)phenyl)methanol (the crude material from the previous step) was suspended in MeOH (5.0 mL) and aqueous hydrochloric acid (5N, 0.50 mL, 2.5 mmol) was added. The reaction was stirred at room temperature for about 2 h, and then was diluted with DCM and MeOH. After 3.5 h, the suspension was filtered. Neither solid nor filtrate was >95% pure by HPLC, so they were combined, concentrated, treated with water, and filtered. The solid was collected, treated with DMSO and TFA, and filtered through a Celite® (diatomaceous earth) pad. The filtrate was purified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 min with a total flow rate of 100 mL/min.) to give (6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9H-purin-6-yl)pyridin-3-yl)(4-(methylsulfonyl)phenyl)methanol (122.4 mg, 56% yield over two steps). 1H NMR (d6-DMSO, 400 MHz) includes δ 12.62 (br s, 1H), 9.84 (br s, 1H), 8.62 (s, 1H), 8.52 (d, J=2.54 Hz, 1H), 8.29 (d, J=2.15 Hz, 1H), 8.16 (dd, J=8.71 Hz, 2.64 Hz, 1H), 7.90 (d, J=8.22 Hz, 2H), 7.73 (d, J=8.22 Hz, 2H), 6.84 (d, J=8.80 Hz, 1H), 5.91 (s, 1H), 3.84 (s, 3H), 3.17 (s, 3H), 2.84 (s, 3H). m/z (ESI, pos. ion) 518 (M+H)+.

Workup

  1. waitAfter 3.5 h
  2. filtrationthe suspension was filtered
  3. concentrationconcentrated
  4. additiontreated with water
  5. filtrationfiltered
  6. customThe solid was collected
  7. additiontreated with DMSO and TFA
  8. filtrationfiltered through a Celite® (diatomaceous earth) pad
  9. customThe filtrate was purified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 28 min with a total flow rate of 100 mL/min.)

Sources & evidence

ORD record
ord-54a9828e08d7422db1bd91b770785fd0
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

Loading…