Phosphorus oxychloride → HCID 178492178, compound

HRID 1410087Notes

Reaction equation

HRID 1410087 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:29]=[CH:28][S:27][C:14]=3[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([C:24](O)=[O:25])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[NH2:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2[N:38]([CH3:43])[C:39]([SH:42])=[N:40][N:41]=2)=[CH:33][CH:32]=1.O=P(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:29]=[CH:28][S:27][C:14]=3[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([NH:30][C:31]4[CH:32]=[CH:33][C:34]([C:37]5[N:38]([CH3:43])[C:39]([SH:42])=[N:40][N:41]=5)=[CH:35][CH:36]=4)=[O:25])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 683795141-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acidHCID 178481689HCID 178481689, compound

Product 1

HCID 178492178HCID 178492178, compoundYield 33.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acid (50 mg, 0.12 mmol) and 5-(4-aminophenyl)-4-methyl-4H-1,2,4-triazole-3-thiol (25 mg, 0.12 mmol) in pyridine (10 mL) was added POCl3 (0.3 mL, 3.29 mmol) at 0° C., the reaction mixture was stirred at room temperature for 8 hours, a sat. NaHCO3 solution (15 mL) was added slowly, the solvent was removed in vacuo, dichloromethane (40 mL) was added and filtrated, the filtrate was collected, concentrated and purified by a silica column chromatography (silica gel 200-300 mesh, eluting with dichloromethane:methanol=50:1) to afford 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(4-(5-mercapto-4-methyl-4H-1,2,4-triazol-3-yl)phenyl)piperidine-3-carboxamide (24.0 mg, 33.1%) as a white solid. 1H NMR (300 MHz, DMSO): δ 13.88 (s, 1H), 10.34 (s, 1H), 9.68 (s, 1H), 8.87 (s, 1H), 7.82-7.66 (m, 5H), 7.38-7.35 (m, 1H), 6.83 (brs, 1H), 4.83 (d, 1H, J=12.0 Hz), 4.68 (d, 1H, J=11.7 Hz), 3.71 (s, 3H), 3.63 (s, 3H), 3.58 (s, 3H), 3.15-3.07 (m, 1H), 3.00-2.93 (m, 1H), 2.62-2.58 (m, 1H), 2.07-2.03 (m, 1H), 1.83-1.71 (m, 2H), 1.51-1.47 (m, 1H). LC-MS: 604 [M+H]+, tR=1.50 min. HPLC: 99.39% at 214 nm, 99.39% at 254 nm, tR=5.36 min.

Workup

  1. customthe solvent was removed in vacuo, dichloromethane (40 mL)
  2. additionwas added
  3. filtrationfiltrated
  4. customthe filtrate was collected
  5. concentrationconcentrated
  6. custompurified by a silica column chromatography (silica gel 200-300 mesh, eluting with dichloromethane:methanol=50:1)

Sources & evidence

ORD record
ord-0287707adea449909841f63d4abab76d
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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