Phosphorus oxychloride → HCID 178492179, compound

HRID 1410086Notes

Reaction equation

HRID 1410086 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]([OH:26])=O)[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[O:41][C:40]([SH:42])=[N:39][N:38]=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[O:41][C:40]([SH:42])=[N:39][N:38]=5)=[CH:35][CH:36]=4)=[O:26])[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 178507465HCID 178507465, compound

Product 1

HCID 178492179HCID 178492179, compoundYield 11.3%

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)-1,3,4-oxadiazole-2-thiol (23 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 6 hours, a sat. NaHCO3 solution was added slowly, the solvent was removed in vacuo, methanol (20 mL) were added and filtrated. The filtrate was collected, concentrated and purified by a silica column chromatography (silica gel 200-300 mesh, eluting with dichloromethane:methanol=40:1) to afford 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl)piperidine-3-carboxamide (8.0 mg, 11.3%) as a white solid. 1H NMR (300 MHz, DMSO): δ 10.42 (s, 1H), 9.67 (s, 1H), 8.86 (s, 1H), 7.86-7.78 (m, 4H), 7.66 (s, 1H), 7.35 (d, 1H, J=8.7 Hz), 6.81 (brs, 1H), 4.81 (d, 1H, J=11.7 Hz), 4.66 (d, 1H, J=13.2 Hz), 3.69 (s, 3H), 3.63 (s, 3H), 3.15-3.07 (m, 1H), 3.01-2.93 (m, 1H), 2.73-2.61 (m, 1H), 2.07-1.74 (m, 3H), 1.78-1.74 (m, 1H). LC-MS: 591 [M+H]+, tR=1.56 min. HPLC: 97.80% at 214 nm, 97.26% at 254 nm, tR=5.91 min

Workup

  1. customthe solvent was removed in vacuo, methanol (20 mL)
  2. additionwere 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=40:1)

Sources & evidence

ORD record
ord-db9d9c110b62436ba1501a9b436101e0
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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