Phosphorus oxychloride → HCID 66550339, compound

HRID 1410085Notes

Reaction equation

HRID 1410085 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:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[C:36](=[O:40])[NH:35][C:34]2=[O:41].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]=[C:33]5[C:37](=[CH:38][CH:39]=4)[C:36](=[O:40])[NH:35][C:34]5=[O:41])=[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 729154-AminophthalimideHCID 516892Sodium BicarbonateHCID 683795141-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acid

Product 1

HCID 66550339HCID 66550339, compoundYield 40.2%

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-aminoisoindoline-1,3-dione (19 mg, 0.12 mmol) in pyridine (8 mL) was added POCl3 (0.3 mL, 3.23 mmol) at 0° C., the reaction mixture was stirred at room temperature for 4 hours, a sat. NaHCO3 solution was added slowly, the solvent was removed in vacuo, water (5 mL) and methanol (2 mL) were added. The precipitate was collected by filtration and washed with water (5 mL) and methanol (5 mL) to afford 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(1,3-dioxoisoindolin-5-yl)piperidine-3-carboxamide (27 mg, 40.0%) as an orange solid. 1H NMR (300 MHz, DMSO): δ 11.20 (s, 1H), 10.59 (s, 1H), 9.64 (s, 1H), 8.83 (s, 1H), 8.13 (s, 1H), 7.86-7.73 (m, 2H), 7.63 (s, 1H), 7.38-7.29 (m, 1H), 6.78 (s, 1H), 4.77 (d, 1H, J=12.0 Hz), 4.62 (d, 1H, J=12.3 Hz), 3.66 (s, 3H), 3.61 (s, 3H), 3.16-2.94 (m, 2H), 2.60-2.55 (m, 1H), 2.04-2.01 (m, 1H), 1.76-1.72 (m, 2H), 1.52-1.41 (m, 1H). LC-MS: 560 [M+H]+, tR=1.49 min. HPLC: 99.49% at 214 nm, 99.47% at 254 nm, tR=5.33 min.

Workup

  1. customthe solvent was removed in vacuo, water (5 mL) and methanol (2 mL)
  2. additionwere added
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with water (5 mL) and methanol (5 mL)

Sources & evidence

ORD record
ord-7c67484944194e339be8691280ad26f5
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

Loading…