Phosphorus oxychloride → HCID 66549902, compound

HRID 1410084Notes

Reaction equation

HRID 1410084 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].[N:30]1[CH:35]=[CH:34][N:33]=[CH:32][C:31]=1[NH2:36].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:36][C:31]4[CH:32]=[N:33][CH:34]=[CH:35][N:30]=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 78747AminopyrazineHCID 516892Sodium BicarbonateHCID 683795141-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acid

Product 1

HCID 66549902HCID 66549902, compoundYield 87.2%

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 (30 mg, 0.07 mmol) and pyrazin-2-amine (7 mg, 0.07 mmol) in pyridine (6 mL) was added POCl3 (0.2 mL, 2.19 mmol) at 0° C., the reaction mixture was stirred at room temperature for 15 hours, a sat. NaHCO3 solution was added slowly, the solvent was removed in vacuo, and water (5 mL) and methanol (3 mL) were added. The precipitate was collected by filtration and washed with water (3 mL) and methanol (3 mL) to afford 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(pyrazin-2-yl)piperidine-3-carboxamide (30 mg, 87.2%) as a brown solid. 1H NMR (300 MHz, DMSO): δ 10.87 (s, 1H), 9.62 (s, 1H), 9.30 (s, 1H), 8.83 (s, 1H), 8.39-8.33 (m, 2H), 7.61 (d, 1H, J=2.1 Hz), 7.31 (dd, 1H, J1=8.7 Hz, J2=2.4 Hz), 6.82 (d, 1H, J=8.4 Hz), 4.76 (d, 1H, J=11.4 Hz), 4.60 (d, 1H, J=12.3 Hz), 3.68 (s, 3H), 3.64 (s, 3H), 3.13 (t, 1H, J=10.8 Hz), 3.01-2.93 (m, 1H), 2.79-2.71 (m, 1H), 2.04-2.00 (m, 1H), 1.81-1.67 (m, 2H), 1.46-1.42 (m, 1H). LC-MS: 493 [M+H]+, tR=1.50 min. HPLC: 95.75% at 214 nm, 96.29% at 254 nm, tR=5.38 min.

Workup

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

Sources & evidence

ORD record
ord-23ee2839bef1458b9c3fe743a5d74e97
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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