Hydrochloric Acid → 2-(morpholin-4-yl)-6-[[(3R)-piperidin-3-yl]amino]-5-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]-3,4-dihydropyrimidin-4-one

HRID 1507520Notes

Reaction equation

HRID 1507520 reaction equation
C[O:2][C:3]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[N:6]=[C:5]([NH:15][C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17]2)[C:4]=1[C:29]1[S:30][C:31]2[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][C:32]=2[N:33]=1.Cl>>[N:9]1([C:7]2[NH:8][C:3](=[O:2])[C:4]([C:29]3[S:30][C:31]4[CH:37]=[CH:36][C:35]([C:38]([F:40])([F:39])[F:41])=[CH:34][C:32]=4[N:33]=3)=[C:5]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]3)[N:6]=2)[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 89554303(3R)-tert-butyl 3-(6-methoxy-2-morpholino-5-(5-(trifluoromethyl)benzo[d]thiazol-2-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate

Product 1

HCID 1365088292-(morpholin-4-yl)-6-[[(3R)-piperidin-3-yl]amino]-5-[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]-3,4-dihydropyrimidin-4-one

Conditions

Temperature
80 °C

Procedure

(3R)-tert-butyl 3-(6-methoxy-2-morpholino-5-(5-(trifluoromethyl)benzo[d]thiazol-2-yl)pyrimidin-4-ylamino)piperidine-1-carboxylate (40.0 mg, 0.07 mmol, 1.00 equiv) was added to concentrated hydrochloric acid (3.0 mL, 12N). The resulting solution was stirred for 2 h at 80° C. in an oil bath. After concentrated under reducing pressure, the residue was washed with 30 mL of methanol. The solid was collected by filtration and dissolved in 5 ml of water. After adjusted the pH value to 11 with 1N sodium hydroxide (aq.), the solid was collected by filtration and dried in vacuo to provide the title compound as a yellow solid. 1H-NMR (400 MHz, DMSO-d6): δ ppm 1.58-1.86(m, 3H), 1.95-1.96(m, 1H), 2.58-2.67(m, 2H), 2.78-2.81(m, 1H), 3.11-3.13(m, 1H), 3.65-3.67 (m, 8H), 4.08-4.12(m, 1H), 7.445-7.466(d, J=8.4 Hz, 1H), 7.943-7.980(d, J=14.8 Hz, 1H), 8.072-8.092 (d, J=8.0 Hz, 1H), 10.347-10.364(m, 1H); MS m/z [M+H]+ (ESI): 481. IRAK4 IC50=70 nM

Workup

  1. concentrationAfter concentrated
  2. washthe residue was washed with 30 mL of methanol
  3. filtrationThe solid was collected by filtration
  4. dissolutiondissolved in 5 ml of water
  5. filtrationthe solid was collected by filtration
  6. customdried in vacuo

Sources & evidence

ORD record
ord-d66e891ddbeb4c61aaa0028971a79cc1
Source dataset
uspto-grants-2015_12
Patent number
US09221809B2

Reaction notes

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