Hydrochloric Acid → 2-[2-(morpholin-4-yl)-6-oxo-4-[[(3R)-piperidin-3-yl]amino]-1,6-dihydropyrimidin-5-yl]-1,3-benzothiazole-5-carboxamide

HRID 1507543Notes

Reaction equation

HRID 1507543 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]2[S:11][C:10]([C:12]3[C:13]([NH:26][C@@H:27]4[CH2:32][CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28]4)=[N:14][C:15]([N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)=[N:16][C:17]=3[O:18]C)=[N:9][C:8]=2[CH:40]=1)(=[O:3])[NH2:2].Cl>>[N:20]1([C:15]2[NH:16][C:17](=[O:18])[C:12]([C:10]3[S:11][C:7]4[CH:6]=[CH:5][C:4]([C:1]([NH2:2])=[O:3])=[CH:40][C:8]=4[N:9]=3)=[C:13]([NH:26][C@@H:27]3[CH2:32][CH2:31][CH2:30][NH:29][CH2:28]3)[N:14]=2)[CH2:21][CH2:22][O:23][CH2:24][CH2:25]1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 89554286tert-butyl (3R)-3-[[5-(5-carbamoyl-1,3-benzothiazol-2-yl)-6-methoxy-2-(morpholin-4-yl)pyrimidin-4-yl]amino]piperidine-1-carboxylate

Product 1

HCID 1365045252-[2-(morpholin-4-yl)-6-oxo-4-[[(3R)-piperidin-3-yl]amino]-1,6-dihydropyrimidin-5-yl]-1,3-benzothiazole-5-carboxamide

Procedure

Following the same procedure as in step 4 of Example 337 using tert-butyl (3R)-3-[[5-(5-carbamoyl-1,3-benzothiazol-2-yl)-6-methoxy-2-(morpholin-4-yl)pyrimidin-4-yl]amino]piperidine-1-carboxylate (70.0 mg, 0.12 mmol, 1.00 equiv) and cone. hydrochloric acid (4.0 mL). The crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, XBridge Shield RP18 OBD Column, 5 um, 19*150 mm,; mobile phase, water 0.03% NH3H2O and CH3CN (14% CH3CN up to 27% in 7 min, up to 100% in 2 min, down to 14% in 1 min); Detector, Waters 2489 254&220 nm to afford the title compound as a white solid. 1H-NMR(400 MHz, DMSO-d6) δ ppm 1.54-1.66(m, 2H), 1.75(m, 1H), 1.99(m, 1H), 2.61-2.73(m, 2H), 2.80-2.85(m, 1H), 3.14-3.16(m, 1H), 3.69(m, 8H), 4.15-4.16(m, 1H), 7.38(s, 1H), 7.75-7.77(m, 1H), 7.97-8.00(m, 1H), 8.08(s, 1H), 8.26(s, 1H), 10.77-10.79(d, J=7.6 Hz, 1H). MS m/z [M+H]+ (ESI): 456. IRAK4 IC50=10 nM

Workup

  1. customThe crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  2. waitup to 100% in 2 min
  3. waitdown to 14% in 1 min)

Sources & evidence

ORD record
ord-026a70b74f5346d9ad48a342372262c2
Source dataset
uspto-grants-2015_12
Patent number
US09221809B2

Reaction notes

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