Water → HCID 178513730, compound

HRID 1503834Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([CH2:15][C:16]3[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:23])[C:12]3[N:24]=[CH:25][N:26](COCC[Si](C)(C)C)[C:11]=3[C:10]=2[C:35]#[N:36])[CH:5]=[CH:4][C:3]=1[N:37]1[CH2:42][CH2:41][N:40](C(OC(C)(C)C)=O)[CH2:39][CH2:38]1.O.C(=O)(O)[O-:52].[Na+]>S(=O)(=O)(O)O>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([CH2:15][C:16]3[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:23])[C:12]3[N:24]=[CH:25][NH:26][C:11]=3[C:10]=2[C:35]([NH2:36])=[O:52])[CH:5]=[CH:4][C:3]=1[N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of the product of Example 18C (100 mg, 0.14 mmol) in concentrated sulfuric acid (5 mL) was added water (1 mL) at 0° C. and the mixture was heated at 95° C. for 20 minutes. After cooling to ambient temperature, water (3 mL) was added, and the mixture was adjusted to pH 8-9 with saturated aqueous sodium bicarbonate and extracted with dichloromethane (3×20 mL). The combined organic phase was concentrated and the residue was purified by preparative HPLC using a gradient of 10/90 to 75/25 acetonitrile in water (containing 0.1% trifluoroacetic acid) to give the title compound. 1H NMR (DMSO-d6, 300 MHz): δ 13.62 (s, 1 H), 11.85 (s, 1 H), 9.62 (s, 1 H), 8.69 (s, 2 H), 8.61 (s, 1 H), 7.85 (br, 1 H), 7.58 (m, 1 H), 7.55 (m, 1 H), 7.52 (d, J=2.4 Hz, 1 H), 7.42-7.37 (m, 1 H), 7.15 (dd, J=9, 2.4 Hz, 1 H), 6.85 (d, J=9 Hz, 1 H), 4.74 (s, 2 H), 3.27 (m, 4 H), 2.08-1.70 (m, 4 H). MS: 530 (M+H+).

Workup

temperatureAfter cooling to ambient temperature
extractionextracted with dichloromethane (3×20 mL)
concentrationThe combined organic phase was concentrated
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-69716439fdaf47a1928d609de6c5ff78
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09212192B2

Reaction notes

Loading…