Water → HCID 178513728, compound

HRID 1503835Notes

Reaction equation

[C:1]([C:3]1[C:4]2[N:44](COCC[Si](C)(C)C)[CH:43]=[N:42][C:5]=2[C:6]([CH2:33][C:34]2[C:39]([Cl:40])=[CH:38][CH:37]=[CH:36][C:35]=2[Cl:41])=[N:7][C:8]=1[NH:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]2)=[CH:12][C:11]=1[C:29]([F:32])([F:31])[F:30])#[N:2].O.C(=O)(O)[O-:55].[Na+]>S(=O)(=O)(O)O>[Cl:41][C:35]1[CH:36]=[CH:37][CH:38]=[C:39]([Cl:40])[C:34]=1[CH2:33][C:6]1[C:5]2[N:42]=[CH:43][NH:44][C:4]=2[C:3]([C:1]([NH2:2])=[O:55])=[C:8]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]3)=[CH:12][C:11]=2[C:29]([F:31])([F:32])[F:30])[N:7]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of the product of Example 22B (150 mg, 0.2 mmol) in concentrated sulfuric acid (5 mL) was added water (1 mL) at 0° C. and the mixture was stirred at 95° C. for 20 minutes. After cooling to ambient temperature, water (3 mL) was added. The mixture was adjusted to pH 8-9 with saturated aqueous sodium bicarbonate solution and extracted with dichloromethane (3×20 mL). The organic layers were concentrated and the residue was purified by preparative HPLC using a gradient of 10/90 to 80/20 acetonitrile/water (containing 0.1% trifluoroacetic acid) to give the title compound. 1H NMR (DMSO-d6, 300 MHz): δ 13.51 (br, 1 H), 11.64 (s, 1 H), 9.52 (br, 1 H), 8.80 (s, 2 H), 8.61(s, 1 H), 7.81 (s, 1-H), 7.62 (d, J=9 Hz, 1 H), 7.56-7.53 (m, 2 H), 7.43-7.41 (m, 1 H), 7.07 (d, J=2.1 Hz, 1 H), 6.72 (dd, J=9, 2.1 Hz, 1 H), 4.83 (s, 2H), 2.75-2.67 (m, 8 H). MS: 564 (M+H+).

Workup

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

Sources & evidence

ORD record: ord-06bf1b8373b441759ffdb840fbe38d58
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09212192B2

Reaction notes

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