Phosphoric Acid → HCID 67467025, compound

HRID 1429560Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[SH:9].C(OC([N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][C:24](O)=O)[CH2:19][CH2:18]1)=O)(C)(C)C.OP(O)(O)=O.S1(CCCC1)(=O)=O>CO>[Br:8][C:5]1[CH:6]=[CH:7][C:2]2[N:1]=[C:24]([CH2:23][CH:20]3[CH2:21][CH2:22][NH:17][CH2:18][CH2:19]3)[S:9][C:3]=2[CH:4]=1

Participants

Conditions

Temperature: 80 °C

Procedure

2-Amino-5-bromobenzenethiol (326 mg, 1.597 mmol), 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)acetic acid (480 mg, 1.973 mmol), PPA (115% as H3PO4) (1637 mg, 6.82 mmol), and sulfolane (3.9 mL) were placed in a microwave vial and heated carefully with vial open to air at 80° C. for 10 min. The vial was then sealed and heated in microwave at 140° C. for 20 min. The mixture was diluted with MeOH, and purified via preparative HPLC (PHENOMENEX® Axia 5u C18 30×100 mm, Flow rate: 40 mL, Solvent A: 90% H2O and 10% MeOH with 0.1% TFA, Solvent B: 90% MeOH and 10% H2O with 0.1% TFA. 20% to 100% B in 10 min gradient, stop at 12 min, the product RT=6.86 min) to afford Compound 41A as an orange solid (380 mg, 76% yield). 1H NMR (400 MHz, methanol-d3) δ 8.16 (d, J=1.9 Hz, 1H), 7.82 (d, J=8.7 Hz, 1H), 7.63 (dd, J=8.7, 1.8 Hz, 1H), 3.40 (d, J=12.8 Hz, 2H), 3.14 (d, J=7.1 Hz, 2H), 3.01 (t, J=12.2 Hz, 2H), 2.27 (tdt, J=11.2, 7.3, 3.5 Hz, 1H), 2.02 (d, J=12.6 Hz, 2H), 1.56 (td, J=14.9, 3.7 Hz, 2H). LCMS (m/z)=311 (M+H)+.

Workup

customThe vial was then sealed
temperatureheated in microwave at 140° C. for 20 min
custompurified via preparative HPLC (PHENOMENEX® Axia 5u C18 30×100 mm, Flow rate: 40 mL, Solvent A
waitstop at 12 min

Sources & evidence

ORD record: ord-fecb5025ff5d444dad6f2fad50e73829
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940716B2

Reaction notes

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