Hydrogen Bromide → HCID 178479613, compound

HRID 2369897Notes

Reaction equation

[ClH:1].C[O:3][C:4]1[C:15]2[C:16]3[N:8]([NH:9][CH2:10][C:11]=3[C@H:12]([CH:18]3[CH:23]4[CH2:24][CH2:25][N:20]([CH2:21][CH2:22]4)[CH2:19]3)[C:13](=[O:17])[CH:14]=2)[CH:7]=[CH:6][N:5]=1.Br>C(O)(=O)C.CO>[ClH:1].[OH:3][C:4]1[C:15]2[C:16]3[N:8]([NH:9][CH2:10][C:11]=3[C@H:12]([CH:18]3[CH:23]4[CH2:24][CH2:25][N:20]([CH2:21][CH2:22]4)[CH2:19]3)[C:13](=[O:17])[CH:14]=2)[CH:7]=[CH:6][N:5]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of (S)-4-methoxy-7-(quinuclidin-3-yl)-8,9-dihydro-[1,4]diazepino[6,7,1-hi]indazol-6(7H)-one (200 mg, 0.6 mmol) from Step K of Example 10 in acetic acid (5 mL) was added 48% aqueous hydrogen bromide (5 ml) and the mixture was heated to 100° C. for 3 days. After cooling to room temperature and diluting with methanol, the pH was adjusted to 8. The solvent was concentrated in vacuo and the residue was purified by prep HPLC. The product was then treated immediately with hydrochloric acid following the procedure described in Step G of Example 8 to afford (S)-4-hydroxy-7-(quinuclidin-3-yl)-8,9-dihydro-[1,4]diazepino[6,7,1-hi]indazol-6(7H)-one hydrochloride (43 mg, 21%) as an off-white solid: 1H NMR (500 MHz, CD3OD) δ 7.98 (s, 1H), 7.76 (dd, J=2.5 Hz, 1H), 7.32 (d, J=2.0 Hz, 1H), 4.71-4.60 (m, 3H), 4.12-3.98 (m, 2H), 3.83-3.68 (m, 3H), 3.41-3.34 (m, 3H), 2.54 (d, J=2.5 Hz, 1H), 2.29 (brs 1H), 2.27-2.10 (m, 2H), 2.10-1.99 (m, 1H); MS (ESI+) m/z 313 (M+H).

Workup

temperatureAfter cooling to room temperature
concentrationThe solvent was concentrated in vacuo
customthe residue was purified by prep HPLC
additionThe product was then treated immediately with hydrochloric acid following the procedure

Sources & evidence

ORD record: ord-6efc0bc9da194cb7983f203bb27b7735
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08710046B2

Reaction notes

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