Formaldehyde → HCID 90241654, compound

HRID 1429495Notes

Reaction equation

[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:34])[CH2:13][NH:14][C:15](=[O:33])[CH2:16][O:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)[N:22]=[CH:21]2.[CH2:35](N(CC)CC)C.C=O.[BH3-]C#N.[Na+]>CO>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:34])[CH2:13][NH:14][C:15](=[O:33])[CH2:16][O:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([CH:27]1[CH2:32][CH2:31][N:30]([CH3:35])[CH2:29][CH2:28]1)[N:22]=[CH:21]2

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-2-((1-(piperidin-4-yl)-1H-indazol-5-yl)oxy)acetamide (50 mg, 0.108 mmol) in MeOH (5 mL) was added triethylamine (1 mL), HCHO (30%)(0.3 mL), and HOAC (0.4 mL). The mixture was stirred at 25° C. for 30 min, then NaBH3CN (0.4 mg) was added, and the mixture was stirred at 25° C. for an additional 1 h, concentrated under reduced pressure, and purified by prep-HPLC to give N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-2-((1-(1-methylpiperidin-4-yl)-1H-indazol-5-yl)oxy)acetamide (51.1 mg, yield 99%) as a colorless oil. 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.50 (br. s., 2H), 8.00 (s, 1H), 7.70 (d, J=8.78 Hz, 1H), 7.28-7.19 (m, 3H), 7.17-7.11 (m, 2H), 6.94 (dd, J=8.85, 1.82 Hz, 1H), 5.12 (s, 2H), 4.82 (br. s., 2H), 4.24-4.11 (m, 3H), 3.47-3.35 (m, 3H), 3.32 (br. s., 1H), 3.13-2.94 (m, 4H), 2.87 (s, 3H), 2.32-2.07 (m, 4H). LCMS (m/z): 478.3 [M+H]+

Workup

stirringthe mixture was stirred at 25° C. for an additional 1 h
concentrationconcentrated under reduced pressure
custompurified by prep-HPLC

Sources & evidence

ORD record: ord-31e36de0bd964a1eb712795c5c7293d8
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940726B2

Reaction notes

Loading…