Trimethyl phosphite → HCID 68851856, compound

HRID 229461Notes

Reaction equation

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

Participants

Reactant 2

HCID 8472Trimethyl phosphite

HCID 68851717HCID 68851717, compound

Product 1

HCID 68851856HCID 68851856, compound

Procedure

Reaction of 2-[3-(2-bromo-2-methylpropanoyl)-6-methoxy-1H-indazol-1-yl]-N-(3,3-dimethylbutyl)-N-ethylacetamide from the above with trimethyl phosphite using the procedure as described in Method I Step B Example 1 provided the title compound following RP-HPLC using 50-100% MeCN gradient without TFA. 1H NMR (CDCl3, 500 MHz) showed two amide rotomers in about 1.3:1 ratio:o Major rotomer: 7.65 (d, 8.7 Hz, 1H), 6.83 (dd, 9.0 & 2.1 Hz, 1H), 6.805 (d, 1.9 Hz, 1H), 5.15 (s, 2H), 3.88 (s, 3H), 3.55 (d, 11.2 Hz, 6H), 3.48 (q, 7.1 Hz, 2H), 3.32˜3.35 (m, 2H), 2.01 (d, 2.5 Hz, 3H), 1.83 (d, 3.5 Hz, 3H), 1.40˜1.44 (m, 2H), 1.14 (t, 7.1 Hz, 3H), 0.91 (s, 9H). Minor rotomer: 7.66 (d, 8.7 Hz, 1H), 6.83 (dd, 9.0 & 2.1 Hz, 1H), 6.77 (d, 1.8 Hz, 1H), 5.12 (s, 2H), 3.88 (s, 3H), 3.54 (d, 11.4 HZ, 6H), 3.41˜3.44 (m, 2H), 3.38 (q, 7.2 Hz, 2H), 2.01 (d, 2.5 Hz, 3H), 1.84 (d, 3.5 Hz, 3H), 1.56˜1.60 (m, 2H), 1.12 (t, 7.1 Hz, 3H), 1.00 (s, 9H). 13C NMR (CDCl3, 125 MHz): Major rotomer: 165.85, 160.95, 142.34, 140.22, 133.82 (d, JC-P=9.6 Hz), 125.87 (d, JC-P=6.7 Hz), 122.56, 118.22, 113.71, 90.89, 55.74, 54.685 (d, JC-P=5.8 Hz), 51.96, 42.99, 42.51, 41.05, 29.99, 29.46, 20.13, 18.75, 14.51; Minor rotomer: 165.71, 159.96, 142.45, 140.22, 133.88 (d, JC-P=9.6 Hz), 125.79 (d, JC-P=7.7 Hz), 122.60, 118.27, 113.51, 90.94, 55.74, 54.685 (d, JC-P=5.8 Hz), 51.18, 44.03, 42.82, 41.50, 29.96, 29.46, 20.18, 18.75, 13.21. LC-MS: 3.67 min. (m/Z=518.3, 496.3, 370.4).

Sources & evidence

ORD record: ord-c0cbc767a71e439d8fefad44bf98cd23
Source dataset: uspto-grants-2009_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07563816B2

Reaction notes

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