Dimethyl 2-hydroxypropylphosphonate → Pelcitoclax

HRID 1478788Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:82]([CH3:84])[CH3:83])[C:10]([CH3:81])=[C:11]([S:77]([CH3:80])(=[O:79])=[O:78])[C:12]=2[C:13]2[CH:14]=[C:15]([N:20]3[CH2:25][CH2:24][N:23]([C:26]4[CH:31]=[CH:30][C:29]([NH:32][S:33]([C:36]5[CH:41]=[CH:40][C:39]([NH:42][C@@H:43]([CH2:62][S:63][C:64]6[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=6)[CH2:44][CH2:45][N:46]6[CH2:51][CH2:50][CH:49]([C:52]([O:54]C(P(=O)(O)O)CC)=[O:53])[CH2:48][CH2:47]6)=[C:38]([S:70]([C:73]([F:76])([F:75])[F:74])(=[O:72])=[O:71])[CH:37]=5)(=[O:35])=[O:34])=[CH:28][CH:27]=4)[CH2:22][CH2:21]3)[CH:16]=[C:17]([F:19])[CH:18]=2)=[CH:4][CH:3]=1.O[CH:86]([CH3:94])[CH2:87][P:88](=[O:93])([O:91]C)[O:89]C>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:82]([CH3:83])[CH3:84])[C:10]([CH3:81])=[C:11]([S:77]([CH3:80])(=[O:78])=[O:79])[C:12]=2[C:13]2[CH:14]=[C:15]([N:20]3[CH2:21][CH2:22][N:23]([C:26]4[CH:27]=[CH:28][C:29]([NH:32][S:33]([C:36]5[CH:41]=[CH:40][C:39]([NH:42][C@@H:43]([CH2:62][S:63][C:64]6[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=6)[CH2:44][CH2:45][N:46]6[CH2:47][CH2:48][CH:49]([C:52]([O:54][CH2:94][CH2:86][CH2:87][P:88](=[O:89])([OH:93])[OH:91])=[O:53])[CH2:50][CH2:51]6)=[C:38]([S:70]([C:73]([F:74])([F:76])[F:75])(=[O:71])=[O:72])[CH:37]=5)(=[O:35])=[O:34])=[CH:30][CH:31]=4)[CH2:24][CH2:25]3)[CH:16]=[C:17]([F:19])[CH:18]=2)=[CH:4][CH:3]=1

Participants

Reactant 2

HCID 10630927Dimethyl 2-hydroxypropylphosphonate

HCID 1317365291-((R)-(3-(4-(N-(4-(4-(3-(2-(4-chlorophenyl)-1-isopropyl-5-methyl-4-(methylsulfonyl)-1H-pyrrol-3-yl)-5-fluorophenyl)piperazin-1-yl)phenyl)sulfamoyl)-2-(trifluoromethylsulfonyl)phenylamino)-4-(phenylthio)butyl)piperidine-4-carbonyloxy)propylphosphonic acid

Product 1

HCID 76900653Pelcitoclax

Procedure

2-(1-((R)-(3-(4-(N-(4-(4-(3-(2-(4-chlorophenyl)-1-isopropyl-5-methyl-4-(methylsulfonyl)-1H-pyrrol-3-yl)-5-fluorophenyl)piperazin-1-yl)phenyl)sulfamoyl)-2-(trifluoromethylsulfonyl)phenylamino)-4-(phenylthio)butyl)piperidine-4-carbonyloxy)propylphosphonic acid (17). 17 was prepared from 13 and dimethyl 2-hydroxypropylphosphonate according to general procedure V. 1H NMR (300 MHz, CD3OD): δ 7.97 (d, J=2.1 Hz, 1H), 7.73 (d, J=9.2 Hz, 1H), 7.36-7.08 (m, 13H), 6.85-6.43 (m, 4H), 5.26 (s, 1H), 4.54-4.44 (m, 1H), 4.01 (s, 1H), 3.58-2.92 (m, 16H), 2.87 (s, 3H), 2.76 (s, 3H), 2.70-2.55 (m, 1H), 2.26-1.85 (m, 8H), 1.46 (d, J=7.1 Hz, 6H), 1.38 (d, J=5.9 Hz, 3H). MS (ESI): m/z 1281.34 (M+H)+.

Sources & evidence

ORD record: ord-4231bc90b5864cf0a13107914e45ed3a
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403856B2

Reaction notes

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