Methanesulfonamide → HCID 90353846, compound

HRID 1773033Notes

Reaction equation

HRID 1773033 reaction equation
[O:1]=[S:2]1(=[O:49])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C@:11]23[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:12]2[C@@H:13]2[C@@:26]([CH3:29])([CH2:27][CH2:28]3)[C@@:25]3([CH3:30])[C@@H:16]([C@:17]4([CH3:42])[C@@H:22]([CH2:23][CH2:24]3)[C:21]([CH3:32])([CH3:31])[C:20]([CH2:33][CH2:34][C:35]([CH3:41])([CH3:40])[CH2:36][C:37](O)=[O:38])=[CH:19][CH2:18]4)[CH2:15][CH2:14]2)[CH2:4][CH2:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[CH3:83][S:84]([NH2:87])(=[O:86])=[O:85]>C(Cl)Cl>[O:49]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C@:11]23[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:12]2[C@@H:13]2[C@@:26]([CH3:29])([CH2:27][CH2:28]3)[C@@:25]3([CH3:30])[C@@H:16]([C@:17]4([CH3:42])[C@@H:22]([CH2:23][CH2:24]3)[C:21]([CH3:31])([CH3:32])[C:20]([CH2:33][CH2:34][C:35]([CH3:40])([CH3:41])[CH2:36][C:37]([NH:87][S:84]([CH3:83])(=[O:86])=[O:85])=[O:38])=[CH:19][CH2:18]4)[CH2:15][CH2:14]2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 72879MethanesulfonamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 78320688HCID 78320688, compound

Product 1

HCID 90353846HCID 90353846, compoundYield 27.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 5-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)-3,3-dimethylpentanoic acid (30 mg, 0.043 mmol) in DCM (2 mL) was treated with HATU (28.6 mg, 0.075 mmol), N,N-diisopropylethylamine (0.026 mL, 0.150 mmol), and methanesulfonamide (5.3 mg, 0.055 mmol). The reaction mixture was stirred at rt for 16 h. The mixture was concentrated and the crude product was purified by prep HPLC (Method 13) to afford 5-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)-3,3-dimethyl-N-(methylsulfonyl)pentanamide (9.1 mg, 23% yield). LC/MS m/e 776.5 (M+H)+, 2.34 min (ionization peak, no UV) (method 3). 1H NMR (500 MHz, DMSO-d6) δ 5.20 (d, J=5.1 Hz, 1H), 4.69 (s, 1H), 4.55 (br. s., 1H), 3.08 (br. s., 1H), 3.00-2.91 (m, 3H), 2.81 (d, J=2.6 Hz, 3H), 2.74 (s, 3H), 2.64-2.56 (m, 3H), 2.48 (d, J=5.5 Hz, 1H), 2.40-2.32 (m, 1H), 1.95-0.76 (m, 29H), 1.91 (s, 3H), 1.65 (s, 3H), 1.03 (s, 3H), 0.95 (s, 3H), 0.94 (s, 6H), 0.93 (s, 3H), 0.87 (s, 3H), 0.78 (s, 3H).

Workup

  1. concentrationThe mixture was concentrated
  2. customthe crude product was purified by prep HPLC (Method 13)

Sources & evidence

ORD record
ord-b833f01515854ee286c00e8a1c65b0e1
Source dataset
uspto-grants-2016_02
Patent number
US09249180B2

Reaction notes

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