Ammonium formate → (3-{[4-Amino-3-(1-cyclopentyl-pyrrolidin-3-ylamino)-benzene-sulfonyl]-isobutyl-amino}-1-benzyl-2-hydroxy-propyl)-carbamic acid hexahydrofuro[2,3-b]furan-3-yl ester

HRID 1716876Notes

Reaction equation

HRID 1716876 reaction equation
[O:1]1[CH:5]2[O:6][CH2:7][CH2:8][CH:4]2[CH:3]([O:9][C:10](=[O:51])[NH:11][CH:12]([CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:13]([OH:43])[CH2:14][N:15]([S:20]([C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-])=O)=[C:25]([NH:32][CH:33]3[CH2:37][CH2:36][N:35]([CH:38]4[CH2:42][CH2:41][CH2:40][CH2:39]4)[CH2:34]3)[CH:24]=2)(=[O:22])=[O:21])[CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:2]1.C([O-])=O.[NH4+]>[Pd].CC1CCCO1>[O:1]1[CH:5]2[O:6][CH2:7][CH2:8][CH:4]2[CH:3]([O:9][C:10](=[O:51])[NH:11][CH:12]([CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:13]([OH:43])[CH2:14][N:15]([S:20]([C:23]2[CH:28]=[CH:27][C:26]([NH2:29])=[C:25]([NH:32][CH:33]3[CH2:37][CH2:36][N:35]([CH:38]4[CH2:42][CH2:41][CH2:40][CH2:39]4)[CH2:34]3)[CH:24]=2)(=[O:21])=[O:22])[CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:2]1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 68511382(1-Benzyl-3-{[3-(1-cyclopentyl-pyrrolidin-3-ylamino)-4-nitro-benzenesulfonyl]-isobutyl-amino}-2-hydroxy-propyl)-carbamic acid hexahydro-furo[2,3-b]furan-3-yl ester

Product 1

HCID 68511253(3-{[4-Amino-3-(1-cyclopentyl-pyrrolidin-3-ylamino)-benzene-sulfonyl]-isobutyl-amino}-1-benzyl-2-hydroxy-propyl)-carbamic acid hexahydrofuro[2,3-b]furan-3-yl ester

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 73012-MethyltetrahydrofuranSolvent

Procedure

(1-Benzyl-3-{[3-(1-cyclopentyl-pyrrolidin-3-ylamino)-4-nitro-benzenesulfonyl]-isobutyl-amino}-2-hydroxy-propyl)-carbamic acid hexahydro-furo[2,3-b]furan-3-yl ester (12) (0.36 g, 0.50 mmol, 1 equiv), ammonium formiate (0.16 g, 2.50 mmol, 5 equiv) and palladium on charcoal (10%, 0.106 g, 1.00 mmol, 2 equiv) were suspended in 2-methyl-tetrahydro-furan. The solution was heated to reflux for 2 h. The catalyst was filtered over a bed of dicalite and the filtrate was evaporated under reduced pressure. The crude product was purified by column chromatography on elution with dichloro-methane:ammonia in methanol (7N) (99:1 to 97.5:2.5). The solvent was evaporated under reduced pressure. (0.10, 0.50 mmol, 29%). LRMS (ES+): m/z 700 [M+H]+; HPLC (system 1) (272 nm) tR 6.95 min, 94%; 1H-NMR (CDCl3) δ 0.89 (d, 3H, CH3), 0.92 (d, 3H, CH3), 1.39-2.10 (m, 17H, CH2, H4, CH and CH2 (7x)), 2.70-3.21 (m, 9H, CH2—N, CH2—N (isobutyl), CH, H3a, CH—NH and CH—N), 3.59-3.78 (m, 3H, CH, H5, CH, H2 and CH), 3.78-3.99 (m, 3H, CH, H2, CH, H5 and CH—OH), 4.32-4.43 (brs, 1H, NH), 4.60-4.76 (brs, 1H, NH), 4.90-5.08 (m, 1H, CH, H3), 5.62 (d, 1H, CH, H6a), 6.62 (d, 1H, CHarom), 6.87 (s, 1H, CHarom), 7.07 (dd, 1H, CHarom), 7.18 (d, 1H, OH), 7.22-7.31 (m, 5H, C6H5).

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 2 h
  3. filtrationThe catalyst was filtered over a bed of dicalite
  4. customthe filtrate was evaporated under reduced pressure
  5. customThe crude product was purified by column chromatography on elution with dichloro-methane
  6. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-ceb522af4697404aaf6b1c072b92abcd
Source dataset
uspto-grants-2010_09
Patent number
US07803836B2

Reaction notes

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