2-[1-Hydroxy-4-methyl-3-(methyl-{3-methyl-2-[(1-methyl-piperidine-2-carbonyl)-amino]-pentanoyl}-amino)-pentyl]-thiazole-4-carboxylic acid methyl ester → 2-[1-Hydroxy-4-methyl-3-(methyl-{3-methyl-2-[(1-methyl-piperidine-2-carbonyl)-amino]-pentanoyl}-amino)-pentyl]-thiazole-4-carboxylic acid

HRID 446180Notes

Reaction equation

HRID 446180 reaction equation
[Sn](O)(C)(C)C.C[O:7][C:8]([C:10]1[N:11]=[C:12]([CH:15]([OH:40])[CH2:16][CH:17]([N:21]([CH3:39])[C:22](=[O:38])[CH:23]([NH:28][C:29]([CH:31]2[CH2:36][CH2:35][CH2:34][CH2:33][N:32]2[CH3:37])=[O:30])[CH:24]([CH3:27])[CH2:25][CH3:26])[CH:18]([CH3:20])[CH3:19])[S:13][CH:14]=1)=[O:9]>ClC(Cl)C>[OH:40][CH:15]([C:12]1[S:13][CH:14]=[C:10]([C:8]([OH:9])=[O:7])[N:11]=1)[CH2:16][CH:17]([N:21]([CH3:39])[C:22](=[O:38])[CH:23]([NH:28][C:29]([CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][N:32]1[CH3:37])=[O:30])[CH:24]([CH3:27])[CH2:25][CH3:26])[CH:18]([CH3:20])[CH3:19]

Participants

4

Reactant 2

HCID 595159712-[1-Hydroxy-4-methyl-3-(methyl-{3-methyl-2-[(1-methyl-piperidine-2-carbonyl)-amino]-pentanoyl}-amino)-pentyl]-thiazole-4-carboxylic acid methyl esterHCID 178477787HCID 178477787, compound

Product 1

HCID 668397662-[1-Hydroxy-4-methyl-3-(methyl-{3-methyl-2-[(1-methyl-piperidine-2-carbonyl)-amino]-pentanoyl}-amino)-pentyl]-thiazole-4-carboxylic acidYield 88.1%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

Me3SnOH (496 mg, 2.74 mmol) was added to a 0.020 M solution of methyl ester 23 (175 mg, 0.343 mmol) in dichloroethane (17.0 mL). The reaction mixture was heated to 60° C. for 20 h and then concentrated. Column chromatography (100% CH2Cl2 to elute tin containing materials followed by 80:20:1 CH2Cl2:MeOH:NH4OH to elute the product) afforded 150 mg (88%) of 24 as an amorphous solid. The 1H NMR corresponds to a 6:1 mixture of rotamers, with the major isomer reported. [α]D23=−17.4 (c=1.0, MeOH). IR: 1276, 1368, 1471, 1616, 2874, 2961 cm−1. 1H NMR (500 MHz, d6-DMSO): δ 0.70 (m, 3H), 0.75-0.82 (m, 3H), 0.83-0.90 (m, 6H), 1.04-1.16 (m 1H), 1.17-1.28 (m, 2H), 1.37-1.55 (m, 3H), 1.56-1.72 (m, 3H), 1.73-1.91 (m, 3H), 2.00-2.24 (m, 2H), 2.22 (s, 3H), 2.84 (br s, 1H), 2.94-3.00 (m, 1H), 3.04 (s, 3H), 4.16-4.60 (br s, 1H), 4.49 (d, 1H, J=10.5), 4.56 (app t, 1H, J=9.0), 5.93-6.40 (br s, 1H), 8.05 (s, 1H), 8.25 (s, 1H). 13C NMR (125 MHz, d6-DMSO): δ 10.0, 14.7, 19.1, 19.5, 19.6, 21.8, 23.58, 23.62, 28.75, 28.8, 35.2, 36.7, 42.6, 52.3, 54.1, 67.1, 67.5, 126.7, 147.8, 162.2, 170.7, 172.0, 177.6. HRMS (FAB) calcd for C24H41N4O5S (M+H): 497.2798. Found: 497.2793.

Workup

  1. concentrationconcentrated
  2. washColumn chromatography (100% CH2Cl2 to elute tin containing materials
  3. washMeOH:NH4OH to elute the product)

Sources & evidence

ORD record
ord-3461a6d5d9b444a1b172225063db4d3f
Source dataset
uspto-grants-2013_07
Patent number
US08476451B2

Reaction notes

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