Acetic Anhydride → Acetic acid 4-methyl-1-(4-methylcarbamoyl-thiazol-2-yl)-3-(methyl-{3-methyl-2-[(1-methyl-piperidine-2-carbonyl)-amino]-pentanoyl}-amino)-pentyl ester

HRID 446182Notes

Reaction equation

HRID 446182 reaction equation
[OH:1][CH:2]([C:27]1[S:28][CH:29]=[C:30]([C:32](=[O:35])[NH:33][CH3:34])[N:31]=1)[CH2:3][CH:4]([N:8]([CH3:26])[C:9]([CH:11]([NH:16][C:17]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][N:20]1[CH3:25])=[O:18])[CH:12]([CH3:15])[CH2:13][CH3:14])=[O:10])[CH:5]([CH3:7])[CH3:6].[C:36](OC(=O)C)(=[O:38])[CH3:37]>N1C=CC=CC=1>[CH3:7][CH:5]([CH3:6])[CH:4]([N:8]([CH3:26])[C:9](=[O:10])[CH:11]([NH:16][C:17]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][N:20]1[CH3:25])=[O:18])[CH:12]([CH3:15])[CH2:13][CH3:14])[CH2:3][CH:2]([O:1][C:36](=[O:38])[CH3:37])[C:27]1[S:28][CH:29]=[C:30]([C:32](=[O:35])[NH:33][CH3:34])[N:31]=1

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 668396411-Methyl-piperidine-2-carboxylic acid [1-({1-[2-hydroxy-2-(4-methylcarbamoyl-thiazol-2-yl)-ethyl]-2-methyl-propyl}-methyl-carbamoyl)-2-methyl-butyl]-amide

Product 1

HCID 66839688Acetic acid 4-methyl-1-(4-methylcarbamoyl-thiazol-2-yl)-3-(methyl-{3-methyl-2-[(1-methyl-piperidine-2-carbonyl)-amino]-pentanoyl}-amino)-pentyl esterYield 72%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A 0.050 M solution of 25 (12.0 mg, 0.0235 mmol) in pyridine (0.500 mL) was cooled to 0° C., and acetic anhydride (18.0 μL, 0.188 mmol) was added. The reaction mixture was allowed to warm to rt over 2 h and was stirred at rt for 21 h. The solvent was removed under reduced pressure. Reverse-phase HPFC (20:80 to 100:0 MeCN:H2O) followed by lyophilization afforded 9.3 mg (72%) of 11 as an amorphous solid. The 1H NMR corresponds to a 23:1 mixture of rotamers, with the major isomer reported. [α]D23=−2.2 (c=0.6, MeOH). IR: 1221, 1498, 1549, 1643, 1755, 2937 cm−1. 1H NMR (500 MHz, MeOD): δ 0.80 (d, 3H, J=7.0 Hz), 0.92 (t, 3H, J=7.5 Hz), 0.98 (d, 3H, J=7.0 Hz), 1.02 (d, 3H, J=6.5 Hz), 1.13-1.22 (m, 1H), 1.24-1.34 (m, 1H), 1.49-1.67 (m, 4H), 1.72-1.78 (m, 2H), 1.79-1.91 (m, 2H), 2.07 (dt, 1, J=3.0, 11.5 Hz), 2.15 (s, 3H), 2.18 (s, 3H), 2.22-2.31 (m, 1H), 2.34-2.41 (m, 1H), 2.56 (dd, 1H, J=2.5, 11.0 Hz), 2.90-2.95 (m, 1H), 2.94 (s, 3H), 3.11 (s, 3H), 4.40-4.51 (br s, 1H), 4.74 (d, 1H, J=8.0 Hz), 5.70 (dd, 1H, J=2.5, 11.5 Hz), 8.14 (s, 1H). 13C NMR (125 MHz, MeOD) δ 11.2, 16.4, 20.4, 20.6, 20.9, 24.4, 25.6, 26.3, 26.4, 31.1, 31.7, 35.7, 37.7, 44.9, 54.9, 56.7, 70.6, 71.2, 125.0, 150.9, 163.9, 171.82, 171.83, 175.3, 175.6. HRMS (FAB) calcd for C27H46N5O5S (M+H): 552.3220. Found: 552.3218.

Workup

  1. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-e07762f6ab03412eba865daa04963400
Source dataset
uspto-grants-2013_07
Patent number
US08476451B2

Reaction notes

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