tert-butyl ((1S)-2-{4-[2-(6-amino-8-bromo-9H-purin-9-yl)ethyl]piperidin-1-yl}-1-methyl-2-oxoethyl)carbamate → tert-Butyl {(1S)-2-[4-(2-{6-amino-8-[(7-chloro-1,3-benzothiazol-2-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate

HRID 736674Notes

Reaction equation

HRID 736674 reaction equation
[Cl:1][C:2]1[C:10]2[S:9][C:8]([SH:11])=[N:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.C(O[K])(C)(C)C.[NH2:18][C:19]1[N:27]=[CH:26][N:25]=[C:24]2[C:20]=1[N:21]=[C:22](Br)[N:23]2[CH2:28][CH2:29][CH:30]1[CH2:35][CH2:34][N:33]([C:36](=[O:47])[C@@H:37]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH3:38])[CH2:32][CH2:31]1>CN(C=O)C>[NH2:18][C:19]1[N:27]=[CH:26][N:25]=[C:24]2[C:20]=1[N:21]=[C:22]([S:11][C:8]1[S:9][C:10]3[C:2]([Cl:1])=[CH:3][CH:4]=[CH:5][C:6]=3[N:7]=1)[N:23]2[CH2:28][CH2:29][CH:30]1[CH2:35][CH2:34][N:33]([C:36](=[O:47])[C@@H:37]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:44])([CH3:43])[CH3:45])[CH3:38])[CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 57850351tert-butyl ((1S)-2-{4-[2-(6-amino-8-bromo-9H-purin-9-yl)ethyl]piperidin-1-yl}-1-methyl-2-oxoethyl)carbamateHCID 178418922HCID 178418922, compoundHCID 1785277847-Chloro-2-mercaptobenzothiazole

Product 1

HCID 57850166tert-Butyl {(1S)-2-[4-(2-{6-amino-8-[(7-chloro-1,3-benzothiazol-2-yl)thio]-9H-purin-9-yl}ethyl)piperidin-1-yl]-1-methyl-2-oxoethyl}carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
130 °C

Procedure

To a suspension of 7-Chloro-2-mercaptobenzothiazole (0.020 g, 0.097 mmol) in DMF (2.0 mL) was added (CH3)3COK (0.011 g, 0.97 mmol) at room temperature and stirring continued for 30 min. To the above reaction mixture tert-butyl ((1S)-2-{4-[2-(6-amino-8-bromo-9H-purin-9-yl)ethyl]piperidin-1-yl}-1-methyl-2-oxoethyl)carbamate (0.040 g, 0.081 mmol) in (1 mL) of DMF was added at room temperature. The reaction mixture was heated to 130° C. for 6 h, at the end of this period solvent was evaporated and crude was purified by preparative HPLC [X-Terra prep-RP18 10 um, 19×250 mm (waters), Mobile phase: solvent A: Water HPLC grade containing 0.01% TFA, and solvent B: acetonitrile containing 0.01% TFA, general eluting gradient—solvent B 15% to 80 over 15 to 25 minutes run time]. After lyophilization of HPLC fractions to afford title product. 1H NMR δ (CD3OD), 8.35 (s, 1H), 7.85-7.82 (m, 1H), 7.50-7.40 (m, 2H), 4.40 (t, J=7.2 Hz, 2H), 4.00-3.90 (m, 2H), 1.80-1.70 (m, 4H), 1.21-1.15 (m, 6H), 1.15 (s, 9H), 1.10 (s, 3H); LC-MS [M+H]+ 617.1

Workup

  1. customwas evaporated
  2. customcrude was purified by preparative HPLC [X-Terra prep-RP18 10 um, 19×250 mm (waters), Mobile phase: solvent A: Water HPLC grade containing 0.01% TFA, and solvent B: acetonitrile containing 0.01% TFA, general eluting gradient—solvent B 15% to 80 over 15 to 25 minutes run time]

Sources & evidence

ORD record
ord-4cf9356bbe3149c49f62fc46c8a89263
Source dataset
uspto-grants-2009_09
Patent number
US07595401B2

Reaction notes

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