Hydrochloric Acid → (1S,2R,3S,4R)-3-{(4-fluorobenzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester

HRID 1751226Notes

Reaction equation

HRID 1751226 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[C@@H:11]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C@H:10]2[CH2:21][C@@H:7]1[CH2:8][CH2:9]2)=[O:5])[CH3:2].[CH3:22][S:23]([NH:26][C:27]1[CH:42]=[CH:41][C:30]2[NH:31][C:32]([CH2:37][C:38](O)=[O:39])=[N:33][S:34](=[O:36])(=[O:35])[C:29]=2[CH:28]=1)(=[O:25])=[O:24].Cl.CN(C)CCCN=C=NCC.Cl>CN(C)C=O.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C@H:6]1[C@@H:11]([N:12]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C:38](=[O:39])[CH2:37][C:32]2[NH:31][C:30]3[CH:41]=[CH:42][C:27]([NH:26][S:23]([CH3:22])(=[O:25])=[O:24])=[CH:28][C:29]=3[S:34](=[O:35])(=[O:36])[N:33]=2)[C@H:10]2[CH2:21][C@@H:7]1[CH2:8][CH2:9]2)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 248585392H-1,2,4-Benzothiadiazine-3-acetic acid, 7-[(methylsulfonyl)amino]-, 1,1-dioxideHCID 66658077(1S,2R,3S,4R)-3-(4-fluorobenzylamino)-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester

Product 1

HCID 66674926(1S,2R,3S,4R)-3-{(4-fluorobenzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of (1S,2R,3S,4R)-3-(4-fluorobenzylamino)-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester (100.6 mg, 0.345 mmol) in N,N-dimethylformamide (3.0 mL) was added (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1g, 120.8 mg, 0.362 mmol), 4-dimethylaminopyridine (10.6 mg, 0.086 mmol), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (70.9 mg, 0.362 mmol). After stirring at 25° C. for 12 h, the mixture was diluted with ethyl acetate and acidified with 1.0M aqueous hydrochloric acid solution to pH 1. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo, and dried under high vacuum to afford the crude product, (1S,2R,3S,4R)-3-{(4-fluorobenzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester, as a faintly yellow oil. The crude product was used in the next step without further purification. LC-MS (ESI) calcd for C27H31FN4O7S2 606.16, found 607.2 [M+H+].

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (2×20 mL)
  3. dry with materialThe combined organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-bc11499744834670b7fa624924aa0d84
Source dataset
uspto-grants-2015_10
Patent number
US09156832B2

Reaction notes

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