Diisopropylethylamine → tert-Butyl (4aR,7aS)-2-benzamido-7a-[3-[(5-fluoropyridine-2-carbonyl)amino]phenyl]-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazine-6-carboxylate

HRID 77578

Reaction equation

HRID 77578 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C@:8]23[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14][C@H:13]2[CH2:12][S:11][C:10]([NH:24][C:25](=[O:32])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:9]3)[CH:5]=[CH:6][CH:7]=1.[F:33][C:34]1[CH:35]=[CH:36][C:37]([C:40](O)=[O:41])=[N:38][CH:39]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)C(C)CN=C=NCC.C(N(C(C)C)CC)(C)C>ClCCl.C(=O)(O)[O-].[Na+].CN(C)C=O>[C:25]([NH:24][C:10]1[S:11][CH2:12][C@@H:13]2[CH2:14][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][C@:8]2([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:40]([C:37]3[CH:36]=[CH:35][C:34]([F:33])=[CH:39][N:38]=3)=[O:41])[CH:3]=2)[N:9]=1)(=[O:32])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 27628765-fluoropyridine-2-carboxylic AcidHCID 27960291-Hydroxybenzotriazole hydrateHCID 219312251-(2-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochlorideHCID 86762764tert-butyl (4aR,7aS)-7a-(3-aminophenyl)-2-benzamido-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazine-6-carboxylate

Product 1

HCID 86762763tert-Butyl (4aR,7aS)-2-benzamido-7a-[3-[(5-fluoropyridine-2-carbonyl)amino]phenyl]-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazine-6-carboxylateYield 89%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

A slurry of tert-butyl (4aR,7aS)-7a-(3-aminophenyl)-2-benzamido-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazine-6-carboxylate (93 mg, 0.21 mmol), 5-fluoropyridine-2-carboxylic acid (31.9 mg, 0.23 mmol), 1-hydroxybenzotriazole hydrate (56.7 mg, 0.41 mmol) and 1-(2-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (40 mg, 0.21 mmol) in dichloromethane (4 mL) containing dimethylformamide (1 ml) is treated with diisopropylethylamine (179.2 μL, 1.03 mmol) and the resulting mixture is stirred at room temperature overnight. The reaction mixture is diluted with dichloromethane (5 mL) and saturated aqueous sodium bicarbonate (15 mL). The organic layer is separated and washed with saturated aqueous sodium chloride (10 mL), dried over sodium sulfate, filtered, and the solvent removed in vacuo to give the crude title compound (105 mg, 89%). ES/MS (m/e): 576 (M+H).

Workup

  1. customThe organic layer is separated
  2. washwashed with saturated aqueous sodium chloride (10 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-fab49d5fda4d43b78d03e8e0c3bda205
Source dataset
uspto-grants-2014_09
Patent number
US08841293B1

Linked notes

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