Triethylamine → 5-chloro-thiophene-2-carboxylic acid {(1S,2S,4R)-4-[2-cyano-4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-2-hydroxy-cyclopentyl}-amide

HRID 2244685Notes

Reaction equation

HRID 2244685 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][C:11]2=[O:16])=[CH:6][C:3]=1[C:4]#[N:5].C(N(CC)CC)C.[Cl:24][C:25]1[S:29][C:28]([C:30]([NH:32][C@@H:33]2[C@@H:37]([OH:38])[CH2:36][C@H:35]([C:39](O)=[O:40])[CH2:34]2)=[O:31])=[CH:27][CH:26]=1.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1>C(#N)C.CN(C=O)C>[C:4]([C:3]1[CH:6]=[C:7]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][C:11]2=[O:16])[CH:8]=[CH:9][C:2]=1[NH:1][C:39]([C@@H:35]1[CH2:34][C@H:33]([NH:32][C:30]([C:28]2[S:29][C:25]([Cl:24])=[CH:26][CH:27]=2)=[O:31])[C@@H:37]([OH:38])[CH2:36]1)=[O:40])#[N:5]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 534164642-Amino-5-(3-oxo-morpholin-4-YL)-benzonitrileHCID 58826452(1R,3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-hydroxy-cyclopentanecarboxylic acid

Product 1

HCID 588264555-chloro-thiophene-2-carboxylic acid {(1S,2S,4R)-4-[2-cyano-4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-2-hydroxy-cyclopentyl}-amideYield 2.3%

Reagents, catalysts & solvents 1

HCID 21891449acetonitrile N,N-dimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred suspension of 2-amino-5-(3-oxo-morpholin-4-yl)-benzonitrile (114 mg; example 21B) in acetonitrile/DMF 9:1 (5 ml) were added triethylamine (0.22 ml), (1R,3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-hydroxy-cyclopentanecarboxylic acid (198 mg) and BOP-Cl (174 mg). The reaction mixture was stirred at 80° C. overnight, then cooled to r.t. and concentrated. The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 9:1) to give 5-chloro-thiophene-2-carboxylic acid {(1S,2S,4R)-4-[2-cyano-4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-2-hydroxy-cyclopentyl}-amide (6 mg). Off-white solid. MS: 489.0 ([M+H]+).

Workup

  1. temperaturecooled to r.t.
  2. concentrationconcentrated
  3. customThe crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-7febea558f3c49188afc27699592fb93
Source dataset
uspto-grants-2010_03
Patent number
US07678917B2

Reaction notes

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