Diisopropylethylamine → HCID 53358341, compound

HRID 1807306Notes

Reaction equation

HRID 1807306 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28](O)=[O:29])[CH:5]=[CH:6][CH:7]=1.[NH2:32][C:33]1[NH:37][C:36]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:35][CH:34]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.C1COCC1>[CH2:41]([O:40][C:38]([C:36]1[NH:37][C:33]([NH:32][C:28]([C@H:9]2[C@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:31])[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:26])([CH3:27])[CH3:25])[NH:10]2)=[O:29])=[CH:34][CH:35]=1)=[O:39])[CH3:42]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12066244Ethyl 5-Amino-1H-pyrrole-2-carboxylateHCID 59249226(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acid

Product 1

HCID 53358341HCID 53358341, compoundYield 16.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of chiral-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (200 mg, 0.428 mmol), ethyl 5-amino-1H-pyrrole-2-carboxylate (180 mg, 1.17 mmol), 2-(7-azabenzotriazol-1-yl)-n,n,n′,n′-tetramethyluronium hexafluorophosphate (HATU, 200 mg, 0.526 mmol) and iPr2NEt (0.4 mL, 2.29 mmol) in CH2Cl2 (4 mL) and THF (4 mL) was stirred at 25° C. for 16 hours. The mixture was then diluted with CH2Cl2 and washed with water. The organic phase was separated, then concentrated under reduced pressure. The compound was purified by RP-HPLC (20%-95% of acetonitrile/water) to afford chiral 5-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-1H-pyrrole-2-carboxylic acid ethyl ester (42 mg, 16.3%) as an off-white powder. HRMS (ES) m/z Calcd for C30H30Cl2F2N4O3+H [(M+H)+]: 603 736. found: 603.1736.

Workup

  1. washwashed with water
  2. customThe organic phase was separated
  3. concentrationconcentrated under reduced pressure
  4. customThe compound was purified by RP-HPLC (20%-95% of acetonitrile/water)

Sources & evidence

ORD record
ord-7eebd4feccf042638c324005d5ced276
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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