Diisopropylethylamine → HCID 86706056, compound

HRID 2176220Notes

Reaction equation

HRID 2176220 reaction equation
[CH3:1][CH:2]([CH3:45])[C@H:3]([O:20][CH2:21][CH:22]([CH3:44])/[CH:23]=[CH:24]/[C:25]1[CH:34]=[C:33]2[C:28]([CH:29]=[CH:30][C:31]([C@H:35]([NH:37][S@@:38]([C:40]([CH3:43])([CH3:42])[CH3:41])=[O:39])[CH3:36])=[N:32]2)=[CH:27][CH:26]=1)[C:4]([NH:6][C@@H:7]([CH3:19])[C:8]([N:10]1[CH2:15][CH2:14][CH2:13][C@@H:12]([C:16]([OH:18])=[O:17])[NH:11]1)=[O:9])=[O:5].[CH:46](N(CC)C(C)C)(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F>CN(C)C1C=CN=CC=1.O1CCCC1>[CH3:46][O:17][C:16]([C@@H:12]1[CH2:13][CH2:14][CH2:15][N:10]([C:8](=[O:9])[C@@H:7]([NH:6][C:4](=[O:5])[C@@H:3]([O:20][CH2:21][CH:22]([CH3:44])/[CH:23]=[CH:24]/[C:25]2[CH:34]=[C:33]3[C:28]([CH:29]=[CH:30][C:31]([C@H:35]([NH:37][S@@:38]([C:40]([CH3:43])([CH3:42])[CH3:41])=[O:39])[CH3:36])=[N:32]3)=[CH:27][CH:26]=2)[CH:2]([CH3:45])[CH3:1])[CH3:19])[NH:11]1)=[O:18]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate MethanaminiumHCID 86706057HCID 86706057, compound

Product 1

HCID 86706056HCID 86706056, compoundYield 113.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A cooled (0° C.) solution of 34b (500.1 mg, 0.645 mmol) in tetrahydrofuran/water (30 mL, 5:1) was treated with lithium hydroxide monohydrate (100.4 mg, 2.393 mmol). After stirring at 0° C. for 45 minutes, the reaction was quenched with hydrogen chloride solution (2 M, 1.2 mL) and the volatiles were removed in vacuo. The residual trichloroethanol was azeotroped off with toluene, toluene/methanol (2×), toluene then dried in high vacuo. The white solid was triturated with diethyl ether (2×) to provide crude (S)-1-{(S)-2-[(S)-3-methyl-2-((E)-2-methyl-4-{2-[(R)-1-((R)-2-methyl-propane-2-sulfinylamino)-ethyl]-quinolin-7-yl}-but-3-enyloxy)-butyrylamino]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (LCMS (m/z) 644.4 [M+H], Tr=2.44 min) which was used without further purification. A cooled (0° C.) solution of crude (S)-1-{(S)-2-[(S)-3-methyl-2-((E)-2-methyl-4-{2-[(R)-1-((R)-2-methyl-propane-2-sulfinylamino)-ethyl]-quinolin-7-yl}-but-3-enyloxy)-butyrylamino]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (0.645 mmol), N,N-diisopropylethylamine (0.56 mL, 3.225 mmol) and 4-dimethylaminopyridine (7.9 mg, 0.064 mmol) in dry tetrahydrofuran (210 mL) was treated with 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (294.3 mg, 0.774 mmol). The reaction was allowed to slowly warm to room temperature. After 16 h, the reaction was quenched with anhydrous methanol (5 mL). The volatiles were removed in vacuo and the residue was purified by silica gel chromatography using a 50 g Isolute cartridge eluted with a continuous gradient of dichloromethane/methanol 1:0 to 9:1 to afford the title compound (482.0 mg) as an orange gum and as a 1:1 mixture of diastereoisomers. LCMS (m/z) 658.3 [M+H], Tr=2.68 min.

Workup

  1. customwas used without further purification
  2. customthe reaction was quenched with anhydrous methanol (5 mL)
  3. customThe volatiles were removed in vacuo
  4. customthe residue was purified by silica gel chromatography
  5. washeluted with a continuous gradient of dichloromethane/methanol 1:0 to 9:1

Sources & evidence

ORD record
ord-ed5567e82df84e3abcde2351fb03aabd
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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