Diisopropylethylamine → (5R,7R)-4-(4-((S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoyl)-1,4-diazepan-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate

HRID 521388Notes

Reaction equation

HRID 521388 reaction equation
Cl.[N+:2]([C:5]1[CH:30]=[CH:29][C:8]([C:9]([O:11][C@H:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([N:21]4[CH2:27][CH2:26][CH2:25][NH:24][CH2:23][CH2:22]4)[C:15]=3[C@H:14]([CH3:28])[CH2:13]2)=[O:10])=[CH:7][CH:6]=1)([O-:4])=[O:3].[C:31]([O:35][C:36]([N:38]([CH:51]([CH3:53])[CH3:52])[CH2:39][CH:40]([C:44]1[CH:49]=[CH:48][C:47]([Cl:50])=[CH:46][CH:45]=1)[C:41](O)=[O:42])=[O:37])([CH3:34])([CH3:33])[CH3:32].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[N+:2]([C:5]1[CH:6]=[CH:7][C:8]([C:9]([O:11][C@H:12]2[C:16]3[N:17]=[CH:18][N:19]=[C:20]([N:21]4[CH2:27][CH2:26][CH2:25][N:24]([C:41](=[O:42])[C@@H:40]([C:44]5[CH:45]=[CH:46][C:47]([Cl:50])=[CH:48][CH:49]=5)[CH2:39][N:38]([C:36]([O:35][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:37])[CH:51]([CH3:52])[CH3:53])[CH2:23][CH2:22]4)[C:15]=3[C@H:14]([CH3:28])[CH2:13]2)=[O:10])=[CH:29][CH:30]=1)([O-:4])=[O:3]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 251786973-{[(tert-Butoxy)carbonyl](propan-2-yl)amino}-2-(4-chlorophenyl)propanoic acidHCID 67436383(5R,7R)-4-(1,4-Diazepan-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate hydrochloride

Product 1

HCID 67437824(5R,7R)-4-(4-((S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoyl)-1,4-diazepan-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoateYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(5R,7R)-4-(1,4-Diazepan-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate hydrochloride (61 mg, 0.140 mmol) and 3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (48 mg, 0.140 mmol) were suspended in dichloromethane (5 mL). N,N-Diisopropylethylamine (54 mg, 0.420 mmol) was then added. HBTU (53 mg, 0.140 mmol) was added, and the resultant solution was stirred at ambient for 16 hours. After this time, the reaction mixture was quenched by the addition of saturated sodium carbonate solution and then extracted twice with dichloromethane. The combined organic portions were dried over sodium sulfate, filtered, and concentrated. The residue thus obtained was purified by silica gel chromatography to give (5R,7R)-4-(4-((S)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoyl)-1,4-diazepan-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (50 mg, 50%). LCMS (APCI+) M+=721.1, Rt=4.51 min.

Workup

  1. customAfter this time, the reaction mixture was quenched by the addition of saturated sodium carbonate solution
  2. extractionextracted twice with dichloromethane
  3. dry with materialThe combined organic portions were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue thus obtained
  7. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-59a7c614a18c4957be2ebbcfa3fe79c0
Source dataset
uspto-grants-2016_05
Patent number
US09328091B2

Reaction notes

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