Toluene → tert-Butyl (3S)-3-[({[6-chloro-2,4,8,18,22-pentaazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaen-12-yl]amino}carbonyl)amino]pyrrolidine-1-carboxylate

HRID 541761Notes

Reaction equation

HRID 541761 reaction equation
C(Cl)(Cl)=O.C1(C)C=CC=CC=1.[NH2:12][C@H:13]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]1.C(N(CC)CC)C.FC(F)(F)[C:34]([OH:36])=O.FC(F)(F)C(O)=O.[Cl:46][C:47]1[CH:48]=[N:49][C:50]2[NH:51][C:52]3[CH:53]=[N:54][CH:55]=[C:56]([CH:69]=3)[CH2:57][CH2:58][C:59]3[CH:67]=[C:63]([NH:64][C:65]=1[N:66]=2)[CH:62]=[CH:61][C:60]=3[NH2:68]>C1COCC1>[Cl:46][C:47]1[CH:48]=[N:49][C:50]2[NH:51][C:52]3[CH:53]=[N:54][CH:55]=[C:56]([CH:69]=3)[CH2:57][CH2:58][C:59]3[CH:67]=[C:63]([NH:64][C:65]=1[N:66]=2)[CH:62]=[CH:61][C:60]=3[NH:68][C:34]([NH:12][C@H:13]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]1)=[O:36]

Participants

7

Reactant 5

HCID 1140TolueneHCID 6371PhosgeneHCID 8471Triethylamine2×HCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylateHCID 866361696-Chloro-2,4,8,18,22-pentaazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaen-12-amine bis(trifluoroacetate)

Product 1

HCID 57961783tert-Butyl (3S)-3-[({[6-chloro-2,4,8,18,22-pentaazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaen-12-yl]amino}carbonyl)amino]pyrrolidine-1-carboxylateYield 61.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 20% phosgene in toluene (0.49 mL, 0.93 mmol) was added a solution of tert-butyl (3S)-3-aminopyrrolidine-1-carboxylate (38 mg, 0.20 mmol) and triethylamine (102 μL, 0.734 mmol) in THF (0.5 mL). The resulting solution was stirred for 2 hours then concentrated. To the isolated solids was added DCM (0.75 mL) followed by 6-chloro-2,4,8,18,22-pentaazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaen-12-amine bis(trifluoroacetate) (70 mg, 0.1 mmol) and triethylamine (73 μL, 0.52 mmol). The resulting mixture was stirred at room temperature overnight and concentrated. The residue was purified by flash column chromatography to yield the desired product (34 mg, 50%). LCMS calculated for C27H32ClN8O3(M+H)+: m/z=551.1.

Workup

  1. concentrationthen concentrated
  2. additionTo the isolated solids was added DCM (0.75 mL)
  3. stirringThe resulting mixture was stirred at room temperature overnight
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-e573a85c93f941d7bb6052b86e4ce5ae
Source dataset
uspto-grants-2014_10
Patent number
US08871753B2

Reaction notes

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