Triethylamine → methyl (2S)-2-[[4-[(2-amino-4-oxo-1H-pteridin-6-yl)methylamino]benzoyl]amino]-5-[2-[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]ethoxy]ethylamino]-5-oxopentanoate

HRID 530140Notes

Reaction equation

HRID 530140 reaction equation
[NH2:1][C:2]1[N:11]=[C:10]([OH:12])[C:9]2[C:4](=[N:5][CH:6]=[C:7]([CH2:13][NH:14][C:15]3[CH:33]=[CH:32][C:18]([C:19]([NH:21][C@H:22]([C:28]([O:30][CH3:31])=[O:29])[CH2:23][CH2:24][C:25](O)=[O:26])=[O:20])=[CH:17][CH:16]=3)[N:8]=2)[N:3]=1.C(N(CC)CC)C.[NH2:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][O:47][CH2:48][CH2:49][NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54].[B-](F)(F)(F)F.CN(C(ON1C(=O)C=CC=C1)=[N+](C)C)C>CN(C)C=O.C(OCC)C>[NH2:1][C:2]1[N:11]=[C:10]([OH:12])[C:9]2[C:4](=[N:5][CH:6]=[C:7]([CH2:13][NH:14][C:15]3[CH:33]=[CH:32][C:18]([C:19]([NH:21][C@H:22]([C:28]([O:30][CH3:31])=[O:29])[CH2:23][CH2:24][C:25](=[O:26])[NH:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][O:47][CH2:48][CH2:49][NH:50][C:51](=[O:57])[O:52][C:53]([CH3:55])([CH3:54])[CH3:56])=[O:20])=[CH:17][CH:16]=3)[N:8]=2)[N:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 9881394tert-butyl N-{2-[2-(2-aminoethoxy)ethoxy]ethyl}carbamateHCID 178501469(4S)-4-[[4-[(2-amino-4-oxo-1H-pteridin-6-yl)methylamino]benzoyl]amino]-5-methoxy-5-oxopentanoic acid

Product 1

HCID 178501466methyl (2S)-2-[[4-[(2-amino-4-oxo-1H-pteridin-6-yl)methylamino]benzoyl]amino]-5-[2-[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethoxy]ethoxy]ethylamino]-5-oxopentanoateYield 62%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To (S)-4-(4-((2-amino-4-hydroxypteridin-6-yl)methylamino)benzamido)-5-methoxy-5-oxopentanoic acid (240 mg, 0.53 mmol, crude), triethylamine (0.3 mL, 2.2 mmol), and tert-butyl 2-(2-(2-aminoethoxy)ethoxy)ethylcarbamate (150 mg, 0.60 mmol) in N,N-dimethylformamide (3 mL), 2-(2-pyridon-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (261 mg, 0.88 mmol) was added in one portion. The reaction was stirred at ambient temperature for 16 hours. After this time, the product was crashed out with diethyl ether and collected by suction filtration. The solids were washed with methylene chloride (30 mL) to afford crude (S)-methyl 18-(4-((2-amino-4-hydroxypteridin-6-yl)methylamino)benzamido)-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14-diazanonadecan-19-oate (225 mg, 62%) as an orange-brown solid, which was used in the next step without further purification: MM-APCI MS m/z=684 [M−H]−.

Workup

  1. filtrationcollected by suction filtration
  2. washThe solids were washed with methylene chloride (30 mL)

Sources & evidence

ORD record
ord-7b3e626eb0f043f2ac769bad96f64e5d
Source dataset
uspto-grants-2016_05
Patent number
US09352049B2

Reaction notes

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