Ninhydrin → (2S,3R)-diethyl 2-((5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)-3-hydroxysuccinate

HRID 533189Notes

Reaction equation

HRID 533189 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH2:15][C@@H:16]([C@@H:22]([OH:28])[C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:17]([O:19][CH2:20][CH3:21])=[O:18].C([C@@](C([O-])=O)(O)[C@@](CC)(O)C([O-])=O)C.[CH2:43]([O:50][CH2:51][N:52]1[C:60]2[C:59]([O:61][CH3:62])=[N:58][CH:57]=[N:56][C:55]=2[C:54]([CH:63]=O)=[CH:53]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.C1C=C2C(C(O)(O)C(=O)C2=CC=1)=O>ClCCCl.C(Cl)Cl.CCOC(C)=O>[CH2:43]([O:50][CH2:51][N:52]1[C:60]2[C:59]([O:61][CH3:62])=[N:58][CH:57]=[N:56][C:55]=2[C:54]([CH2:63][NH:15][C@@H:16]([C@@H:22]([OH:28])[C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:53]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

9

Reactant 5

HCID 10236NinhydrinHCID 5049666Sodium triacetoxyborohydrideHCID 10560159(2S,3R)-diethyl 2-amino-3-hydroxysuccinate2×HCID 29414057diethyl-L(+)-tartrateHCID 577250835-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidine-7-carbaldehyde

Product 1

HCID 25223290(2S,3R)-diethyl 2-((5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)-3-hydroxysuccinateYield 69.4%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Sodium triacetoxyborohydride (0.545 g, 2.57 mmol) was added to a solution of (2S,3R)-diethyl 2-amino-3-hydroxysuccinate (0.406 g, 1.978 mmol), the latter prepared from diethyl-L-tartrate by known methods (A. Breuning, R. Vicik and T. Schirmeister, Tetrahedron Asymm., 2003, 14, 3301 and Z. Tang, Z.-H. Yang, X.-H. Chen, L.-F. Cun, A.-Q. Mi, Y.-Z. Jiang and L.-Z. Gong, J. Am. Chem. Soc., 2005, 127, 9285) and 5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidine-7-carbaldehyde (0.588 g, 1.978 mmol) in 1,2-dichloroethane (30 ml) and the mixture stirred at rt for 1 h. Tlc (EtOAc) showed all amine to have gone (ninhydrin) but still some aldehyde present and a new main product in between. More (2S,3R)-diethyl 2-amino-3-hydroxysuccinate (121 mg) added. The mixture was stirred a further 3 h then diluted with CH2Cl2 and washed with aqueous sat. NaHCO3, dried and evaporated. The residue was chromatographed (EtOAc-hexanes, 9:1 then EtOAc) to give (2S,3R)-diethyl 2-((5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)-3-hydroxysuccinate (0.668 g, 1.373 mmol, 69.4% yield) as a pale yellow gum. [α]D21 −5.9 (c 0.54, EtOH). 1H NMR (CDCl3, 300 MHz), δ ppm, 8.55 (s, 1H), 7.34 (s, 1H), 7.33-7.23 (m, 5H), 5.70 (s, 2H), 4.62 (d, 1H, J 3.4 Hz), 4.48 (s, 2H), 4.23-4.15 (m, 5H), 4.10 (s, 3H), 3.99 (d, 1H, J 13.8 Hz), 3.85 (d, 1H, J 3.3 Hz), 2.25 (br. s, 2H, exchanged to D2O), 1.26 (t, 3H, J 7.1 Hz), 1.25 (t, 3H, J 7.1 Hz). 13C NMR (CDCl3, 75.5 MHz), δ ppm, 171.9 (C), 171.1 (C), 156.2 (C), 150.0 (CH), 149.8 (C), 136.9 (C), 130.9 (CH), 128.4 (CH), 127.9 (CH), 127.6 (CH), 116.1 (C), 77.0 (CH2), 72.0 (CH), 70.2 (CH2), 63.8 (CH), 61.4 (CH2), 61.3 (CH2), 53.5 (CH3), 42.6 (CH2), 14.1 (CH3). +ESMS Found 487.2174 (M+H)+ C24H31N4O7 requires 487.2193.

Workup

  1. washwashed with aqueous sat. NaHCO3
  2. customdried
  3. customevaporated
  4. customThe residue was chromatographed (EtOAc-hexanes, 9:1

Sources & evidence

ORD record
ord-f9c162ea644547bfb3c0e80070f0cb86
Source dataset
uspto-grants-2014_10
Patent number
US08853224B2

Reaction notes

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