Methanol → 7-(((2RS,3SR)-1,3,4-trihydroxybutan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one

HRID 533181Notes

Reaction equation

HRID 533181 reaction equation
C(OC[N:10]1[C:18]2[C:17]([O:19]C(C)(C)C)=[N:16][CH:15]=[N:14][C:13]=2[C:12]([CH2:24][NH:25][CH:26]([CH2:34][O:35]COC)[CH:27]([OH:33])[CH2:28][O:29]COC)=[CH:11]1)C1C=CC=CC=1.B(Br)(Br)Br.CO>C(Cl)Cl>[OH:35][CH2:34][CH:26]([NH:25][CH2:24][C:12]1[C:13]2[N:14]=[CH:15][NH:16][C:17](=[O:19])[C:18]=2[NH:10][CH:11]=1)[CH:27]([OH:33])[CH2:28][OH:29]

Participants

5

Reactant 3

HCID 887MethanolHCID 25134Boron tribromideHCID 67024018(6RS,7SR)-7-((5-(benzyloxymethyl)-4-tert-butoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)-2,4,9,11-tetraoxadodecan-6-ol

Product 1

HCID 1360362067-(((2RS,3SR)-1,3,4-trihydroxybutan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The product from Example 1.5 (104 mg, 0.195 mmol) was stirred in DCM (10 ml) at −78° C. and boron tribromide (1.0M in DCM, 1.95 ml) added dropwise. The reaction was stirred at −78° C. for 45 minutes before addition of methanol (10 ml). The solvents were evaporated and the residue co-evaporated with methanol (2×). The residue was partitioned between water and DCM and the aqueous layer evaporated. The residue was stirred in methanolic ammonia for 10 minutes and then evaporated on to silica and purified by flash silica chromatography, eluting with 5:4.5:0.5 DCM:methanol:ammonia giving the title compound as a white solid (27 mg, 52%). 1H NMR (300 MHz, CDCl3) 2.76 (1H, q, J 5.2 Hz), 3.48 (1H, dd, J 6.3, 11.9 Hz), 3.60 (2H, m), 3.70 (2H, m), 3.85 (2H, ABq), 7.34 (1H, s), 7.78 (1H, s); 13C NMR (75 MHz, CDCl3) 40.2, 59.8, 59.8, 63.5, 71.2, 113.1, 117.5, 129.2, 142.4, 143.5, 155.4; m/z (ES+) 537 (2MH+, 20%), 269 (MH+, 100%); HRMS (ESI+) C11H16N4O4 requires 269.1241. found 269.1250. The product, compound 1.6, is a 1:1 mixture of the enantiomers of Examples 17 and 18 below.

Workup

  1. customThe solvents were evaporated
  2. customThe residue was partitioned between water and DCM
  3. customthe aqueous layer evaporated
  4. customevaporated on to silica
  5. custompurified by flash silica chromatography
  6. washeluting with 5:4.5:0.5 DCM
  7. additiona 1:1 mixture of the enantiomers of Examples 17 and 18 below

Sources & evidence

ORD record
ord-0c2ff33a969f430e83fb8362a68b92eb
Source dataset
uspto-grants-2014_10
Patent number
US08853224B2

Reaction notes

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