Ammonia → 5-iodo-7-(2-C-methyl-beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 633784Notes

Reaction equation

HRID 633784 reaction equation
Cl[C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([C@@H:12]3[O:34][C@H:33]([CH2:35][O:36]C(=O)C4C=CC=CC=4)[C@@H:23]([O:24]C(=O)C4C=CC=CC=4)[C@@:13]3([CH3:45])[O:14]C(=O)C3C=CC=CC=3)[C:4]=2[N:5]=[CH:6][N:7]=1.[NH3:46]>O1CCOCC1>[NH2:46][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([C@@H:12]3[O:34][C@H:33]([CH2:35][OH:36])[C@@H:23]([OH:24])[C@@:13]3([CH3:45])[OH:14])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 89779566[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(4-chloro-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-4-methyloxolan-2-yl]methyl benzoate

Product 1

HCID 210697325-iodo-7-(2-C-methyl-beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 69%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of compound 10 from Step 1 (200 mg, 0.27 mmol) and aq ammonia (25% w/w, 3 ml) in dioxane (3 ml) was stirred in a sealed tube at 120° C. for 10 h. After cooling the volatiles were evaporated and crude product was purified by chromatography on silica (CHCl3→CHCl3MeOH, 8:2) and then re-purified by reverse phase chromatography (0→100% MeOH in water) to afford title compound 6 as white solid (76 mg, 69%). Compound was recrystallized from MeOH/MeCN. Mp 207° C. [α]20D −39.0 (c 0.274, MeOH). 1H NMR (600 MHz, DMSO-d6): 0.67 (s, 3H, CH3); 3.65 (ddd, 1H, Jgem=12.1, J5′b,OH=4.8, J5′b,4′=2.7, H-5′b); 3.81 (ddd, 1H, Jgem=12.1, J5′a,OH=4.8, J5′a,4′=2.0, H-5′a); 3.79 (ddd, 1H, J4′,3′=9.1, J4,5=2.7, 2.0, H-4′); 3.93 (bd, 1H, J3′,4′=9.1, H-3′); 5.14 (s, 1H, OH-2′); 5.16 (bs, 1H, OH-3′); 5.22 (t, 1H, JOH,5′=4.8, OH-5′); 6.10 (s, 1H, H-1′); 6.67 (bs, 2H, NH2); 7.82 (s, 1H, H-6); 8.10 (s, 1H, H-2). 13C NMR (151 MHz, DMSO-d6): 19.89 (CH3); 51.68 (C-5); 59.46 (CH2-5′); 71.76 (CH-3′); 78.87 (C-2′); 82.39 (CH-4′); 90.71 (CH-1′); 103.11 (C-4a); 126.81 (CH-6); 149.88 (C-7a); 152.23 (CH-2); 157.43 (C-4). IR (Mk): 3474, 3429, 3392, 3366, 1631, 1582, 1553, 1504, 1440, 1343, 1295, 1147, 1128, 1070, 1045, 789. MS (FAB): m/z 407 (M+H). HRMS (FAB) for C12H16H4O4 [M+H] calcd: 407.0216. found: 407.0225. Anal. Calcd for C12H15IN4O4: C, 35.48; H, 3.72; N, 13.79. Found: C, 35.37; H, 3.72; N, 13.39.

Workup

  1. temperatureAfter cooling the volatiles
  2. customwere evaporated
  3. customcrude product was purified by chromatography on silica (CHCl3→CHCl3MeOH, 8:2)
  4. customre-purified by reverse phase chromatography (0→100% MeOH in water)

Sources & evidence

ORD record
ord-0b79438301464e47bc5da6513a171b5f
Source dataset
uspto-grants-2016_04
Patent number
US09321800B2

Reaction notes

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