2-(Tributylstannyl)-1,3-thiazole → 4-Amino-5-(thiazol-2-yl)-7-[2,3,5-tris-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine

HRID 633780Notes

Reaction equation

[NH2:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([C@@H:12]3[O:32][C@H:31]([CH2:33][O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[C@@H:22]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C@H:13]3[O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C:4]=2[N:5]=[CH:6][N:7]=1.C([Sn](CCCC)(CCCC)[C:47]1[S:48][CH:49]=[CH:50][N:51]=1)CCC>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[C:3]2[C:10]([C:47]3[S:48][CH:49]=[CH:50][N:51]=3)=[CH:9][N:8]([C@@H:12]3[O:32][C@H:31]([CH2:33][O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[C@@H:22]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C@H:13]3[O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

An argon purged mixture of the compound 4 from Step 1 (544 mg, 0.74 mmol), 2-(tributylstannyl)thiazole (554 mg, 1.48 mmol) and PdCl2(PPh3)2 (22 mg, 0.03 mmol) in DMF (3 ml) was stirred at 100° C. for 48 h. Volatiles were evaporated under diminished pressure, the residue was co-evaporated with water (3×), twice with MeOH, twice with hexane and then co-evaporated with silica from hexane. Column chromatography on silica (hexanes then hexanes/AcOEt, 10:1→6:1) afforded title compound 5 as foam (454 mg, 89%). 1H NMR (500.0 MHz, CDCl3): −0.36, −0.10, 0.11, 0.13, 0.17 and 0.18 (6×s, 6×3H, CH3Si); 0.74, 0.95 and 0.99 (3×s, 3×9H, (CH3)C); 3.79 (dd, 1H, Jgem=11.4, J5′b,4′=2.7, H-5′b); 3.96 (dd, 1H, Jgem=11.4, J5′a,4′=3.2, H-5′a); 4.11 (ddd, 1H, J4′,5′=3.9, 2.7, J4′,3′=1.8, H-4′); 4.23 (dd, 1H, =4.7, J3′,4′=1.8, H-3′); 4.55 (dd, 1H, J2′,1′=6.9, J2′,3′=4.7, H-2′); 5.96 (bs, 1H, NHaHb); 6.31 (d, 1H, J1′,2′=6.9, H-1′); 7.21 (d, 1H, J5,4=3.4, H-5-thiazolyl); 7.72 (d, 1H, J4,5=3.4, H-4-thiazolyl); 7.74 (s, 1H, H-6); 8.26 (s, 1H, H-2); 9.79 (bs, 1H, NHaHb). 13C NMR (125.7 MHz, CDCl3): −5.35, −5.33, −5.19, −4.65, −4.61 and −4.47 (CH3Si); 17.82, 18.13 and 18.57 (C(CH3)3); 25.61, 25.86 and 26.15 ((CH3)3C); 63.37 (CH2-5′); 73.03 (CH-3′); 76.26 (CH-2′); 86.28 (CH-4′); 87.01 (CH-1′); 100.52 (C-4a); 112.19 (C-5); 116.76 (CH-5-thiazolyl); 122.24 (CH-6); 141.71 (CH-4-thiazolyl); 151.57 (C-7a); 151.94 (CH-2); 157.52 (C-4); 163.53 (C-2-thiazolyl). MS (ESI) m/z 692 (M+H), 714 (M+Na). HRMS (ESI) for C32H58N5O4SSi3 [M+H] calcd: 692.3512. found: 692.3512.

Workup

customAn argon purged
customVolatiles were evaporated under diminished pressure

Sources & evidence

ORD record: ord-f6e5c84847ea492f84449e6f55454175
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321800B2

Reaction notes

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