Isopropyl iodide → benzyl 3-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)cyclobutyl)propanoate

HRID 511693Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:47]=[C:46]([O:48][CH3:49])[CH:45]=[CH:44][C:4]=1[CH2:5][NH:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@H:16]3[C@@H:20]4[O:21][C:22]([CH3:25])([CH3:24])[O:23][C@@H:19]4[C@@H:18]([CH2:26][NH:27][CH:28]4[CH2:31][CH:30]([CH2:32][CH2:33][C:34]([O:36][CH2:37][C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)=[O:35])[CH2:29]4)[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.C([O-])([O-])=O.[K+].[K+].I[CH:57]([CH3:59])[CH3:58]>CC#N>[CH3:1][O:2][C:3]1[CH:47]=[C:46]([O:48][CH3:49])[CH:45]=[CH:44][C:4]=1[CH2:5][NH:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@H:16]3[C@@H:20]4[O:21][C:22]([CH3:25])([CH3:24])[O:23][C@@H:19]4[C@@H:18]([CH2:26][N:27]([CH:57]([CH3:59])[CH3:58])[CH:28]4[CH2:31][CH:30]([CH2:32][CH2:33][C:34]([O:36][CH2:37][C:38]5[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=5)=[O:35])[CH2:29]4)[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1

Participants

Conditions

Temperature: 95 °C

Procedure

Benzyl 3-(3-((((3 aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)amino)cyclobutyl)propanoate (2.3 g, 3.43 mmol) was mixed with K2CO3 (3.3 g, 24 mmol) and 2-iodopropane (5.8 g, 34.3 mmol) in MeCN (25 mL) in a sealed tube, then heated to 95° C. with stirring for 20 h. The reaction mixture was filtered and rinsed with MeCN (30 mL), the filtrate was evaporated in vacuo to afford the desired compound (2.1 g, yield: 88%) as a white solid, which was used for next step without further purification. 1H NMR (500 MHz, MeOD): δH 8.13 (s, 1H), 7.35-7.29 (m, 5H), 7.18 (d, J=3.0 Hz, 1H), 7.13 (d, J=8.5 Hz, 1H), 6.64 (d, J=3.0 Hz, 1H), 6.53 (d, J=2.5 Hz, 1H), 6.41 (dd, J=8.5 and 2.5 Hz, 1H), 6.18 (d, J=2.5 Hz, 1H), 5.33-5.32 (m, 1H), 5.08-5.06 (m, 2H), 4.90-4.89 (m, 1H), 4.64 (s, 2H), 4.15-4.14 (m, 1H), 3.83 (s, 3H), 3.75 (s, 3H), 3.37-3.36 (m, 0.43H), 3.01-2.98 (m, 0.59H), 2.92-2.88 (m, 1H), 2.70-2.40 (m, 3H), 2.24-2.18 (m, 2H), 2.10-1.80 (m, 3H), 1.75-1.69 (m, 2H), 1.61-1.52 (m, 5H), 1.38 (s, 3H), 0.94 (d, J=6.5 Hz, 3H), 0.81-0.79 (m, 3H) ppm; LC-MS (m/z): 714.0 [M+1]+.

Workup

filtrationThe reaction mixture was filtered
washrinsed with MeCN (30 mL)
customthe filtrate was evaporated in vacuo

Sources & evidence

ORD record: ord-c615d28167484ebcb0c3c6375cb31c08
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096634B2

Reaction notes

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