Butylamine → ThyMidine, 2',3'-didehydro-3'-deoxy-, coMpd. with 1-Methyl-2-pyrrolidinone (1:1) (9CI)

HRID 975188Notes

Reaction equation

C(N)CCC.[CH3:6][C:7]1[C:13](=[O:14])[NH:12][C:10](=[O:11])[N:9]([C@@H:15]2[O:19][C@H:18]([CH2:20][O:21]C(C3C=CC=CC=3)=O)[CH:17]=[CH:16]2)[CH:8]=1.[CH3:30][N:31]1[CH2:35][CH2:34][CH2:33][C:32]1=[O:36]>C(OCCCC)(=O)C>[C@@H:15]1([N:9]2[CH:8]=[C:7]([CH3:6])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:19][C@H:18]([CH2:20][OH:21])[CH:17]=[CH:16]1.[CH3:30][N:31]1[CH2:35][CH2:34][CH2:33][C:32]1=[O:36]

Participants

Conditions

Temperature: 70 °C

Procedure

To n-butylamine (133 ml) was added 5'-benzoyl-d4T (7', 70.0 g). The reaction was heated at 70° C. for six hours. After cooling to 20°-25° C., N-methylpyrrolidinone (NMPO, 41.3 ml) and n-butyl acetate (350 ml) were added. Excess n-butylamine (~112.4 ml) along with 175 ml of n-butyl acetate was removed via vacuum distillation at 50° C. The resulting slurry was cooled to 20°-25° C. over one hour and stirred for 30 minutes. The slurry was then cooled to -10° to -15° C. and stirred for 1.5 hours. The cake was filtered and washed with 2×50 ml cold (-10° to -15° C.) n-butyl acetate and dried to give d4T.NMPO complex, 59.0 g (85.6%).

Workup

temperatureAfter cooling to 20°-25° C.
customExcess n-butylamine (~112.4 ml) along with 175 ml of n-butyl acetate was removed via vacuum distillation at 50° C
temperatureThe resulting slurry was cooled to 20°-25° C. over one hour
temperatureThe slurry was then cooled to -10° to -15° C.
stirringstirred for 1.5 hours
filtrationThe cake was filtered
washwashed with 2×50 ml cold (-10° to -15° C.) n-butyl acetate
customdried
customto give d4T

Sources & evidence

ORD record: ord-1859a926f365480c846af3a55a5a8648
Source dataset: uspto-grants-1997_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05608049

Reaction notes

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