Sodium borohydride → 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-(3-(trifluoromethoxy)phenyl) thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 63919Notes

Reaction equation

[Cl:1][C:2]1[CH:38]=[CH:37][C:5]([CH2:6][C:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:17][CH2:18][C:19](OCC)=[O:20])[C:12](=[O:24])[N:11]([CH3:25])[C:10]=3[S:9][C:8]=2[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([O:32][C:33]([F:36])([F:35])[F:34])[CH:27]=2)=[CH:4][CH:3]=1.[BH4-].[Na+]>CCO>[Cl:1][C:2]1[CH:38]=[CH:37][C:5]([CH2:6][C:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:17][CH2:18][CH2:19][OH:20])[C:12](=[O:24])[N:11]([CH3:25])[C:10]=3[S:9][C:8]=2[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([O:32][C:33]([F:34])([F:35])[F:36])[CH:27]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of ethyl 3-(5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-6-(3-(trifluoromethoxy)phenyl)-1,2-dihydrothieno[2,3-d]pyrimidin-3(4H)-yl)propanoate (51 mg, 0.09 mmol) in EtOH (2 mL) was added NaBH4 (10.2 mg, 0.27 mmol). The reaction was heated at 50° C. for 18 h, cooled to RT, quenched with aq. HCl (0.1N, 2 mL) then concentrated to a residue which was purified by Prep HPLC to give 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-(3-(trifluoromethoxy)phenyl) thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (8.9 mg, 29.7% yield) as a white solid. 1H NMR (CD3OD) δ: 7.54-7.50 (m, 1H), 7.39 (d, J=8.0 Hz, 2H), 7.31 (d, J=8.4 Hz, 2H), 7.26 (s, 1H), 7.18 (d, J=8.4 Hz, 2H), 7.01 (d, J=8.4 Hz, 2H), 4.34 (s, 2H), 4.04 (t, J=6.8 Hz, 2H), 3.58-3.55 (m, 5H), 1.84-1.80 (m, 2H). LCMS: MH+ 525 and TR=3.382 min.

Workup

temperaturecooled to RT
customquenched with aq. HCl (0.1N, 2 mL)
concentrationthen concentrated to a residue which
customwas purified by Prep HPLC

Sources & evidence

ORD record: ord-5668b134595340509ce26a7ec04bdb62
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09447114B2

Reaction notes

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