(3R)-1-[3-(aminomethyl)phenyl]pyrrolidin-3-ol → 6-(4-Chlorophenyl)-3-{3-[(3R)-3-hydroxypyrrolidin-1-yl]benzyl}thieno[3,2-d]pyrimidin-4(3H)-one

HRID 2239335Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13]([O:15]C)=O)=[C:10](/[N:17]=[CH:18]/[N:19]([CH3:21])C)[CH:9]=2)=[CH:4][CH:3]=1.NC[C:24]1[CH:25]=[C:26]([N:30]2[CH2:34][CH2:33][C@@H:32]([OH:35])[CH2:31]2)[CH:27]=[CH:28][CH:29]=1>C1(O)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:12][C:11]3[C:13](=[O:15])[N:19]([CH2:21][C:28]4[CH:29]=[CH:24][CH:25]=[C:26]([N:30]5[CH2:34][CH2:33][C@@H:32]([OH:35])[CH2:31]5)[CH:27]=4)[CH:18]=[N:17][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 150 °C

Procedure

Methyl 5-(4-chlorophenyl)-3-{[(1E)-(dimethylamino)methylene]amino}thiophene-2-carboxylate (0.131 g, 0.41 mmol) and (3R)-1-[3-(aminomethyl)phenyl]pyrrolidin-3-ol (0.062 g, 0.26 mmol, purity 80%) in phenol (0.5 g) were subjected to microwave heating at 150° C. for 1 h. The product was precipitated with ether and decanted. The solid residue was washed with MeOH and CH2Cl2 to give 0.66 g (57%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.62 (s, 1H), 7.90 (s, 1H), 7.88 (d, 2H, J=8.7 Hz), 7.56 (d, 2H, J=8.7 Hz), 7.11 (t, 1H, J=7.9 Hz), 6.56-6.52 (m, 2H), 6.43 (d, 1H, J=7.5 Hz), 5.15 (s, 2H), 4.92 (d, 1H, J=7.5 Hz), 3.40-3.18 (m, 3H), 3.03 (bd, 1H, J=9-7 Hz), 2.07-1.95 (m, 1H), 1.91-1.82 (m, 1H). 13C NMR (100 MHz, DMSO-d6) δ 157.6, 156.1, 149.8, 149.6, 147.8, 137.4, 134.3, 131.3, 129.4, 127.9, 121.8, 121.7, 114.1, 110.9, 110.7, 69.2, 55.9, 48.9, 45.4, 33.6. MS (ESI+) 438.1 (M+1H+).

Workup

customThe product was precipitated with ether
customdecanted
washThe solid residue was washed with MeOH and CH2Cl2

Sources & evidence

ORD record: ord-73bb0037f39a4f768993bd3d9e3af755
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723331B2

Reaction notes

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