Cyclopropanemethanamine → 6[(2-{[(3R)-3-Hydroxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methylbenzo[b]thiophene-3-carboxylic acid (cyclopropylmethyl)amide

HRID 985334Notes

Reaction equation

HRID 985334 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([C:9]2[S:17][C:16]3[C:11](=[N:12][CH:13]=[CH:14][C:15]=3[O:18][C:19]3[CH:20]=[CH:21][C:22]4[C:26]([C:27]([OH:29])=O)=[C:25]([CH3:30])[S:24][C:23]=4[CH:31]=3)[CH:10]=2)=[O:8])[CH2:3]1.[NH2:32][CH2:33][CH:34]1[CH2:36][CH2:35]1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>>[CH:34]1([CH2:33][NH:32][C:27]([C:26]2[C:22]3[CH:21]=[CH:20][C:19]([O:18][C:15]4[CH:14]=[CH:13][N:12]=[C:11]5[CH:10]=[C:9]([C:7]([N:4]6[CH2:5][CH2:6][C@@H:2]([OH:1])[CH2:3]6)=[O:8])[S:17][C:16]=45)=[CH:31][C:23]=3[S:24][C:25]=2[CH3:30])=[O:29])[CH2:36][CH2:35]1

Participants

5

Reactant 4

HCID 75646CyclopropanemethanamineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 207677606-[(2-{[(3R)-3-Hydroxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methylbenzo[b]thiophene-3-carboxylic acid

Product 1

HCID 599908066[(2-{[(3R)-3-Hydroxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methylbenzo[b]thiophene-3-carboxylic acid (cyclopropylmethyl)amideYield 66.1%

Procedure

This material was prepared from the reaction of 6-[(2-{[(3R)-3-hydroxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methylbenzo[b]thiophene-3-carboxylic acid 126a (65 mg, 0.14 mmole) with (aminomethyl)cyclopropane (37 μL, 0.43 mmole), diisopropylethylamine (50 μL, 0.29 mmole), and HBTU (81 mg, 0.22 mmole) in a similar manner previously described for example 117 to give a pale yellow solid (47 mg, 46%). 1H NMR (DMSO-d6, 300 MHz) δ8.60 (1H, d, J=5.56 Hz), 8.49 (1H, t, J=5.68 Hz), 8.07, 8.01 (1H, s), 7.97 (1H, d, J=2.27 Hz), 7.84 (1H, d, J=8.59 Hz), 7.34 (1H, dd, J=2.27, 8.84 Hz), 6.78 (1H, d, J=5.31 Hz), 4.38, 4.33 (0.5H, br s), 4.01-3.93 (3H, m), 3.67-3.47 (2H, m), 3.20 (2H, t, J=6.19 Hz), 2.62 (3H, s), 2.07-1.81 (2H, m), 1.08 (1H, m), 0.46 (2H, m), 0.26 (2H, m).

Sources & evidence

ORD record
ord-2b4b0477ee344cf1a9947b44d1d4a0cf
Source dataset
uspto-grants-2005_03
Patent number
US06869962B2

Reaction notes

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