3-Amino-1-propanol → 6-[(2-{[(3R)-3-Methoxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methyl benzo[b]thiophene-3-carboxylic acid 3-hydroxypropylamide

HRID 985331Notes

Reaction equation

[CH3:1][O:2][C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]([C:10]2[S:18][C:17]3[C:12](=[N:13][CH:14]=[CH:15][C:16]=3[O:19][C:20]3[CH:21]=[CH:22][C:23]4[C:27]([C:28](O)=[O:29])=[C:26]([CH3:31])[S:25][C:24]=4[CH:32]=3)[CH:11]=2)=[O:9])[CH2:4]1.[NH2:33][CH2:34][CH2:35][CH2:36][OH:37].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>>[OH:37][CH2:36][CH2:35][CH2:34][NH:33][C:28]([C:27]1[C:23]2[CH:22]=[CH:21][C:20]([O:19][C:16]3[CH:15]=[CH:14][N:13]=[C:12]4[CH:11]=[C:10]([C:8]([N:5]5[CH2:6][CH2:7][C@@H:3]([O:2][CH3:1])[CH2:4]5)=[O:9])[S:18][C:17]=34)=[CH:32][C:24]=2[S:25][C:26]=1[CH3:31])=[O:29]

Participants

Reactant 4

HCID 90863-Amino-1-propanol

HCID 81531Diisopropylethylamine

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

HCID 599907666-[(2-{[(3R)-3-methoxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methylbenzo[b]thiophene-3-carboxylic acid

Product 1

HCID 599907596-[(2-{[(3R)-3-Methoxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methyl benzo[b]thiophene-3-carboxylic acid 3-hydroxypropylamideYield 23.3%

Procedure

This material was prepared from the reaction of 6-[(2-{[(3R)-3-methoxypyrrolidin-1-yl]carbonyl}thieno[3,2-b]pyridin-7-yl)oxy]-2-methylbenzo[b]thiophene-3-carboxylic acid 123b (130 mg, 0.278 mmole) with 3-amino-1-propanol (106 μL, 1.39 mmole), N,N-diisopropylethylamine (0.15 mL, 0.83 mmole), and HBTU (263 mg, 0.694 mmole) in a manner similar to that previously described for example 117 to give a yellow solid (34 mg, 23%). 1H NMR (DMSO-d6, 300 MHz) δ8.58 (1H, d, J=5.27 Hz), 8.36 (1H, t, J=5.65 Hz), 8.06 (1H, s), 7.96 (1H, d, J=2.07 Hz), 7.83 (1H, d, J=8.85 Hz), 7.33 (1H, dd, J=2.07, 8.85 Hz), 6.75 (1H, d, J=5.27 Hz), 4.51 (1H, t, J=5.18 Hz), 4.13-3.82 (3H, m), 3.62 (2H, m), 3.50 (2H, m), 3.39-3.30 (2H, m), 3.27, 3.24 (3H, s), 2.60 (3H, s), 2.18-1.93 (2H, m), 1.71 (2H, quintet, J=6.6 Hz).

Sources & evidence

ORD record: ord-c71cc7f8f2ef474c98da0140915bab0d
Source dataset: uspto-grants-2005_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06869962B2

Reaction notes

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