1,4-Dioxa-8-azaspiro(4.5)decane → HCID 9985807, compound

HRID 1177690Notes

Reaction equation

HRID 1177690 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH2:10][CH:11]([NH:15][C:16]([N:18]3[CH2:23][CH2:22][CH:21]([N:24]4[CH2:33][C:32]5[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=5)[NH:26][C:25]4=[O:34])[CH2:20][CH2:19]3)=[O:17])[C:12](O)=[O:13])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.C(N(CC)C(C)C)(C)C.[O:44]1[C:48]2([CH2:53][CH2:52][NH:51][CH2:50][CH2:49]2)[O:47][CH2:46][CH2:45]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C)C=O.C(Cl)Cl>[O:44]1[C:48]2([CH2:53][CH2:52][N:51]([C:12](=[O:13])[CH:11]([NH:15][C:16]([N:18]3[CH2:23][CH2:22][CH:21]([N:24]4[CH2:33][C:32]5[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=5)[NH:26][C:25]4=[O:34])[CH2:20][CH2:19]3)=[O:17])[CH2:10][C:6]3[CH:7]=[C:8]4[C:3](=[CH:4][CH:5]=3)[NH:2][N:1]=[CH:9]4)[CH2:50][CH2:49]2)[O:47][CH2:46][CH2:45]1

Participants

7

Reactant 4

HCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 10434480HCID 10434480, compound

Product 1

HCID 9985807HCID 9985807, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the 3-(1H-indazol-5-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid (95 mg, 0.21 mmol) and N,N-diisopropylethylamine (0.14 mL, 0.82 mmol) in dimethylformamide (5 mL) was added a solution of 1,4-dioxa-8-azaspiro[4,5]decane (32 mg, 0.23 mmol) and PyBOP® (107 mg, 0.21 mmol) in methylene chloride (5 mL). The reaction mixture was stirred for 16 h at room temperature. All solvent was removed using high vacuum. The residue was subjected to flash column chromatography using methylene chloride/methanol/triethylamine (93:5:2) to give the title compound as a white solid (67 mg, 56% yield). 1H-NMR (CDCl3, 500 MHz) δ 10.52 (s, 1H), 7.97 (s, 1H), 7.54 (s, 1H), 7.37 (d, J=8.6 Hz, 1H), 7.20 (d, J=10.7 Hz, 1H), 7.16 (t, J=7.2 Hz, 1H), 7.04 (d, J=7.6 Hz, 1H), 7.01 (s, 1H), 6.94 (t, J=8.6 Hz, 1 H), 6.67 (d, J=7.6 Hz, 1H), 5.64 (d, J=7.9 Hz, 1H), 5.16 (dd, J=15.0, 6.7 Hz, 1H), 4.56-4.49 (m, 1H), 4.25 (s, 2H), 4.11 (br t, J=15.6 Hz, 2H), 3.92-3.84 (m, 4H), 3.73-3.69 (m, 1H), 3.60-3.56 (m, 1H), 3.48-3.43 (m, 1H), 3.22-3.17 (m, 1H), 3.11 (d, J=6.7 Hz, 2H), 2.90-2.85 (m, 2H), 2.68-2.60 (m, 4H), 1.67-1.61 (m, 2H), 1.54-1.49 (m, 2H). Mass spec.: 588 (MH)+.

Workup

  1. customAll solvent was removed

Sources & evidence

ORD record
ord-57db8dfe92c149278241d8540477f98c
Source dataset
uspto-grants-2010_11
Patent number
US07842808B2

Reaction notes

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