1,4-Dioxa-8-azaspiro(4.5)decane → N-[1-[6-(Diethylamino)-6-oxohexyl]-4-piperidinyl]-8-methoxy-4-[[4-[[[1-(phenylmethyl)-4-piperidinyl]amino]carbonyl]-phenyl]amino]-3-quinolinecarboxamide

HRID 1755934Notes

Reaction equation

HRID 1755934 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[N:11]=[CH:10][C:9]([C:13]([OH:15])=O)=[C:8]2[NH:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([NH:25][CH:26]2[CH2:31][CH2:30][N:29]([CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:28][CH2:27]2)=[O:24])=[CH:19][CH:18]=1.[NH2:39][CH:40]1[CH2:45][CH2:44][N:43]([CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][C:51]([N:53]([CH2:56][CH3:57])[CH2:54][CH3:55])=[O:52])[CH2:42][CH2:41]1.BrCCCCCC(N(CC)CC)=O.O1C2(CCNCC2)OCC1>O>[CH2:56]([N:53]([CH2:54][CH3:55])[C:51](=[O:52])[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46][N:43]1[CH2:44][CH2:45][CH:40]([NH:39][C:13]([C:9]2[CH:10]=[N:11][C:12]3[C:7]([C:8]=2[NH:16][C:17]2[CH:18]=[CH:19][C:20]([C:23]([NH:25][CH:26]4[CH2:27][CH2:28][N:29]([CH2:32][C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)[CH2:30][CH2:31]4)=[O:24])=[CH:21][CH:22]=2)=[CH:6][CH:5]=[CH:4][C:3]=3[O:2][CH3:1])=[O:15])[CH2:41][CH2:42]1)[CH3:57]

Participants

6

Reactant 4

HCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 106582956-Bromo-N,N-diethylhexanamideHCID 152897728-Methoxy-4-[[4-[[[1-(phenylmethyl)-4-piperidinyl]amino]carbonyl]phenyl]amino]-3-quinolinecarboxylic acidHCID 199184164-amino-N,N-diethyl-1-piperidinehexanamide

Product 1

HCID 19918421N-[1-[6-(Diethylamino)-6-oxohexyl]-4-piperidinyl]-8-methoxy-4-[[4-[[[1-(phenylmethyl)-4-piperidinyl]amino]carbonyl]-phenyl]amino]-3-quinolinecarboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

N-[1-[6-(Diethylamino)-6-oxohexyl]-4-piperidinyl]-8-methoxy-4-[[4-[[[1-(phenylmethyl)-4-piperidinyl]amino]carbonyl]-phenyl]amino]-3-quinolinecarboxamide was prepared as a hygroscopic solid (1.14 hydrate) by coupling 8-methoxy-4-[[4-[[[1-(phenylmethyl)-4-piperidinyl]amino]-carbonyl]phenyl]amino]-3-quinolinecarboxylic acid and 4-amino-N,N-diethylol-piperidinehexanamide as described for Example 17, Step 5. 4-amino-N,N-diethyl-1-piperidinehexanamide can be prepared from 6-bromo-N,N-diethylhexanamide (Step 1) and 1,4-dioxa-8-azaspiro[4.5]-decane as described in U.S. Pat. Nos. 3,875,165 and 4,816,464: mp 115°-120° C.; 1H NMR (Me2SO-d6, 400 MHz) δ 9.49 (s, 1 H), 8.77 (s, 1 H), 8.39 (d, J=7.5 Hz, 1 H), 8.00 (d, J=7.7 Hz, 1 H), 7.69 (d, J=8.7 Hz, 2 H), 7.56 (d, J=1 H) 7.40 (m, 1 H), 7.1-7.3 (m, 6 H), 6.87 (d, J=8.68 Hz, 2 H), 3.95 (s, 3 H), 3.7 (m, 1 H), 3.1-3.6 (m, 7 H), 2.6-2.9 (m, 4 H), 2.1-2.3 (m, 4 H), 1.98 (t, J=11.0 Hz, 2 H), 1.65-1.85 (m, 4 H), 1,1-1.6 (m, 12 H), 0.95-1.1 (doft, J=7.1Hz, 6H); Karl Fischer, 2.63% H2O

Sources & evidence

ORD record
ord-8803d0e5858d479dbfec747c6d544cd5
Source dataset
uspto-grants-1995_08
Patent number
US05438064

Reaction notes

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