Carbonic acid-guanidine (1:1) → (2-Chlorophenyl)-[4-(2,4-diaminoquinazolin-5-yloxymethyl)piperidin-1-yl]methanone

HRID 1015340Notes

Reaction equation

HRID 1015340 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[C:4]([N:6]1[CH2:11][CH2:10][CH:9]([CH2:12][O:13][C:14]2[CH:21]=[CH:20][CH:19]=[C:18](F)[C:15]=2[C:16]#[N:17])[CH2:8][CH2:7]1)=[O:5].C(=O)(O)O.[NH2:31][C:32]([NH2:34])=[NH:33]>>[Cl:1][C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[C:4]([N:6]1[CH2:7][CH2:8][CH:9]([CH2:12][O:13][C:14]2[CH:21]=[CH:20][CH:19]=[C:18]3[C:15]=2[C:16]([NH2:17])=[N:33][C:32]([NH2:34])=[N:31]3)[CH2:10][CH2:11]1)=[O:5]

Participants

3

Reactant 2

HCID 286947Carbonic acid-guanidine (1:1)HCID 669242352-[1-(2-Chlorobenzoyl)-piperidin-4-ylmethoxy]-6-fluoro-benzonitrile

Product 1

HCID 25002412(2-Chlorophenyl)-[4-(2,4-diaminoquinazolin-5-yloxymethyl)piperidin-1-yl]methanoneYield 29%

Procedure

The cyclization of 2-[1-(2-chlorobenzoyl)-piperidin-4-ylmethoxy]-6-fluoro-benzonitrile (219 mg, 0.6 mmol) and guanidine carbonate was carried out using Method Z to afford 70.6 mg of title compound (29% yield). 1HNMR (400 MHz, DMSO-d6) δ 7.52 (m, 1H), 7.43 (m, 3H), 7.36 (t, J=8.4 Hz, 1H), 7.2 (m, 2H), 6.77 (d, J=8.4 Hz, 1H), 6.57 (t, J=7.2 Hz, 1H), 6.0 (br s, 2H), 4.56 (br d, J=12 Hz, 1H), 4.03 (d, J=6 Hz, 2H), 3.28 (m, 1H), 3.05 (m, 1H), 2.85 (t, J=12.8 Hz, 1H), 2.23 (m, 1H), 1.91 (m, 1H), 1.72 (t, J=13.6 Hz, 1H), 1.33 (m, 2H). MS m/z (ESI) 412 (M−H)+.

Sources & evidence

ORD record
ord-f025acdb0e6c43acab79271326c68c6f
Source dataset
uspto-grants-2011_07
Patent number
US07985755B2

Reaction notes

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