Dimethylamine → 4-(5-Cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-({1-[2-(dimethylamino)pyrimidin-4-yl]piperidin-4-yl}methyl)benzamide

HRID 2093589Notes

Reaction equation

HRID 2093589 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16](=[O:37])[C:17]3[CH:22]=[CH:21][C:20]([C:23]4[O:24][C:25]5[C:31]([CH:32]([CH3:34])[CH3:33])=[CH:30][C:29]([C:35]#[N:36])=[CH:28][C:26]=5[N:27]=4)=[CH:19][CH:18]=3)[CH2:10][CH2:9]2)[CH:5]=[CH:4][N:3]=1.[CH3:38][NH:39][CH3:40]>>[C:35]([C:29]1[CH:30]=[C:31]([CH:32]([CH3:34])[CH3:33])[C:25]2[O:24][C:23]([C:20]3[CH:21]=[CH:22][C:17]([C:16]([NH:15][CH2:14][CH:11]4[CH2:12][CH2:13][N:8]([C:6]5[CH:5]=[CH:4][N:3]=[C:2]([N:39]([CH3:40])[CH3:38])[N:7]=5)[CH2:9][CH2:10]4)=[O:37])=[CH:18][CH:19]=3)=[N:27][C:26]=2[CH:28]=1)#[N:36]

Participants

3

Reactant 2

HCID 674DimethylamineHCID 25169790N-{[1-(2-Chloropyrimidin-4-yl)piperidin-4-yl]methyl}-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide

Product 1

HCID 251700104-(5-Cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-({1-[2-(dimethylamino)pyrimidin-4-yl]piperidin-4-yl}methyl)benzamideYield 48%

Procedure

A 5-ml microwave vial was charged with N-{[1-(2-chloropyrimidin-4-yl)piperidin-4-yl]methyl}-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide (31 mg, EXAMPLE 7) and dimethylamine (2M in tetrahydrofuran, 3 ml). The resultant mixture was heated to 130° C. for 15 min in a microwave reactor. The mixture was concentrated in vacuo and the residue purified via flash chromatography on a Biotage Horizon 25M column, eluting with 10 column volumes of 100% ethyl acetate, to provide the title compound (15 mg, 48%). Mass spectrum (ESI) 524.3 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.34 (d, J=8.2 Hz, 2H), 7.94 (m, 5H), 7.52 (s, 1H), 6.30 (t, J=5.8 Hz, 1H), 5.84 (d, J=6.0 Hz, 1H), 4.43 (d, J=10.8 Hz, 2H), 3.48 (sept, J=6.8 Hz, 1H), 3.45 (t, J=6.4 Hz, 2H), 3.13 (s, 3H), 2.84 (t, J=11.2 Hz, 2H), 1.93, (m, 3H), 1.46 (d, J=7.0 Hz, 6H), 1.37 (m, 2H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue purified via flash chromatography on a Biotage Horizon 25M column
  3. washeluting with 10 column volumes of 100% ethyl acetate

Sources & evidence

ORD record
ord-12f62958c5614b83b84723dda74abd8f
Source dataset
uspto-grants-2013_05
Patent number
US08445480B2

Reaction notes

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