Beta-Alanine → 5-fluoro-N2-(3-hydroxyphenyl)-N4-[1-oxo-1,2,3,6-tetrahydropyrimido[2,1-c][1,4]benzoxazin-9-yl]-2,4-pyrimidinediamine

HRID 71632

Reaction equation

HRID 71632 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([NH:11][C:12]3[C:17]([F:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=4)[N:13]=3)=[CH:10][C:5]=2[NH:4][C:3](=S)[CH2:2]1.[NH2:28][CH2:29][CH2:30][C:31](O)=[O:32]>>[F:18][C:17]1[C:12]([NH:11][C:9]2[CH:8]=[CH:7][C:6]3[O:1][CH:2]=[C:3]4[NH:28][CH2:29][CH2:30][C:31](=[O:32])[N:4]4[C:5]=3[CH:10]=2)=[N:13][C:14]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=2)=[N:15][CH:16]=1

Participants

3

Reactant 2

HCID 239Beta-AlanineHCID 22060561N4-[2H-1,4-benzoxazin-3 (4H)-thione-6-yl]-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine

Product 1

HCID 220611505-fluoro-N2-(3-hydroxyphenyl)-N4-[1-oxo-1,2,3,6-tetrahydropyrimido[2,1-c][1,4]benzoxazin-9-yl]-2,4-pyrimidinediamine

Procedure

In a manner analogous to the preparation of N4-[2,4-dihydro-1-oxo-4H-imidazo[2,1-c][1,4]benzoxazin-8-yl]-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine, N4-[2H-1,4-benzoxazin-3(4H)-thione-6-yl]-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine (400 mg, 1.04 mmol) and β-alanine (500 mg) gave 5-fluoro-N2-(3-hydroxyphenyl)-N4-[1-oxo-1,2,3,6-tetrahydropyrimido[2,1-c][1,4]benzoxazin-9-yl]-2,4-pyrimidinediamine as a white solid. 1H NMR (acetone-d6): δ 2.68 (t, J=7.2 Hz, 2H), 3.71 (t, J=7.2 Hz, 2H), 4.62 (t, J=1.2 Hz, 2H), 6.42 (ddd, J=1.2 and 2.4 and 7.5 Hz, 1H), 6.98-7.08 (m, 3H), 7.38 (t, J=2.4 Hz, 1H), 7.62 (dd, J=2.4 and 8.7 Hz, 1H), 7.96 (d, J=3.3 Hz, 1H), 8.12 (s, 1H), 8.16 (s, 1H), 8.52 (d, J=2.7 Hz, 1H), 8.65 (s, 1H); 19F NMR (282 MHz, acetone-d6): δ−168.04.

Sources & evidence

ORD record
ord-40c2c779d9d84c559c6f6b89105caf1b
Source dataset
uspto-grants-2014_09
Patent number
US08822685B2

Linked notes

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