Diisopropylethylamine → 3-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-5-fluoro-N-(3-hydroxycyclobutyl)benzamide

HRID 1049894Notes

Reaction equation

HRID 1049894 reaction equation
[NH2:1][C:2]1[C:3]2[N:11]=[C:10]([C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([F:21])[CH:20]=3)[C:15]([OH:17])=O)[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.N[CH:23]1[CH2:26][CH2:25][CH:24]1[OH:27].C[N:29](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:1][C:2]1[C:3]2[N:11]=[C:10]([C:12]3[CH:13]=[C:14]([CH:18]=[C:19]([F:21])[CH:20]=3)[C:15]([NH:29][CH:26]3[CH2:25][CH:24]([OH:27])[CH2:23]3)=[O:17])[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 124142992-Aminocyclobutan-1-olHCID 727035203-(4-Aminopyrido[3,2-d]pyrimidin-6-yl)-5-fluorobenzoic acid

Product 1

HCID 727035223-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-5-fluoro-N-(3-hydroxycyclobutyl)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Following the same reaction and purification procedure, the acid 3 (50 mg, 0.17 mmol) was reacted with 2-aminocyclobutanol (CAS 4640-44-2) (30 mg, 0.35 mmol), HATU (135 mg, 0.35 mmol) and DIPEA (0.15 mL, 0.9 mmol) in DMF (1 mL) at room temperature to provide 3-(4-aminopyrido[3,2-d]pyrimidin-6-yl)-5-fluoro-N-(3-hydroxycyclobutyl)benzamide 8 as a mixture of cis and trans isomer. LC/MS (ESI+): m/z 354 (M+H). 1H NMR (400 MHz, DMSO) δ 8.81 (d, J=6.9 Hz, 1H), 8.63 (d, J=10.2 Hz, 1H), 8.54 (dd, J=10.1, 8.9 Hz, 3H), 8.44 (s, 1H), 8.31 (s, 1H), 8.20 (d, J=8.8 Hz, 1H), 8.03 (s, 1H), 7.73 (d, J=8.2 Hz, 2H), 5.15 (d, J=5.4 Hz, 1H), 5.05 (d, J=5.2 Hz, 1H), 4.48 (d, J=6.2 Hz, 1H), 4.37 (d, J=4.7 Hz, 1H), 4.04-3.84 (m, 2H), 2.96-2.84 (m, 1H), 2.69-2.54 (m, 2H), 2.39-2.28 (m, 1H), 2.21 (ddd, J=12.6, 8.1, 4.7 Hz, 1H), 1.97 (ddd, J=17.2, 8.7, 2.7 Hz, 2H).

Workup

  1. customthe same reaction and purification procedure

Sources & evidence

ORD record
ord-ae6a57eac30247c590273823f89edef7
Source dataset
uspto-grants-2016_07
Patent number
US09382241B2

Reaction notes

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