Diisopropylethylamine → HCID 90341266, compound

HRID 1485661Notes

Reaction equation

HRID 1485661 reaction equation
[Br:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:35]=[CH:34][C:9]([CH2:10][NH:11][C:12]2[N:17]=[C:16]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])[N:15]=[C:14]([NH:24][C:25]3[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=3)[N:13]=2)=[CH:8][C:7]=1[Cl:36].C(N(CC)C(C)C)(C)C.[C:46]([O:50][C:51](=[O:59])[NH:52][CH2:53][C:54]([CH3:58])([CH3:57])[CH2:55][NH2:56])([CH3:49])([CH3:48])[CH3:47].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[C:46]([O:50][C:51](=[O:59])[NH:52][CH2:53][C:54]([CH3:58])([CH3:57])[CH2:55][NH:56][C:29](=[O:30])[C:28]1[CH:27]=[CH:26][C:25]([NH:24][C:14]2[N:13]=[C:12]([NH:11][CH2:10][C:9]3[CH:34]=[CH:35][C:6]([O:5][CH2:4][CH2:3][CH2:2][Br:1])=[C:7]([Cl:36])[CH:8]=3)[N:17]=[C:16]([O:18][CH2:19][C:20]([F:23])([F:21])[F:22])[N:15]=2)=[CH:33][CH:32]=1)([CH3:49])([CH3:47])[CH3:48]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 4114359tert-butyl N-(3-amino-2,2-dimethylpropyl)carbamateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 90101837HCID 90101837, compound

Product 1

HCID 90341266HCID 90341266, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 100 mL round-bottom flask charged with the 4-((4-((4-(3-bromopropoxy)-3-chlorobenzyl)amino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl)amino)benzoic acid prepared above (13.0 mmol) was added CH2Cl2 (65 mL), and then N,N-diisopropylethylamine (7.95 mL, 45.5 mmol). The flask was cooled with a 0° C. bath. To the solution was added tert-butyl(3-amino-2,2-dimethylpropyl)carbamate (3.16 g, 15.6 mmol), and then 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 6.43 g, 16.9 mmol). The bath was removed and the solution was allowed to warm to room temperature with stirring for 1 h. The solution was transferred to a 1 L separatory funnel and was diluted with EtOAc (500 mL). The solution was washed with aq. 2M HCl (2×100 mL), and then with sat. aq. NaHCO3 (100 mL), and then with sat. aq. NaCl (100 mL). The organic solution was dried over MgSO4; filtered; and then concentrated in vacuo. The resulting solid residue was subjected to SiO2 chromatography (hexanes:EtOAc, 1:1) to afford tert-butyl(3-(4-((4-((4-(3-bromopropoxy)-3-chlorobenzyl)amino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-yl)amino)benzamido)-2,2-dimethylpropyl)carbamate as a colorless solid (8.77 g, 81%). 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J=8.5 Hz, 2H), 7.76-7.66 (m, 1H), 7.62 (dd, J=15.6, 8.5 Hz, 2H), 7.35 (s, 1H), 7.22-7.15 (m, 1H), 6.96-6.89 (m, 1H), 5.16-5.04 (m, 1H), 4.73 (dq, J=12.2, 8.4 Hz, 2H), 4.57 (d, J=5.3 Hz, 2H), 4.19-4.14 (m, 2H), 3.69-3.61 (m, 2H), 3.28-3.18 (m, 2H), 3.00-2.92 (m, 2H), 2.36 (sxt, J=5.8 Hz, 2H), 1.46 (d, J=2.0 Hz, 9H), 0.91 (d, J=3.3 Hz, 6H); MS m/z=774.25 (M+1)+.

Workup

  1. customprepared above (13.0 mmol)
  2. customThe bath was removed
  3. temperatureto warm to room temperature
  4. customThe solution was transferred to a 1 L separatory funnel
  5. additionwas diluted with EtOAc (500 mL)
  6. washThe solution was washed with aq. 2M HCl (2×100 mL)
  7. dry with materialThe organic solution was dried over MgSO4
  8. filtrationfiltered
  9. concentrationand then concentrated in vacuo

Sources & evidence

ORD record
ord-8afef3f0bc3a43a581dbe3fd0fae9ce2
Source dataset
uspto-grants-2016_08
Patent number
US09422311B2

Reaction notes

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