Diisopropylethylamine → HCID 136216310, compound

HRID 1748774Notes

Reaction equation

HRID 1748774 reaction equation
[CH2:1]([N:3]1[C:7]2[NH:8][CH2:9][CH2:10][S:11][CH:12]([C:13]3[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][C:14]=3[CH3:22])[C:6]=2[C:5]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)=[N:4]1)[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:62][N:63]1[C:67]([NH2:68])=[CH:66][CH:65]=[N:64]1>CN(C=O)C>[CH2:1]([N:3]1[C:7]2[NH:8][CH2:9][CH2:10][S:11][CH:12]([C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH:68][C:67]4[N:63]([CH3:62])[N:64]=[CH:65][CH:66]=4)=[O:19])=[CH:15][C:14]=3[CH3:22])[C:6]=2[C:5]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)=[N:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1369272-Methyl-2H-pyrazol-3-ylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 136348443HCID 136348443, compound

Product 1

HCID 136216310HCID 136216310, compoundYield 42.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzoic acid (0.60 g, 1.521 mmol, Preparation # V.1) and DIEA (0.80 mL, 4.56 mmol), in DMF was added HATU (0.64 g, 1.67 mmol). The reaction mixture was stirred for about 30 min and 1-methyl-1H-pyrazol-5-amine (0.22 g, 2.28 mmol, Aldrich) was added. The reaction mixture stirred for about 5 h and was concentrated under reduced pressure. The residue was dissolved in DCM (15 mL) and washed with saturated NaHCO3 (5 mL). The organic layer was separated and dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by RP-HPLC (Table 2, Method e), to afford 4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(1-methyl-1H-pyrazol-5-yl)benzamide (0.30 g, 0.64 mmol, 42%) as a white solid. LC-MS (Table 1, Method g) Rt=2.01 min, m/z 474 (M+H)+; 1H NMR (DMSO-d6) δ 10.11 (s, 1H), 8.52-8.48 (m, 1H), 7.87-7.81 (m, 1H), 7.76-7.70 (m, 2H), 7.62 (dd, J=8.1, 1.8 Hz, 1H), 7.36 (d, J=1.9 Hz, 1H), 7.33 (d, J=8.1 Hz, 1H), 7.24-7.18 (m, 1H), 6.89 (s, 1H), 6.19 (d, J=1.9 Hz, 1H), 5.83 (d, J=4.6 Hz, 1H), 4.31-4.00 (m, 2H), 3.76-3.68 (m, 1H), 3.65 (s, 3H), 3.06-2.95 (m, 1H), 2.77-2.62 (m, 2H), 2.60 (s, 3H), 1.34 (t, J=7.1 Hz, 3H).

Workup

  1. stirringThe reaction mixture stirred for about 5 h
  2. concentrationwas concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in DCM (15 mL)
  4. washwashed with saturated NaHCO3 (5 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by RP-HPLC (Table 2, Method e)

Sources & evidence

ORD record
ord-282df817a46b4aed86435fb0e6d7c89a
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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