Diisopropylethylamine → HCID 10284032, compound

HRID 1370060Notes

Reaction equation

HRID 1370060 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([CH:10]3[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][N:19]4[C:27]5[CH2:26][CH2:25][N:24]([S:28]([CH3:31])(=[O:30])=[O:29])[CH2:23][C:22]=5[C:21]([C:32]5[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=5)=[N:20]4)[CH2:12][CH2:11]3)=[C:8]([C:42]([OH:44])=O)[S:7][C:6]=2[CH:45]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:79][CH2:80][CH2:81][N:82]1[CH2:87][CH2:86][O:85][CH2:84][CH2:83]1>CN(C=O)C>[N:82]1([CH2:81][CH2:80][NH:79][C:42]([C:8]2[S:7][C:6]3[CH:45]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[C:9]=2[CH:10]2[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][N:19]3[C:27]4[CH2:26][CH2:25][N:24]([S:28]([CH3:31])(=[O:29])=[O:30])[CH2:23][C:22]=4[C:21]([C:32]4[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:39])[F:40])=[CH:34][CH:33]=4)=[N:20]3)[CH2:14][CH2:15]2)=[O:44])[CH2:87][CH2:86][O:85][CH2:84][CH2:83]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 4082852-MorpholinoethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22311998HCID 22311998, compound

Product 1

HCID 10284032HCID 10284032, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 20 mg (0.03 mmol) of 6-fluoro-3-(1-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl )-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin -1-yl]-propyl}-piperidin-4-yl)-benzo[b]thiophene-2-carboxylic acid in 0.3 mL of dry DMF was treated with 14 mg (0.036 mmol) of HBTU and 8 μL (0.045 mmol) of DIEA. The solution was stirred for 5 min before the addition of 20 μL (0.15 mmol) of 4-(2-aminoethyl)morpholine. The reaction was stirred at room temperature for 30 min then partitioned between EtOAc (30 mL) and saturated NaHCO3 (20 mL). The aqueous layer was further extracted with EtOAc (2×20 mL). The combined organic layers were then washed with brine, dried over Na2SO4, and concentrated. Purification by column chromatography (silica, 5-10% of (2 N NH3 in MeOH)/CH2Cl2) afforded 15 mg (65%) of a white solid. MS (electrospray), exact mass calculated for C37H44F4N6O4S2: 776.28; m/z found, 777.3 [M+H]+. 1H NMR (CDCl3, 400 MHz): 8.07 (br s, 1H), 7.73 and 7.66 (A and B of AB quartet, J=8.41 Hz, 4H), 7.50 (dd, J=8.41, 2.35 Hz, 1H), 7.14 (dt, J=8.61, 2.54 Hz, 1H), 6.64 (t, J=4.70 Hz, 1H), 4.56 (s, 2H), 4.16 (t, J=6.85 Hz, 2H), 3.80-3.67 (m, 7H), 3.53 (q, J=5.48 Hz, 2H), 3.03 (br m, 2H), 2.98 (t, J=5.67 Hz, 2H), 2.90 (s, 3H), 2.60 (t, J5.87 Hz, 2H), 2.38 (br m, 4H), 2.12 (br m, 4H), 1.86-1.73 (br m, 3H).

Workup

  1. customthen partitioned between EtOAc (30 mL) and saturated NaHCO3 (20 mL)
  2. extractionThe aqueous layer was further extracted with EtOAc (2×20 mL)
  3. washThe combined organic layers were then washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customPurification by column chromatography (silica, 5-10% of (2 N NH3 in MeOH)/CH2Cl2)

Sources & evidence

ORD record
ord-d8c865ff4eef4cb0856056d5460fa2a3
Source dataset
uspto-grants-2003_06
Patent number
US06579896B2

Reaction notes

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