Ethylenediamine → HCID 10169029, compound

HRID 586746Notes

Reaction equation

HRID 586746 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](O)=[O:43])[S:7][C:6]=2[CH:45]=1.CN(C(O[N:54]1N=[N:61][C:56]2C=CC=C[C:55]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C(N)CN>CN(C=O)C>[NH2:54][CH2:55][CH2:56][NH:61][C:42]([C:8]1[S:7][C:6]2[CH:45]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[C:9]=1[CH:10]1[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][N:19]2[C:27]3[CH2:26][CH2:25][N:24]([S:28]([CH3:31])(=[O:29])=[O:30])[CH2:23][C:22]=3[C:21]([C:32]3[CH:33]=[CH:34][C:35]([C:38]([F:40])([F:39])[F:41])=[CH:36][CH:37]=3)=[N:20]2)[CH2:14][CH2:15]1)=[O:43]

Participants

6

Reactant 4

HCID 3301EthylenediamineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22311998HCID 22311998, compound

Product 1

HCID 10169029HCID 10169029, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 300 mg (0.43 mmol) 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 5 mL of dry DMF was treated with 812 mg (2.14 mmol) of HBTU and 0.75 mL (4.28 mmol) of DIEA. The solution was stirred for 5 min before the addition of 0.28 mL (4.28 mmol) of ethylenediamine. The reaction was stirred at room temperature for 30 min then partitioned between EtOAc (30 mL) and saturated sodium bicarbonate (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 200 mg (66%) of a clear oil. MS (electrospray): exact mass calculated for C33H38F4N6O3S2: 706.24; m/z found, 707.2 [M+H]+. 1H NMR (CD3OD, 400 MHz): 8.14 (m, 1H), 7.84 and 7.72 (A and B of AB quartet, J=8.41 Hz, 4H), 7.68 (m, 1H), 7.21 (dt, J=8.81, 2.74 Hz, 1H), 4.54 (s, 2H), 4.27 (t, J=6.26 Hz, 2H), 4.00-3.90 (m, 2H), 3.76-3.61 (m, 8H), 3.28-3.23 (br m, 1H), 3.19-3.09 (br m, 3H), 2.98 (s, 3H), 2.97-2.93 (m, 2H), 2.67 (br m, 2H), 2.52-2.37 (m, 3H), 2.02 (br d, J=13.89 Hz, 2H).

Workup

  1. customthen partitioned between EtOAc (30 mL) and saturated sodium bicarbonate (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-858bcc64cb384b1ba38ca48d8295e476
Source dataset
uspto-grants-2005_08
Patent number
US06936603B2

Reaction notes

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