Diisopropylethylamine → HCID 117868325, compound

HRID 877848Notes

Reaction equation

HRID 877848 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.Br.[CH2:35]1[C:38]2([CH:42]([NH:43][C:44]3[C:45]4[N:46]([CH:53]=[C:54]([C:56]5[CH:57]=[N:58][N:59]([CH3:61])[CH:60]=5)[CH:55]=4)[N:47]=[CH:48][C:49]=3[C:50]([NH2:52])=[O:51])[CH2:41][NH:40][CH2:39]2)[CH2:37][CH2:36]1.[CH:62]1([C:65]([O-])=[O:66])[CH2:64][CH2:63]1>CN(C=O)C>[CH:62]1([C:65]([N:40]2[CH2:41][C@@H:42]([NH:43][C:44]3[C:45]4[N:46]([CH:53]=[C:54]([C:56]5[CH:57]=[N:58][N:59]([CH3:61])[CH:60]=5)[CH:55]=4)[N:47]=[CH:48][C:49]=3[C:50]([NH2:52])=[O:51])[C:38]3([CH2:37][CH2:36][CH2:35]3)[CH2:39]2)=[O:66])[CH2:64][CH2:63]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 6992810Cyclopropanecarboxylic acid, ion(1-)HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 131732608HCID 131732608, compound

Product 1

HCID 117868325HCID 117868325, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 200 uL aliquot of HATU (23.41 mg, 0.062 mmol) and diisopropylethylamine (21.51 μl, 0.123 mmol) were added to a 200 uL aliquot of 4-(6-azaspiro[3.4]octan-8-ylamino)-6-(1-methyl-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide HBr (from Step 6, 15 mg, 0.041 mmol) and cyclopropane carboxylate (1.5 equiv.) in DMF. The reaction was stirred for 3 h at room temperature. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 0-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to afford the title compound (3.9 mg). 1H NMR (500 MHz, METHANOL-d4/CDCl3) δ 8.11 (d, J=11.9 Hz, 1H), 7.80 (d, J=9.9 Hz, 1H), 7.78-7.71 (m, 2H), 6.91 (dd, J=14.1, 1.7 Hz, 1H), 4.83-4.75 (m, 1H), 4.13 (dd, J=10.4, 5.0 Hz, 1H), 4.07-3.99 (m, 1H), 3.96 (s, 1.5H), 3.94 (s, 1.5H), 3.98-3.76 (m, 2H), 2.37 (dd, J=11.1, 7.2 Hz, 1H), 2.28-1.95 (m, 5H), 1.12-0.70 (m, 4H)

Workup

  1. customThe crude material was purified via preparative LC/MS with the following conditions
  2. waitGradient: 0-100% B over 25 minutes
  3. customa 5-minute hold
  4. additionFractions containing the desired product
  5. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-f27a2363a01c45458d5f56a3fe1709a0
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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