Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → HCID 70980768, compound

HRID 1409376Notes

Reaction equation

HRID 1409376 reaction equation
[C:1]([N:20]1[CH:24]=[C:23]([C:25]2[CH:29]=[C:28]([C:30](O)=[O:31])[NH:27][N:26]=2)[N:22]=[CH:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:33][C@@H:34]([CH3:51])[CH2:35][N:36]1[CH:40]=[CH:39][C:38]([C:41]2[CH:48]=[C:47]([F:49])[C:44]([C:45]#[N:46])=[C:43]([Cl:50])[CH:42]=2)=[N:37]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Cl:50][C:43]1[CH:42]=[C:41]([C:38]2[CH:39]=[CH:40][N:36]([CH2:35][C@@H:34]([NH:33][C:30]([C:28]3[NH:27][N:26]=[C:25]([C:23]4[N:22]=[CH:21][N:20]([C:1]([C:8]5[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=5)([C:14]5[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=5)[C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)[CH:24]=4)[CH:29]=3)=[O:31])[CH3:51])[N:37]=2)[CH:48]=[C:47]([F:49])[C:44]=1[C:45]#[N:46]

Participants

5

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67170587(S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrileHCID 70982355HCID 70982355, compound

Product 1

HCID 70980768HCID 70980768, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The title compound was prepared using the procedure described in Example 3(h) starting from 3-(1-trityl-1H-imidazol-4-yl)-1H-pyrazole-5-carboxylic acid (0.875 mmol, 0.368 g) and (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile (0.673 mmol, 0.250 g) using HBTU (0.067 mmol, 0.026 g) instead of HOBt. DCM (4 ml) was used as the solvent. The reaction mixture was diluted with DCM and washed with 1 M Na2CO3 and water. The separated organic phase was dried, filtered and evaporated to give 0.511 g of crude product. Another crude batch (931 mg) was combined here and purified first by trituration in ACN and then by flash chromatography to give 0.095 g of the product. 1H-NMR (400 MHz, DMSO-d6): δ 1.18 (d, 3H), 4.13-4.53 (m, 3H), 6.64 (s, 1H), 6.98 (d, 1H), 7.09-7.19 (m, 4H), 7.35-7.51 (m, 9H), 7.52-7.57 (m, 1H), 7.70-7.76 (m, 1H), 7.79-7.86 (m, 2H), 7.92 (s, 1H), 7.95 (s, 1H), 8.06-8.10 (m, 1H), 8.14-8.18 (m, 1H), 13.35 (bs, 1H).

Workup

  1. washwashed with 1 M Na2CO3 and water
  2. customThe separated organic phase was dried
  3. filtrationfiltered
  4. customevaporated
  5. customto give 0.511 g of crude product

Sources & evidence

ORD record
ord-e4f39037758a4a69a82ef61b7f2a8faa
Source dataset
uspto-grants-2014_12
Patent number
US08921378B2

Reaction notes

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