Sodium Carbonate → HCID 25195720, compound

HRID 2067889Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:24]=[CH:23][C:12]([CH2:13][N:14]3[CH2:19][CH2:18][CH:17]([C:20]([OH:22])=[O:21])[CH2:16][CH2:15]3)=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[F:25][CH:26]([F:43])[O:27][C:28]1[CH:33]=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][CH:29]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:25][CH:26]([F:43])[O:27][C:28]1[CH:33]=[CH:32][C:31]([C:2]2[CH:3]=[N:4][C:5]([NH:8][C:9]3[CH:24]=[CH:23][C:12]([CH2:13][N:14]4[CH2:19][CH2:18][CH:17]([C:20]([OH:22])=[O:21])[CH2:16][CH2:15]4)=[CH:11][CH:10]=3)=[N:6][CH:7]=2)=[CH:30][CH:29]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of 1-(4-(5-bromopyrimidin-2-ylamino)benzyl)piperidine-4-carboxylic acid 17 (0.05 mmol) in 1,4-dioxane (1.0 mL) is added 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 7 (0.05 mmol), 3M Na2CO3 (0.15 mmol) and Pd(PPh3)4 (0.0025 mmol). The reaction is evacuated and backfilled with nitrogen twice then heated at 150° C. for 10 min. Purification by preparative HPLC (ACN gradient 10-70%) affords 1-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)benzyl)piperidine-4-carboxylic acid A4. 1H NMR (400 MHz, d4-MeOH) δ 8.64 (s, 2H), 7.78 (d, J=8.8 Hz, 2H), 7.56 (d, J=8.8 Hz, 2H), 7.32 (d, J=8.8 Hz, 2H), 7.16 (d, J=8.8 Hz, 2H), 6.78 (t, J=74.0 Hz, 1H), 4.11 (s, 2H), 3.31 (m, 2H), 2.92 (m, 2H), 2.36 (m, 1H), 2.02 (m, 2H), 1.81 (m, 2H). MS (m/z) (M+1)+: 455.2.

Workup

customThe reaction is evacuated
customPurification by preparative HPLC (ACN gradient 10-70%)

Sources & evidence

ORD record: ord-f8041aa1971a48fc859c4f19fa9e2163
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293757B2

Reaction notes

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